Discovering missing heritability and early risk prediction for

Turkish Journal of Medical Sciences
Turk J Med Sci
(2014) 44: 946-954
© TÜBİTAK
doi:10.3906/sag-1310-77
http://journals.tubitak.gov.tr/medical/
Research Article
Discovering missing heritability and early risk prediction for type 2 diabetes: a new
perspective for genome-wide association study analysis with the Nurses’ Health Study
and the Health Professionals’ Follow-Up Study
1,
2
3
Hüsamettin GÜL *, Yeşim AYDIN SON , Cengizhan AÇIKEL
Department of Medical Informatics, Gülhane Military Medical Academy, Etlik, Ankara, Turkey
2
Department of Health Informatics, Informatics Institute, Middle East Technical University, Ankara, Turkey
3
Department of Biostatistics, Gülhane Military Medical Academy, Etlik, Ankara, Turkey
1
Received: 21.10.2013
Accepted: 03.01.2014
Published Online: 24.10.2014
Printed: 21.11.2014
Background/aim: Despite the rise in type 2 diabetes prevalence worldwide, we do not have a method for early risk prediction. The
predictive ability of genetic models has been found to be little or negligible so far. In this study, we aimed to develop a better early risk
prediction method for type 2 diabetes.
Materials and methods: We used phenotypic and genotypic data from the Nurses’ Health Study and Health Professionals’ Follow-up
Study cohorts and analyzed them by using binary logistic regression.
Results: Phenotypic variables yielded 70.7% overall correctness and an area under the curve (AUC) of 0.77. With regard to genotype,
798 single nucleotide polymorphisms with P-values of lower than 1.0E-3 yielded 90.0% correctness and an AUC of 0.965. This is the
highest score in the literature, even including the scores obtained with phenotypic variables. The additive contributions of phenotype
and genotype increased the overall correctness to 92.9% and the AUC to 0.980.
Conclusion: Our results showed that genotype could be used to obtain a higher score, which could enable early risk prediction. These
findings present new possibilities for genome-wide association study analysis in terms of discovering missing heritability. These results
should be confirmed by follow-up studies.
Key words: Type 2 diabetes, genome-wide association study, single nucleotide polymorphism, Affymetrix, binary logistic regression,
ROC curve
1. Introduction
Type 2 diabetes is a complex disease that is characterized
by insulin resistance in peripheral tissues and dysfunction
in insulin secretion. Type 2 diabetes is a major public
health problem, and its prevalence is increasing at an
alarming rate worldwide. It has been estimated that 371
million people are already affected by type 2 diabetes, and
the number is projected to reach 552 million by 2030 (1).
The development of type 2 diabetes is caused by a
combination of lifestyle and genetic factors (2,3). Some
risk factors, such as diet and obesity, are under personal
control; however, genetic factors are not (4). Although the
rise in type 2 diabetes prevalence can be mostly attributed
to changes in diet and lifestyle, there is strong evidence of a
genetic basis for type 2 diabetes (2). However, genetic risk
factors have been found to have lower predictive values
when compared to phenotype variables such as body
*Correspondence: hgul23@gmail.com
946
mass index (BMI), familial diabetes history (FAMDB),
high blood pressure (HBP), and cholesterol (CHOL)
(5,6). Furthermore, the additive contribution of genetic
studies using single nucleotide polymorphisms (SNPs)
to phenotype variables was found to be almost negligible
in several studies (5–12). Because numerous genetic and
nongenetic risk factors interact in the causation of type 2
diabetes, the predictive ability of genetic models will likely
remain modest.
At present, the clinical use of genetic testing for type
2 diabetes prediction in adults is not recommended (13).
Phenotypic risk factors have a higher predictive ability with
area under the curve (AUC) values of 0.70–0.90, but these
are in middle or later ages when the reversibility of factors
is low. Therefore, a model to predict the risk score for type
2 diabetes in the early stages is needed. Additionally, as
prediabetic individuals usually remain undiagnosed and
GÜL et al. / Turk J Med Sci
untreated, identifying new methods using the genotype
for the screening and prediction of risk factors is very
important. The early prediction of risk factors may help
patients to make lifestyle modifications in connection with
preventable risk factors, such as obesity (14).
Genome-wide association studies (GWASs) have
been widely used to investigate the role of the genotype
in the development of diseases. Although many studies
have been conducted to uncover the heritability of type
2 diabetes, only a small proportion of genetic heritability
can be explained by the variants identified. GWASs have
shown significant genome-wide associations with type 2
diabetes at 44 susceptibility loci so far (15). The current
type 2 diabetes risk variants explain only about 5%–10%
of the genetic basis of type 2 diabetes; much of the genetic
basis remains unexplained (16,17).
Most of these studies used logistic regression for the
analysis of genetic variables. However, the maximum
number of SNPs used was 42, and C-statistics results
(AUC) for the genotype were lower than 0.60 (5–12). In
the course of our GWAS analysis of Nurses’ Health Study
(NHS) and Health Professionals’ Follow-up Study (HPFS)
data, we realized that sensitivity, specificity, and C-statistics
increased with the number of SNPs. As we used genotype
data for the whole genome instead of a finite number of
SNPs, unlike previous studies, a high number of SNPs
were included in the analysis. The highest prediction risk
scores and AUCs for type 2 diabetes in the literature, even
when phenotype studies are included, were achieved in
this study using the 798 SNPs selected with P-values of
less than 1.0E-3 for the model. Our findings demonstrate
the importance of genotype in the prediction of type 2
diabetes, which has been previously disregarded.
2. Materials and methods
2.1. Study population
The NHS and HPFS are well-characterized cohorts of
nurses and health professionals, conducted in order to
identify novel genetic factors that contribute to type 2
diabetes through large-scale, GWASs and to investigate
the role of environmental exposure on the development
of type 2 diabetes. The NHS and HPFS cohorts are part
of the Gene Environment Association Studies initiative
(GENEVA, http://www.genevastudy.org). The NHS was
established in 1976, and the HPFS study was started in
1986. Participants of the NHS and HPFS completed a
mailed questionnaire on their medical history and lifestyle.
Blood was collected in 1989–1990 for the NHS and in
1993–1995 for the HPFS. Genotyping was completed in
December 2008 for the NHS and in March 2009 for the
HPFS. Lifestyle factors, including smoking, menopausal
status and postmenopausal hormone therapy, and body
weight, have been updated by validated questionnaires
every 2 years.
Participants meeting the following criteria were
excluded from the study: 1) those with other types of
diabetes (65 NHS, 68 HPFS); 2) those belonging to races
other than white (61 NHS, 100 HPFS); 3) HapMap controls
(45 NHS, 29 HPFS); and 4) first-degree relatives (15 NHS,
14 HPFS). The final sample included 3248 (1769 controls
and 1479 cases) for the NHS and 2391 (1277 controls and
1114 cases) for the HPFS. The current analysis includes
SNPs mapped to chromosomes 1 through 23, as annotated
based on the Affymetrix Genome-Wide Human SNP
Array 6.0 (GeneChip 6.0).
2.2. Phenotypic variables
BMI has been shown to be the most important phenotypic
variable in risk prediction of type 2 diabetes. BMI data were
continuous in our study, and we converted them to binary
using threshold levels that were calculated separately for
males and females using the Youden Index (YI = sensitivity
+ specificity – 1) against the status of diabetes. We found
BMI threshold levels of 26.3 kg/m2 for females and 27.1
kg/m2 for males that maximized the YI. Other phenotypic
data including FAMDB, CHOL, and HBP were binary.
We also analyzed other phenotypic variables. While
sex, polyunsaturated fat intake, trans fat intake, and
magnesium intake were statistically not important,
smoking, activity levels, postmenopausal hormonal status,
alcohol, cereal fiber intake, heme iron intake, and glycemic
load were found to be significantly related to diabetic status
(data not shown). However, since these variables mostly
depend on individual declaration, they are subjective. The
contribution of these variables to classification and the
AUC were negligible; therefore, we excluded them from
the analysis for clarity.
2.3. Software
Analyses were conducted using PLINK and SPSS 15.0
for Windows. Amelia software was used to fill in missing
values, and R was used for graphical presentation of
quantile plots and Manhattan plots (www.r-project.org).
PLINK version 1.07 was used to analyze genome-wide
data (http://pngu.mgh.harvard.edu/~purcell/plink). We
merged NHS and HPFS data first. SNPs that met any of
the following criteria were excluded from the analysis: 1)
minor allele frequencies (MAF) of <0.05; 2) call rate of
<95%; 3) P for Hardy–Weinberg equilibrium of <0.001;
and 4) missing rates 0.1. After applying the QC filter,
642,576 SNPs remained for the analyses.
2.4. Binary logistic regression
We performed binary logistic regression (BLR) using
NHS and HPFS genotypic and phenotypic data via SPSS
to test the associations of the genotypic and phenotypic
risk scores with diabetes. We coded genotypes for
common allele homozygotes, heterozygotes, and rare allele
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GÜL et al. / Turk J Med Sci
3. Results
3.1. The clinical characteristics of the participants
The clinical characteristics of the study populations are
presented in Table 1. We performed a genome-wide
analysis of NHS and HPFS participants. The frequency
distribution of the P-value of the SNPs is given in Table
2. The P-values of 886 SNPs were less than 1.0E-03. The
distribution of P-values for all SNPs (642,576) versus
chromosomal distribution is shown as a Manhattan plot
in Figure 1. Chromosomes, P-values, odds ratios, and
MAF values of 798 SNPs are provided in the Appendix
(on the journal’s website). Quantile–quantile (QQ) plots
of P-values of SNPs are given against the expected P-values
in Figure 2. We accepted 1.0E-3 as the threshold level to
determine which SNPs would be included in the analysis
(Figure 2). Initially, 886 SNPs were considered; after a
quality check for missing criteria, 798 SNPs were used.
3.2. BLR analysis of phenotype
The analysis results of phenotype variables of the NHS
and HPFS data sets are presented in Table 2. The summary
of BMI is also listed in Table 3 as a continuous variable.
As noted in Section 2, BMI was converted to a binary
form before BLR analysis. Type 2 diabetes patients had
significantly higher BMIs than the controls. BMI was
strongly associated with type 2 diabetes; the odds ratio for
Table 1. Clinical characteristics of the participants. Data
presented as mean ± SD.
Type 2 diabetes
Control subjects
n (male/female)
1114/1479
1277/1769
Age (years)
57.42 ± 7.72
57.12 ± 7.66
Female
29.91 ± 5.76
25.39 ± 4.83
Male
27.89 ± 4.14
25.21 ± 2.82
BMI (kg/m2)
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Table 2. P-value distribution of SNPs (before filtering of missing
alleles, see Section 2).
P-value
Cumulative frequency
Frequency
<1.0E-11
1
1
1.0E-10
6
5
1.0E-09
6
0
1.0E-08
6
0
1.0E-07
10
4
1.0E-06
29
19
1.0E-05
132
103
1.0E-04
886
754
BMI was 3.86. Other important phenotypes were FAMDB,
HBP, and CHOL. Their P-values and odds ratios are also
given in Table 4. The combined effect of these 4 phenotype
variables yielded an overall classification of 70.7% and an
AUC of 0.77. We also compared rs10739592, which had
the lowest P-value in GWAS analysis, with phenotypic
variables. It should be noted that rs10739592 alone (OR:
1.34, P-value: 2.08E-14) increased the overall prediction by
only 2.84%. The composite effect of phenotypic variables
was less than the sum of the individual effects of each
variable alone due to the effect of overlap.
We were able to predict individual risk scores using the
following formula with constants obtained from logistic
regression analyses of familial diabetes history, high blood
pressure, cholesterol, and BMI.
14
12
10
–log10 (ρ)
homozygotes separately for analysis. We evaluated model
discrimination by using C-statistics (areas under receiver
operating characteristic curves, ROC-AUCs), which were
calculated for the predicted risk of the logistic regression
model.
We used SNPs with P-values of less than 1.0E-3. There
were 886 SNPs with P-values below this level. However,
we excluded SNPs if the missing allele number was greater
than 50 (patients), except for rs10739592, since it had the
lowest P-value (2.08E-14). It had 99 missing alleles. To
fill in the missing alleles, we used the Amelia toolbox for
imputation (18). The result of the imputation was validated
by comparing ‘before’ and ‘after’ P-values of SNPs and
observing the relative distribution density of the original
data set and the imputed data set.
8
6
4
2
0
1
2
3
4
5 6
8 10 12
Chromosome
14
17
21
Figure 1. Manhattan plot of the point-wise P-values for the
642,576 SNP loci of the NHS and HPFS data sets.
GÜL et al. / Turk J Med Sci
14
12
Observed –log10 (ρ)
10
8
6
4
2
0
0
1
2
3
4
Expected –log10 (ρ)
5
6
Figure 2. Quantile-quantile plots of SNP P-values in (NHS+HPFS)
GWAS analysis. The x-axis is –log10 of the expected P-values and
the y-axis is –log10 of the observed P-values. Detaching point
from the expected –log10 is nearly 1.0E-3.
P=
exp(-1,579+famdb+1,132+hbp×0,862+chol×0,556+BMI×1,351
1+exp(-1,579+famdb+1,132+hbp×0,862+chol×0,556+BMI×1,351
The C-statistics (AUC) value for the 4 phenotype
variables was found to be 0.77 ± 0.003.
3.3. BLR analysis of genotype
Because the number of SNPs (798) is high and is unusual
for BLR, as reported in the literature, we used a different
approach to evaluate the effect of genotype on prediction
scores and AUC. First, we grouped SNPs according to their
P-values. Three groups of SNPs with P-values of less than
1.0E-4 yielded a maximum prediction score of 67.4% and
an AUC of 0.735; 680 SNPs with P-values between 1.0E04 and 1.0E-03 yielded a prediction score of 87.7% and an
AUC of 0.947. When we used an incremental approach,
the first 3 groups containing 118 SNPs with P-values of less
than 1.0E-4 yielded prediction scores that were lower than
that of the fourth group (Table 5). This showed that more
SNPs should be included for higher prediction rates and
explained why previous studies in the literature that used
a maximum of 40 SNPs obtained lower predictive values.
In addition, we tested how various threshold levels in BLR
analysis affected the prediction score and AUC (Table
6). The threshold level was chosen to be 0.5 by default in
BLR analysis. When the threshold level increases, negative
predictive value increases, positive predictive value
decreases, and AUC does not change (Table 6).
We also investigated the additive contribution of
phenotypes to the model built from genotyping data. The
addition of 4 phenotypes (BMI, FAMDB, CHOL, and
HBP) increased the prediction score from 90.0% to 92.9%
and the AUC from 0.965 to 0.980 (Figure 3).
In addition, we found important differences between
females and males in SNPs corresponding to the
transcription factor-7–like 2 (TCF7L2) gene (Table 7). We
found that the TCF7L2 gene was more determinative in
males than in females. Although the TCF7L2 gene is one
of the most significant genetic marker associated with type
2 diabetes mellitus risk (19), there is no information in
the literature about the relationship between the TCF7L2
gene and sex. This finding is important when interpreting
literature on interethnic differences that do not mention
sex.
4. Discussion
Development of genotype-based prediction will help us in
the early prediction, identification, and prevention of type
2 diabetes. We showed that genotype-based predictions for
type 2 diabetes yielded as high a score as phenotype-based
methods. We obtained 90.0% prediction correctness, and
the AUC was 0.965 with only genotype (SNP) variables.
According to our knowledge, this is the highest score
reported in the literature for risk prediction of type 2
diabetes.
GWAS has facilitated the understanding of the genetic
basis of complex traits; it is a powerful method for the
detection of genetic variations that predispose individuals
Table 3. Body mass index values of males and females in the control and diabetic groups. Data presented as
mean ± SD.
Male
n
Female
n
Average
n
Control
25.21 ± 2.82
1277
25.39 ± 4.83
1769
25.31 ± 4.11
3046
Diabetes
27.89 ± 4.14a
1114
29.91 ± 5.76b
1479
29.04 ± 5.22c
2593
Average
26.45 ± 3.74
2391
27.44 ± 5.73
3248
27.03 ± 5.01
5639
Independent sample t-test, 3.72E-115.
Independent sample t-test, 1.52E-68.
c
Independent sample t-test, 1.85E-174.
a
b
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GÜL et al. / Turk J Med Sci
Table 4. P-value, odds ratio, net reclassification improvement (NRI) percentage, overall prediction
percentage, and AUC of phenotypic variables (n/a, not applicable).
Phenotype
P-value
Odds ratio
NRI %
Overall
prediction %
AUC
Baseline
n/a
n/a
n/a
54
n/a
Body mass index
5.21E-108
3.86
13.99
68.0
0.68a
Familial diabetes history
4.32E-69
3.10
9.70
63.7
0.63b
High blood pressure
3.25E-39
2.37
9.68
63.7
0.62b
Cholesterol
7.76E-15
1.74
4.40
58.4
0.56
Four phenotypes
(BMI+FAMDB+HBP+CHOL)
1.56E-187
n/a
16.70
70.7
0.77c
rs10739592
2.08E-14
1.34
2.84
56.9
0.55
P < 0.001, significantly higher than other groups except BMI+FAMDB+HBP+CHOL.
P < 0.001, significantly higher than cholesterol and rs10739592.
c
P < 0.001, significantly higher than others.
BMI: Body mass index, FAMDB: familial diabetes history, HBP: high blood pressure, CHOL: cholesterol.
a
b
Table 5. Additive binary logistic regression analysis of SNPs grouped according to their P-values obtained in GWAS
analysis.
NPV: Negative predictive value, PPV: positive predictive value, AUC: area under curve.
SNP groups according
to their P-values
Number of SNPs (n)
NPV (percentage
correct for control)
PPV (percentage
correct for diabetes)
Overall % AUC
<1.0E-06
10
75.0
38.7
58.3
0.602
<1.0E-05
27 (10+17)
72.8
45.3
60.2
0.636
<1.0E-04
118 (91+27)
74.3
59.3
67.4
0.735
<1.0E-03
798 (680+118)
90.7
89.1
90.0
0.965
Table 6. Effects of cut-off value on classification correctness and AUC.
ROC cutoff value
SNPs (n)
NPV
PPV
Overall %
AUC
0.5
798
90.7
89.1
90.0
0.965 ± 0.002
0.6
798
94.0
83.7
89.3
0.965 ± 0.002
0.7
798
96.8
76.8
87.6
0.965 ± 0.002
0.8
798
98.4
67.5
84.2
0.965 ± 0.002
0.9
798
99.3
52.6
77.8
0.965 ± 0.002
NPV: Negative predictive value, PPV: positive predictive value, AUC: area under curve.
to complex chronic diseases. GWAS has provided many
useful insights into the pathophysiology of type 2 diabetes
by enabling the identification of novel susceptibility loci
that were not identified by classical approaches. However,
for most of the identified type 2 diabetes susceptibility loci,
the causal variants and molecular mechanisms for diabetes
risk are unknown. Our findings do not reject the importance
950
of susceptibility loci for causal variants, but rather provide
more accurate risk prediction. It is also important to
remember that the effect sizes found for SNPs thus far are
not a reflection of their biological or clinical significance.
Although their individual predictive values may be small,
SNPs as a profile might point to important biological
pathways that could be targeted for therapeutic intervention.
GÜL et al. / Turk J Med Sci
Table 7. SNPs corresponding to the TCF7L2 gene in our GWAS
analysis. The P-values of some SNPs differ between males and
females.
ROC Curve
1.0
Sensitivity
0.8
SNP
0.6
0.4
Phenotype
Genotype
0.2
Genotype+ Phenotype
0.0
0.0
0.2
0.4
0.6
Specificity
0.8
1.0
Figure 3. ROC plot for the BLR model containing type 2 diabetes
and 4 phenotype variants, body mass index, familial diabetes
history, high blood pressure, and cholesterol (black line, AUC
= 0.77), for the 798 SNP variants (red line, AUC = 0.965) and
genotype plus phenotype (blue line, AUC = 0.980).
Fortunately, the incidence of type 2 diabetes can be
delayed or prevented by maintaining healthy lifestyle
behaviors (14). The early identification of population
subgroups that are at particularly high risk for type 2
diabetes might facilitate the targeting of prevention efforts
to those who might benefit from them the most. Until
these findings, genetic associations have not appeared to
improve type 2 diabetes risk prediction, which has already
been achieved through clinical risk predictors alone.
In the time since the first GWAS data were published
in 2007 by the Wellcome Trust Case Control Consortium
(20), significant progress has been made and much
information has been obtained from GWASs. However,
GWAS-based studies to improve clinical decisions are
still in their initial stages (21). Previous studies have
focused mostly on causative loci rather than the entire
risk prediction approach. In addition, the results of
risk prediction models are not satisfactory for type 2
diabetes. Nearly 40 susceptible loci have been identified
in European and Asian populations, but the heritability
of type 2 diabetes remains largely unexplained (22). Only
~10% of the known type 2 diabetes heritability could be
explained by the results of a European twin study (23).
This evidence suggests that information on a large portion
of heritability is missing. Since a statistical P-value of 5 ×
10–8 is generally accepted for genome-wide significance
(24), previous studies did not use SNPs that had P-values
P-value
General
NHS (Female) HPFS (Male)
rs12255372
4.37E-10
9.72E-05
5.52E-07
rs12243326
6.12E-10
1.80E-04
3.47E-07
rs4132670
6.53E-10
2.56E-04
1.94E-07
rs7901695
8.18E-10
1.53E-04
5.83E-07
rs4506565
9.48E-10
1.67E-04
5.92E-07
rs11196208
2.40E-05
3.67E-03
2.08E-03
rs10885409
2.71E-05
5.33E-03
1.50E-03
rs11196205
3.49E-05
5.59E-03
1.91E-03
rs4074720
1.30E-04
1.22E-02
3.29E-03
rs7077039
1.35E-04
1.50E-02
2.77E-03
rs10787472
1.38E-04
1.36E-02
3.09E-03
rs6585201
3.96E-04
3.57E-02
2.95E-03
rs4073288
3.88E-03
>0.05
1.40E-02
rs7901275
4.71E-03
>0.05
2.25E-03
rs11196212
7.30E-03
4.39E-02
>0.05
rs7917983
7.76E-03
>0.05
2.62E-03
rs11196181
2.67E-02
>0.05
>0.05
rs12266632
3.28E-02
4.17E-02
>0.05
rs11196203
3.39E-02
>0.05
1.64E-02
greater than this. Several limitations of the current
approach for GWASs in revealing the missing heritability
information have been proposed. One limitation is that
the accepted importance threshold level for GWASs (P
< 5 × 10–8) may produce type 2 errors (false-negative
results). Therefore, many important loci could be obscured
among other loci having only borderline associations. In
addition, Imamura et al. suggested that the other reason
for the low percentage of genetic contribution might be
the omission of susceptibility variants that have an MAF
value of less than 1% (22). However, our findings do not
agree with these suggestions. In this study, we used SNPs
that had P-values of greater than 5 × 10–8, accepted 5% as
the threshold for MAF, and thereby obtained a higher risk
prediction score. The most important reason for the low
genetic contribution reported so far is that the use of a
small number of SNPs for analysis fails to yield a sufficient
composite risk score. We proposed that SNPs that have
P-values of less than the detaching point of a distribution
(in QQ plot), 1.0E-3 in our study, could contribute to risk
prediction. Furthermore, Imamura et al. (22) suggested
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GÜL et al. / Turk J Med Sci
that genome-wide exon (exome) sequencing by nextgeneration sequencers might help explain the missing
heritability. Our findings suggest that this might not be
necessary in order to obtain a high risk-prediction score.
However, next-generation sequencing technology may
help find the exact causative loci near or encompassing the
newly discovered SNPs.
Because individual SNPs do not yield adequate
prediction scores, combining SNPs to yield composite
genotype risk scores has also been tested. In such a
simulation study by Janssens et al., risk alleles were
weighted according to the type 2 diabetes effect size from
the original GWAS; this might not substantially improve
the C-statistic for alleles with small effect sizes (odds ratio:
1.10–1.25) (25). However, we found that 680 SNPs with
P-values between 1.0E-04 and 1.0E-03 yielded an overall
prediction score of 87.7% and AUC of 0.947, while 118
SNPs, with P-values of less than 1.0E-04, yielded an overall
prediction score of 67.4% and AUC of 0.735. This shows
that a high SNP number is required for higher composite
genotype risk scores. However, Janssens et al. used only 40
SNPs. The composite risk score is not equal to the sum of
individual SNP scores. Due to the overlapping effect of the
risk alleles, we could obtain a higher composite risk score
with a higher number of SNPs. However, phenotype risk
scores are higher than those of individual SNP scores, i.e.
OR is 3.86 for BMI in our study. Thus, small phenotype
variables could yield higher scores.
The prediction of an individual’s risk of developing
type 2 diabetes is the most anticipated clinical use of
genetic information. Prediction values of phenotypic and
genotypic characters have been investigated in the Malmö
Preventive Project, the Botnia Study (8), the Framingham
Offspring Study I (9), the Whitehall II study (10), and the
GoDARTS Study (26). These studies examined loci ranging
in number from 11 to 20 that were associated with type
2 diabetes. The results of these analyses showed no clear
improvement in predictive power when adding the genetic
risk score to the established risk prediction models by
using phenotypic variables such as age, sex, family history,
BMI, fasting glucose level, systolic blood pressure, and
lipid profile. Basic demographic, clinical, and laboratory
predictors have C-statistics (AUC) ranging from 0.66
in the Rotterdam Study (11) to 0.90 in the Framingham
Offspring Study I (9). The C-statistic improves from 0.903
to 0.906 with the addition of a 40-SNP score to the clinical
model in the Framingham Offspring Study II (7) and from
0.74 to 0.75 in the larger Malmö Preventive Project (8). In
other studies, adding genetic information to phenotypebased risk models did not improve discrimination and
showed a maximum increase of only 2% over phenotype
in ROC curves (6,10,26). AUC values were equal to or
lower than 0.60 for genetic variants alone in these studies
952
(9–11,26). Therefore, phenotype scores were found to be
superior to the scores achieved thus far by using genotype
alone.
Genotype-based risk prediction may work better in
younger individuals. In the Framingham Offspring II
study, the addition of a 40-SNP score to a full clinical model
achieved better net reclassification improvement (NRI)
among those younger than 50 years old (7). However, the
degree of prediction scores obtained from genotype is still
below the widely accepted clinical prevention target. The
greater contribution of genotype over the prediction value
of phenotype for patients at a younger age is expected
since phenotype variables are more overt only at middle
age or older. The most desirable risk prediction method is
one with a higher prediction value at an early age, even in
childhood. Therefore, our findings provide an opportunity
for risk prediction of type 2 diabetes with high accuracy at
an early stage.
A limitation on the use of phenotypic variables is
the reduced range of ages and follow-up durations for
type 2 diabetes genetic prediction. In previous studies,
participants with baseline ages were generally in middle
adulthood, and the follow-up period was around 10 years.
However, we need a model that can estimate the risk earlier,
which should be validated at a young age with a longer
prediction time horizon to help achieve early prevention.
As noted above, in the Framingham Offspring Study II, the
40-SNP genotype risk score significantly improved NRI in
younger participants but not in older ones. Here, we show
that genetic risk prediction alone using 798 SNPs could
yield higher risk prediction for type 2 diabetes.
Due to the low predictive value of the genetic
susceptibility loci of type 2 diabetes so far, alternative
GWAS strategies, such as enrichment of genetic effects
for improving predictive power (i.e. selecting more severe
cases, early onset of disease, and family history of type
2 diabetes), and original GWAS study designs (such as
response to an antidiabetic treatment or type 2 diabetes
in the presence of extreme obesity) (15,27) have been
proposed. Complementary epigenomic approaches such
as DNA methylation studies have also been proposed in
addition to GWAS (27). However, our strategy of using
more SNPs may provide greater risk prediction for type 2
diabetes; therefore, the need for a sophisticated approach
to risk prediction could be reviewed. Our approach
might be combined with epigenomic, environmental, or
other enrichment methods for further insight into type 2
diabetes etiology.
In the future, follow-up studies with a reasonable time
period should be designed to evaluate the development
of type 2 diabetes using the genotype-based risk
prediction value from our study. We were able to calculate
individual risk scores using the constants of the present
GÜL et al. / Turk J Med Sci
study obtained through analysis. Our findings should be
validated by comparing the cumulative type 2 diabetes
incidence in low- and high-risk groups in a follow-up
study. In addition, interethnic differences should be
reviewed from the perspective of our results, since some
GWAS studies did not mention the sex of the participants
(28,29). Furthermore, our prediction strategy could also
be tested for treatment success of type 2 diabetes by
establishing a pharmacogenetic investigation of a genomewide approach. In a previous study, it was found that a SNP,
rs11212617, at a locus containing the ataxia telangiectasia
mutated gene could explain 2.5% of the variance in the
metformin response (30). Variance greater than this can
probably be explained using the composite SNP score
approach. Translation of the findings of the present study
will provide a gateway into personalized preventive and
therapeutic medicine.
In conclusion, we found that genotype-based risk
prediction could yield higher risk prediction values when
a sufficient number of SNPs are used. This could enable
early risk prediction for type 2 diabetes. The growing
importance of the threshold P-value in GWAS analysis
should be reviewed, depending on the investigation field.
Our findings open up new horizons for translating GWAS
findings into improved care for patients with diabetes.
The value of genotype-based risk prediction alone or in
combination with phenotypic variables should be further
investigated in follow-up studies for validation.
References
1.
Magee MJ, Narayan KM. Global confluence of infectious and
non-communicable diseases – the case of type 2 diabetes. Prev
Med 2013; 57: 149–151.
2.
Poulsen P, Kyvik KO, Vaag A, Beck-Nielsen H. Heritability
of type II (non-insulin-dependent) diabetes mellitus and
abnormal glucose tolerance--a population-based twin study.
Diabetologia 1999; 42: 139–145.
3.
Riserus U, Arnlov J, Berglund L. Long-term predictors of
insulin resistance: role of lifestyle and metabolic factors in
middle-aged men. Diabetes Care 2007; 30: 2928–2933.
4.
Riserus U, Willett WC, Hu FB. Dietary fats and prevention of
type 2 diabetes. Prog Lipid Res 2009; 48: 44–51.
5.
Muhlenbruch K, Jeppesen C, Joost HG, Boeing H, Schulze MB.
The value of genetic information for diabetes risk prediction differences according to sex, age, family history and obesity.
PLoS One 2013; 8: e64307.
6.
Balkau B, Lange C, Fezeu L, Tichet J, de Lauzon-Guillain B,
Czernichow S, Fumeron F, Froguel P, Vaxillaire M, Cauchi
S et al. Predicting diabetes: clinical, biological, and genetic
approaches: data from the Epidemiological Study on the
Insulin Resistance Syndrome (DESIR). Diabetes Care 2008; 31:
2056–2061.
7.
de Miguel-Yanes JM, Shrader P, Pencina MJ, Fox CS, Manning
AK, Grant RW, Dupuis J, Florez JC, D’Agostino RB Sr, Cupples
LA et al. Genetic risk reclassification for type 2 diabetes by age
below or above 50 years using 40 type 2 diabetes risk single
nucleotide polymorphisms. Diabetes Care 2011; 34: 121–125.
10. Talmud PJ, Hingorani AD, Cooper JA, Marmot MG, Brunner
EJ, Kumari M, Kivimaki M, Humphries SE. Utility of genetic
and non-genetic risk factors in prediction of type 2 diabetes:
Whitehall II prospective cohort study. BMJ 2010; 340: b4838.
11. van Hoek M, Dehghan A, Witteman JC, van Duijn CM,
Uitterlinden AG, Oostra BA, Hofman A, Sijbrands EJ, Janssens
AC. Predicting type 2 diabetes based on polymorphisms from
genome-wide association studies: a population-based study.
Diabetes 2008; 57: 3122–3128.
12. Vaxillaire M, Veslot J, Dina C, Proenca C, Cauchi S, Charpentier
G, Tichet J, Fumeron F, Marre M, Meyre D et al. Impact of
common type 2 diabetes risk polymorphisms in the DESIR
prospective study. Diabetes 2008; 57: 244–254.
13. Vassy JL, Meigs JB. Is genetic testing useful to predict type 2
diabetes? Best Pract Res Clin Endocrinol Metabol 2012; 26: 189–
201.
14. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen
H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M,
Louheranta A, Rastas M et al. Prevention of type 2 diabetes
mellitus by changes in lifestyle among subjects with impaired
glucose tolerance. N Engl J Med 2001; 344: 1343–1350.
15. Wheeler E, Barroso I. Genome-wide association studies and type
2 diabetes. Briefings in Functional Genomics 2011; 10: 52–60.
16. Florez JC. The genetics of type 2 diabetes: a realistic appraisal in
2008. J Clin Endocrinol Metab 2008; 93: 4633–4642.
17. Billings LK, Florez JC. The genetics of type 2 diabetes: what have
we learned from GWAS? Ann N Y Acad Sci 2010; 1212: 59–77.
8.
Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi
T, Berglund G, Altshuler D, Nilsson P, Groop L. Clinical risk
factors, DNA variants, and the development of type 2 diabetes.
N Engl J Med 2008; 359: 2220–2232.
18. Blankers M, Koeter MW, Schippers GM. Missing data
approaches in eHealth research: simulation study and a tutorial
for nonmathematically inclined researchers. J Med Internet Res
2010; 12: e54.
9.
Meigs JB, Shrader P, Sullivan LM, McAteer JB, Fox CS, Dupuis
J, Manning AK, Florez JC, Wilson PW, D’Agostino RB Sr et
al. Genotype score in addition to common risk factors for
prediction of type 2 diabetes. N Engl J Med 2008; 359: 2208–
2219.
19. Tong Y, Lin Y, Zhang Y, Yang J, Zhang Y, Liu H, Zhang B.
Association between TCF7L2 gene polymorphisms and
susceptibility to type 2 diabetes mellitus: a large Human Genome
Epidemiology (HuGE) review and meta-analysis. BMC Med
Genet 2009; 10: 15.
953
GÜL et al. / Turk J Med Sci
20. Wellcome Trust Case Control C. Genome-wide association
study of 14,000 cases of seven common diseases and 3,000
shared controls. Nature 2007; 447: 661–678.
21. Lander ES. Initial impact of the sequencing of the human
genome. Nature 2011; 470: 187–197.
22. Imamura M, Maeda S. Genetics of type 2 diabetes: the GWAS
era and future perspectives [Review]. Endocr J 2011; 58: 723–
739.
23. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C,
Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G et
al. Twelve type 2 diabetes susceptibility loci identified through
large-scale association analysis. Nat Genet 2010; 42: 579–589.
24. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J,
Ioannidis JP, Hirschhorn JN. Genome-wide association studies
for complex traits: consensus, uncertainty and challenges. Nat
Rev Genet 2008; 9: 356–369.
25. Janssens AC, Moonesinghe R, Yang Q, Steyerberg EW, van
Duijn CM, Khoury MJ. The impact of genotype frequencies
on the clinical validity of genomic profiling for predicting
common chronic diseases. Genet Med 2007; 9: 528–535.
26. Lango H; UK Type 2 Diabetes Genetics Consortium, Palmer
CN, Morris AD, Zeggini E, Hattersley AT, McCarthy MI,
Frayling TM, Weedon MN. Assessing the combined impact of
18 common genetic variants of modest effect sizes on type 2
diabetes risk. Diabetes 2008; 57: 3129–3135.
954
27. Bell CG, Finer S, Lindgren CM, Wilson GA, Rakyan VK,
Teschendorff AE, Akan P, Stupka E, Down TA, Prokopenko
I et al. Integrated genetic and epigenetic analysis identifies
haplotype-specific methylation in the FTO type 2 diabetes and
obesity susceptibility locus. PLoS One 2010; 5: e14040.
28. Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott
KS, Lango H, Timpson NJ, Perry JR, Rayner NW, Freathy RM
et al. Replication of genome-wide association signals in UK
samples reveals risk loci for type 2 diabetes. Science 2007; 316:
1336–1341.
29. Yamauchi T, Hara K, Maeda S, Yasuda K, Takahashi A,
Horikoshi M, Nakamura M, Fujita H, Grarup N, Cauchi S et al.
A genome-wide association study in the Japanese population
identifies susceptibility loci for type 2 diabetes at UBE2E2 and
C2CD4A-C2CD4B. Nat Genet 2010; 42: 864–868.
30. GoDARTS and UKPDS Diabetes Pharmacogenetics Study
Group; Wellcome Trust Case Control Consortium 2, Zhou K,
Bellenguez C, Spencer CC, Bennett AJ, Coleman RL, Tavendale
R, Hawley SA, Donnelly LA et al. Common variants near ATM
are associated with glycemic response to metformin in type 2
diabetes. Nat Genet 2011; 43: 117–120.
0,8541
rs6696927
rs1562217
rs6656912
29
30
31
rs6697088
rs10889634
27
28
rs7537440
rs1373909
25
rs12142962
24
26
rs699253
rs12739235
22
23
rs11584807
rs783323
20
21
rs1587578
rs11579242
18
19
rs12131641
rs12118788
16
17
rs215792
rs215791
14
rs215773
13
15
rs6704040
rs215770
11
12
rs1546263
rs6701048
9
10
0,8585
rs7529705
rs10492998
7
8
1,154
0,8658
0,8682
0,8703
0,8708
0,8595
1,142
1,142
1,247
1,232
0,8535
0,8723
0,8304
0,8546
0,8518
0,82
0,8424
0,8776
0,8748
0,8676
1,165
1,294
1,237
1,139
0,8611
rs149562
rs6660946
1,225
5
rs11580525
4
0,7559
0,7922
0,8513
OR
6
rs11121467
rs2336381
2
rs4654582
1
3
rsid
#
2,15E-04
2,24E-04
2,89E-04
3,05E-04
8,66E-05
5,08E-04
5,02E-04
1,53E-04
3,14E-04
2,96E-05
3,10E-04
1,28E-04
9,45E-04
2,23E-04
3,08E-05
2,90E-04
8,13E-04
6,10E-04
2,84E-04
3,04E-04
7,84E-04
7,70E-04
8,28E-04
8,99E-04
8,30E-04
7,63E-04
8,72E-04
5,35E-04
9,28E-04
2,34E-04
5,28E-04
P value
0,405
0,414
0,414
0,414
0,404
0,426
0,426
0,118
0,119
0,476
0,468
0,187
0,197
0,254
0,198
0,198
0,375
0,376
0,369
0,268
0,065
0,097
0,207
0,219
0,380
0,239
0,259
0,114
0,055
0,105
0,213
MAF
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
CHR
66856259
66846154
66842969
66838499
66817312
66813463
66804495
66730690
66728087
66713736
66713368
47993041
47987966
37401328
37398350
37384100
37378878
37378028
37368827
37358560
30417261
29676041
19646020
19645434
19592679
18606142
16667788
14119518
11931611
9620920
4630143
BP
T
T
T
G
C
G
G
A
C
A
A
T
G
C
T
A
C
C
T
A
C
G
A
T
A
G
T
C
G
A
T
A1
Appendix. Chromosomes, P-values, odds ratios, and MAF values of 798 SNPs.
C
C
C
A
G
A
T
G
T
G
G
C
A
A
C
G
T
T
G
C
T
C
G
C
G
A
C
T
A
T
A
A2
84251
84251
84251
84251
84251
84251
84251
832
832
832
114819
5351
55966
EntrezGene
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
CAPZB
CAPZB
CAPZB
CROCCP3
PLOD1
AJAP1
Gene Symbol
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
capping protein (actin filament) muscle Z-line, beta
capping protein (actin filament) muscle Z-line, beta
capping protein (actin filament) muscle Z-line, beta
ciliary rootlet coiled-coil, rootletin pseudogene 3
procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1
adherens junctions associated protein 1
Gene Name
GÜL et al. / Turk J Med Sci
1
2
rs7539680
rs10753046
rs6425178
rs3919967
rs10753049
60
61
62
63
64
rs12133943
rs1208517
58
59
rs1543594
rs11579824
56
57
rs2761441
rs1942216
54
55
rs1415359
rs10493988
52
53
rs2616010
rs7550118
50
51
rs3767273
rs12046389
48
49
rs3789442
rs2220760
46
47
rs2143992
rs3789439
44
45
rs1780731
rs1434431
42
43
rs10789215
rs344935
40
41
rs7542924
rs4655506
38
39
rs6588215
rs4655650
36
37
rs6681460
rs6694782
34
35
rs4655648
rs9662943
32
33
1,248
1,252
1,248
1,25
1,232
0,8426
1,236
0,8034
0,8413
0,8648
0,8785
1,141
1,139
1,141
1,148
1,147
1,149
1,138
0,8538
0,8588
1,141
1,139
1,15
0,8661
0,8755
0,8717
0,8699
0,8726
0,8694
1,135
0,8745
0,8762
0,8718
Appendix. (Continued).
3,51E-04
1,12E-05
1,28E-05
1,18E-05
8,65E-05
2,53E-04
9,76E-04
4,74E-04
5,29E-06
2,22E-04
7,95E-04
6,23E-04
8,36E-04
9,58E-04
8,33E-04
3,74E-04
3,45E-04
2,96E-04
9,66E-04
4,95E-04
8,37E-04
5,19E-04
5,85E-04
9,22E-04
4,06E-04
5,22E-04
3,60E-04
2,78E-04
4,00E-04
2,56E-04
8,31E-04
4,57E-04
5,82E-04
0,415
0,165
0,161
0,164
0,124
0,123
0,155
0,106
0,190
0,204
0,262
0,493
0,356
0,359
0,357
0,413
0,416
0,417
0,372
0,222
0,220
0,437
0,477
0,274
0,321
0,413
0,422
0,414
0,415
0,414
0,457
0,415
0,407
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
66886897
186639485
186638225
186632905
186631148
186584179
183539106
145561705
145469224
115845877
115721322
110538385
103338744
103337029
103335690
103181905
103181688
103173621
94977931
94354044
94352014
94109636
87960918
79108612
67910451
66923773
66923399
66915643
66914874
66914537
66899350
66895645
66893720
C
A
A
C
G
G
T
G
C
A
A
G
G
C
T
C
A
G
A
C
C
C
A
C
G
T
G
G
T
A
G
A
C
T
G
C
G
C
C
C
C
T
C
C
A
A
T
C
T
C
C
G
G
T
T
G
T
A
C
A
A
C
G
A
G
T
84251
10625
607
388662
1301
1301
1301
1301
1301
1301
24
24
30836
84251
84251
84251
84251
84251
84251
84251
84251
SGIP1
IVNS1ABP
BCL9
SLC6A17
COL11A1
COL11A1
COL11A1
COL11A1
COL11A1
COL11A1
ABCA4
ABCA4
DNTTIP2
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SGIP1
SH3-domain GRB2-like (endophilin) interacting protein 1
influenza virus NS1A binding protein
B-cell CLL/lymphoma 9
solute carrier family 6, member 17
collagen, type XI, alpha 1
collagen, type XI, alpha 1
collagen, type XI, alpha 1
collagen, type XI, alpha 1
collagen, type XI, alpha 1
collagen, type XI, alpha 1
ATP-binding cassette, sub-family A (ABC1), member 4
ATP-binding cassette, sub-family A (ABC1), member 4
deoxynucleotidyltransferase, terminal, interacting protein 2
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
SH3-domain GRB2-like (endophilin) interacting protein 1
GÜL et al. / Turk J Med Sci
rs11096680
rs3796064
rs10166174
rs17803553
rs12613835
93
94
95
96
97
rs930760
rs4666438
91
92
rs11897611
rs4666430
89
90
rs3893111
rs1550105
87
88
rs2362255
rs7520116
85
86
rs2378607
rs6429366
83
84
rs17465637
rs1053316
81
82
rs2133189
rs17163358
79
80
rs2820444
rs3002142
77
78
rs2250509
rs340835
75
76
rs1119030
rs4950949
73
74
rs4428892
rs10922227
71
72
rs4313401
rs11800563
69
70
rs1565272
rs172235
67
68
rs7516670
rs6667131
65
66
0,874
0,8743
0,8685
1,16
1,15
1,156
0,8558
0,8301
0,836
0,8791
0,8655
0,8719
0,81
0,8731
0,8567
0,8119
0,8632
0,8592
0,8579
0,8268
0,8653
1,138
0,8247
0,8767
0,8829
0,882
0,8806
0,8811
1,136
1,171
1,234
1,25
1,242
Appendix. (Continued).
1,78E-05
6,66E-04
6,86E-04
3,97E-04
5,39E-04
9,87E-04
7,02E-04
8,79E-05
2,33E-04
6,05E-04
7,11E-04
4,40E-04
7,19E-04
3,66E-04
3,87E-04
1,50E-04
4,82E-04
5,02E-04
3,42E-04
2,78E-04
8,38E-04
6,80E-04
6,34E-04
7,20E-04
8,67E-04
9,94E-04
8,96E-04
7,86E-04
8,25E-04
7,69E-04
1,22E-04
4,24E-05
1,04E-05
0,164
0,356
0,356
0,349
0,260
0,270
0,264
0,355
0,173
0,161
0,444
0,302
0,329
0,126
0,426
0,315
0,117
0,281
0,284
0,283
0,129
0,276
0,473
0,129
0,372
0,485
0,486
0,495
0,496
0,499
0,296
0,165
0,164
1
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
186642303
25682705
25678607
20702484
20701799
20675712
20674067
20669817
20641940
20638798
20613584
8692795
244271398
244130482
240833628
220986518
220906461
220890152
220887262
220881065
220854685
217808443
212230298
201405593
201077185
187787822
187787128
187719770
187698667
187650996
186726999
186649670
186649073
T
A
T
A
A
A
A
C
G
C
T
G
G
G
T
T
A
A
G
C
C
A
A
A
C
A
A
T
G
A
C
A
T
C
G
C
G
G
T
G
T
A
T
C
A
C
A
C
G
G
C
A
T
T
G
G
G
T
G
G
A
C
G
A
G
A
1838
1838
64342
64342
64754
64754
400823
375056
375056
375056
375056
5629
4608
DTNB
DTNB
HS1BP3
HS1BP3
SMYD3
SMYD3
FAM177B
MIA3
MIA3
MIA3
MIA3
PROX1
MYBPH
dystrobrevin, beta
dystrobrevin, beta
HCLS1 binding protein 3
HCLS1 binding protein 3
SET and MYND domain containing 3
SET and MYND domain containing 3
family with sequence similarity 177, member B
melanoma inhibitory activity family, member 3
melanoma inhibitory activity family, member 3
melanoma inhibitory activity family, member 3
melanoma inhibitory activity family, member 3
prospero homeobox 1
myosin binding protein H
GÜL et al. / Turk J Med Sci
3
4
rs4954045
rs17786300
rs1355421
rs1355420
127
129
130
rs17575791
126
128
rs6705790
rs17010780
124
125
rs17715688
rs17715867
122
123
rs2118836
rs11123406
120
121
rs1159764
rs10221769
118
119
rs12470994
rs1159766
116
117
rs359274
rs17662176
114
115
rs4672367
rs17329726
112
113
rs1446441
rs7575107
110
111
rs17043120
rs1843032
108
109
rs6720390
rs13430296
106
107
rs2552356
rs12622811
104
105
rs17730780
rs6545274
102
103
rs3821153
rs2727880
100
101
rs7562790
rs2160367
98
99
0,7953
0,7852
1,189
0,8795
0,8652
0,8116
1,175
0,7716
0,8029
1,147
1,165
1,158
1,15
1,151
1,288
0,7373
1,175
1,23
0,8309
1,228
0,828
1,138
0,8574
0,8517
1,139
0,8602
0,8732
0,8526
0,8557
1,141
1,139
1,148
1,146
Appendix. (Continued).
3,94E-04
1,12E-04
4,95E-05
9,41E-04
9,06E-04
6,66E-04
4,87E-04
5,21E-04
2,45E-04
2,28E-04
4,66E-04
2,46E-04
5,05E-04
9,47E-04
8,91E-04
3,02E-04
1,65E-04
9,55E-04
2,03E-04
2,06E-04
1,94E-04
2,42E-04
8,27E-04
1,70E-04
8,30E-05
6,06E-04
2,44E-04
3,56E-04
3,46E-04
4,53E-04
5,83E-04
6,86E-04
3,09E-04
0,399
0,119
0,118
0,149
0,390
0,283
0,113
0,213
0,078
0,113
0,365
0,292
0,276
0,273
0,273
0,082
0,059
0,178
0,129
0,176
0,133
0,170
0,396
0,313
0,313
0,467
0,303
0,459
0,233
0,236
0,429
0,417
0,429
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
36527059
160621517
160621464
140253872
133695340
129802415
124531274
121609358
115096853
115089550
111667012
96526699
72332562
72317874
72317749
67528010
64950508
60360385
60338590
60251920
55159490
53155170
52694816
52679905
52672168
52654578
52641453
52508248
52497718
52416883
52408156
36606626
36535123
G
T
A
C
A
T
G
T
C
G
T
C
T
A
T
A
G
C
A
T
G
T
A
G
G
C
T
G
C
G
C
G
G
T
C
G
A
C
C
T
A
A
T
C
T
A
T
C
C
C
G
G
C
T
C
G
A
C
T
C
A
T
A
T
T
C
51232
22925
22925
344148
129684
57628
57628
23233
23233
23233
51232
51232
CRIM1
PLA2R1
PLA2R1
NCKAP5
CNTNAP5
DPP10
DPP10
EXOC6B
EXOC6B
EXOC6B
CRIM1
CRIM1
cysteine rich transmembrane BMP regulator 1 (chordin-like)
phospholipase A2 receptor 1, 180kDa
phospholipase A2 receptor 1, 180kDa
NCK-associated protein 5
contactin associated protein-like 5
dipeptidyl-peptidase 10 (non-functional)
dipeptidyl-peptidase 10 (non-functional)
exocyst complex component 6B
exocyst complex component 6B
exocyst complex component 6B
cysteine rich transmembrane BMP regulator 1 (chordin-like)
cysteine rich transmembrane BMP regulator 1 (chordin-like)
GÜL et al. / Turk J Med Sci
rs4664323
rs13009374
rs6742799
rs6752569
rs13390172
159
160
161
162
163
rs12998587
rs7587102
157
158
rs11693602
rs10929982
155
156
rs9287795
rs6718526
153
154
rs10165319
rs4538150
151
152
rs4386280
rs4664013
149
150
rs7593730
rs4589705
147
148
rs9917155
rs4077463
145
146
rs12692590
rs12692592
143
144
rs1020731
rs1020732
141
142
rs12692588
rs7572970
139
140
rs2925757
rs13023477
137
138
rs12692585
rs10181181
135
136
rs7573469
rs3111397
133
134
rs4665146
rs16844742
131
132
1,169
1,15
0,8377
0,8469
0,8711
0,8384
0,8344
0,8021
0,8048
0,7817
0,8055
0,8508
0,8585
0,8334
0,8605
0,806
0,8053
0,807
0,8574
0,8126
0,8606
0,8552
0,8064
0,8261
0,8511
1,176
0,7906
0,809
1,163
0,8201
0,7916
0,7949
0,8047
Appendix. (Continued).
5,34E-05
1,69E-04
4,89E-04
2,39E-04
5,84E-05
3,11E-04
1,99E-05
1,19E-05
4,55E-06
2,29E-06
2,74E-07
2,66E-06
2,18E-05
1,41E-04
6,49E-06
7,99E-05
2,75E-06
2,55E-06
3,16E-06
5,20E-05
5,95E-06
9,21E-05
4,42E-05
2,45E-07
5,97E-06
2,43E-05
8,11E-04
1,71E-06
4,03E-07
4,91E-04
2,58E-05
1,27E-05
1,94E-05
0,147
0,287
0,327
0,198
0,305
0,428
0,306
0,307
0,195
0,219
0,197
0,218
0,451
0,337
0,331
0,449
0,219
0,218
0,218
0,454
0,221
0,419
0,422
0,293
0,281
0,435
0,193
0,183
0,290
0,254
0,204
0,149
0,148
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
160624329
161233847
161182219
161025706
160973345
160967931
160967528
160950541
160944523
160932904
160922421
160918034
160917573
160901051
160892410
160891041
160884382
160879700
160874480
160871805
160871627
160861443
160852485
160852301
160844902
160832428
160820133
160809415
160795657
160789087
160759609
160653973
160639530
A
C
C
C
C
C
T
T
C
C
T
C
G
T
G
A
T
T
A
C
G
C
G
G
A
C
T
G
T
G
C
G
T
C
T
T
A
A
T
C
C
T
T
C
G
A
C
C
G
A
C
G
A
T
G
A
A
G
T
C
A
C
A
T
A
A
22925
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
5937
3694
PLA2R1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
RBMS1
ITGB6
phospholipase A2 receptor 1, 180kDa
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
RNA binding motif, single stranded interacting protein 1
integrin, beta 6
GÜL et al. / Turk J Med Sci
5
6
rs969494
rs970816
rs7595029
rs4663596
193
195
196
rs10933000
192
194
rs4673054
rs2203733
190
191
rs16840004
rs7585736
188
189
rs1075041
rs2663891
186
187
rs10198084
rs6435252
184
185
rs4675425
rs7583852
182
183
rs4241279
rs6739080
180
181
rs13010985
rs719736
178
179
rs1526212
rs10497643
176
177
rs2369202
rs12232884
174
175
rs10176147
rs826186
172
173
rs10190741
rs12477346
170
171
rs1402108
rs12185628
168
169
rs4368343
rs16851382
166
167
rs12473293
rs4383351
164
165
1,203
1,218
0,8605
0,8637
0,8657
0,8618
0,8649
1,17
1,298
1,267
1,22
1,229
0,8448
0,8505
0,8212
1,216
1,236
1,137
1,15
1,137
1,135
1,135
1,134
0,8776
1,138
0,8777
0,8765
1,207
0,8632
1,21
1,198
1,172
1,18
Appendix. (Continued).
6,70E-05
2,29E-04
7,62E-05
7,28E-05
1,07E-04
1,37E-04
8,41E-05
1,25E-04
7,85E-04
8,31E-04
9,40E-04
7,58E-04
4,89E-04
4,67E-05
4,74E-04
6,52E-04
8,61E-04
3,06E-04
7,00E-04
2,49E-04
6,98E-04
8,54E-04
8,70E-04
9,11E-04
7,66E-04
6,24E-04
6,60E-04
5,27E-04
4,01E-05
6,78E-04
1,55E-04
4,39E-06
1,35E-04
0,287
0,167
0,168
0,481
0,484
0,488
0,484
0,487
0,213
0,064
0,078
0,119
0,116
0,297
0,214
0,124
0,119
0,117
0,487
0,458
0,462
0,460
0,454
0,468
0,397
0,466
0,444
0,443
0,219
0,257
0,169
0,353
0,286
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
161237591
236065943
236056702
223805584
223803302
223801654
223801345
223796106
214300694
208325193
208281566
205372981
205366261
204855576
204766132
204734173
192322352
192317911
184895389
184812923
184761027
184719102
184709630
184694310
184403897
184378789
179445855
179396117
179389216
176957972
166621721
161242897
161242414
C
A
C
G
G
G
A
A
T
A
A
A
A
A
T
A
T
T
G
A
T
A
G
T
G
G
A
T
C
G
A
C
A
A
G
T
A
A
A
G
T
G
G
G
G
G
G
G
G
G
C
A
G
C
G
C
C
A
C
G
C
T
T
G
G
G
79582
151195
117583
117583
285025
6323
SPAG16
CCNYL1
PARD3B
PARD3B
CCDC141
SCN1A
sperm associated antigen 16
cyclin Y-like 1
par-3 partitioning defective 3 homolog B (C. elegans)
par-3 partitioning defective 3 homolog B (C. elegans)
coiled-coil domain containing 141
sodium channel, voltage-gated, type I, alpha subunit
GÜL et al. / Turk J Med Sci
rs831081
rs6766190
rs291475
rs524431
225
226
227
228
rs11707184
rs831080
223
rs17400084
222
224
rs4626067
rs10155027
220
221
rs1021734
rs17288993
218
219
rs6794229
rs13061634
216
rs11917010
215
217
rs9830825
rs12485914
213
214
rs4858348
rs4858352
211
rs2130505
210
212
rs11712016
rs12185978
208
209
rs359032
rs2088620
206
rs359033
205
207
rs359025
rs359024
203
204
rs6773179
rs6442929
200
rs1161171
rs7649544
199
201
rs7630509
198
202
rs4685598
197
0,8666
1,261
1,24
0,8493
0,8579
1,184
1,254
1,254
0,8091
0,8128
0,8224
0,8717
0,8528
0,8644
1,207
1,275
0,8526
0,8554
0,8432
0,8598
1,206
0,8501
0,8549
0,86
0,8434
0,8336
0,8322
1,148
1,148
1,243
1,172
1,175
Appendix. (Continued).
5,60E-04
6,23E-04
9,16E-04
1,91E-04
3,13E-04
2,12E-04
1,46E-04
1,60E-04
2,09E-04
3,12E-04
7,23E-04
7,75E-04
2,15E-04
7,17E-04
7,85E-04
3,53E-04
4,51E-05
7,59E-05
1,43E-05
3,98E-04
7,15E-04
4,58E-04
5,74E-04
9,99E-04
2,13E-04
8,15E-05
6,51E-05
6,47E-04
7,55E-04
8,03E-04
8,62E-04
7,98E-04
0,296
0,091
0,102
0,250
0,273
0,215
0,117
0,118
0,135
0,131
0,129
0,307
0,260
0,259
0,133
0,083
0,374
0,358
0,368
0,272
0,134
0,223
0,232
0,227
0,224
0,221
0,225
0,327
0,308
0,092
0,195
0,191
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
74383584
73883578
73871082
71515298
71515191
62316084
60261426
60259909
56968071
56940107
56938384
56029117
54189989
54181107
31437904
31431027
21743250
21730685
21727970
11061367
9174613
8435932
8432379
8431789
8421265
8420729
8417494
5073759
5072993
353069
349168
348693
A
C
A
A
C
T
T
T
T
G
T
C
T
A
C
A
G
G
G
C
G
G
C
A
G
T
C
A
T
C
G
A
G
G
T
G
G
C
C
G
C
A
C
T
G
G
T
C
A
A
A
G
C
T
T
G
A
C
T
T
C
A
A
C
27086
27086
2272
2272
50650
50650
50650
26059
55799
55799
79750
79750
79750
9901
100288428
100288428
100288428
100288428
100288428
100288428
10752
10752
10752
cell adhesion molecule with homology to L1CAM (close
homolog of L1)
cell adhesion molecule with homology to L1CAM (close
homolog of L1)
cell adhesion molecule with homology to L1CAM (close
homolog of L1)
FOXP1
FOXP1
FHIT
FHIT
ARHGEF3
ARHGEF3
ARHGEF3
ERC2
CACNA2D3
CACNA2D3
ZNF385D
ZNF385D
ZNF385D
SRGAP3
forkhead box P1
forkhead box P1
fragile histidine triad
fragile histidine triad
Rho guanine nucleotide exchange factor (GEF) 3
Rho guanine nucleotide exchange factor (GEF) 3
Rho guanine nucleotide exchange factor (GEF) 3
ELKS/RAB6-interacting/CAST family member 2
calcium channel, voltage-dependent, alpha 2/delta subunit 3
calcium channel, voltage-dependent, alpha 2/delta subunit 3
zinc finger protein 385D
zinc finger protein 385D
zinc finger protein 385D
SLIT-ROBO Rho GTPase activating protein 3
LOC100288428 uncharacterized LOC100288428
LOC100288428 uncharacterized LOC100288428
LOC100288428 uncharacterized LOC100288428
LOC100288428 uncharacterized LOC100288428
LOC100288428 uncharacterized LOC100288428
LOC100288428 uncharacterized LOC100288428
CHL1
CHL1
CHL1
GÜL et al. / Turk J Med Sci
7
8
rs10034033
rs17219704
rs13150883
rs17750311
257
258
259
260
rs7662477
rs11726723
255
rs10938681
254
256
rs7613340
rs11929598
252
rs10937330
251
253
rs1402002
rs939338
249
250
rs2131017
rs1565567
247
rs10490809
246
248
rs877439
rs1522378
244
245
rs6792168
rs12695943
242
rs7646166
241
243
rs2365012
rs11715474
239
240
rs4314124
rs6796610
237
rs1132202
236
238
rs16823934
rs17281612
234
rs9840925
233
235
rs9815149
rs9816344
231
232
rs471800
rs6551483
229
230
0,8294
0,8059
1,168
1,209
1,174
1,138
0,7794
0,8355
0,8474
1,144
1,144
1,135
0,8511
0,8595
0,842
0,8768
0,8819
1,163
1,15
1,149
1,171
0,8541
0,8683
0,8663
1,216
1,208
1,162
1,342
1,141
0,8716
0,8779
0,8741
Appendix. (Continued).
9,77E-04
3,36E-04
4,64E-04
9,18E-04
1,21E-04
8,07E-04
6,44E-04
8,69E-05
2,93E-04
7,90E-04
3,64E-04
4,01E-04
8,86E-04
4,30E-04
7,95E-04
1,64E-04
5,13E-04
8,89E-04
9,81E-04
6,29E-04
4,62E-04
6,46E-05
6,97E-05
7,97E-04
6,53E-04
5,93E-04
8,85E-04
9,09E-04
7,41E-04
5,71E-04
4,77E-04
9,58E-04
0,312
0,157
0,108
0,200
0,176
0,190
0,482
0,099
0,179
0,179
0,479
0,446
0,451
0,224
0,242
0,227
0,496
0,497
0,225
0,307
0,345
0,350
0,348
0,278
0,278
0,122
0,122
0,228
0,054
0,408
0,366
0,364
3
4
4
4
4
4
4
4
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
74392334
65866784
65828632
61735051
26071049
26065365
23847568
8066769
189235958
189233423
189221460
185186762
185125488
172706855
172700255
172699449
169283231
169282596
150988107
150319263
150307102
150284605
127299894
127280603
127270322
120633181
120606689
116818374
116582546
115162780
87569165
87568689
T
G
C
A
A
T
A
A
T
C
G
G
A
A
C
G
G
C
A
C
A
T
T
A
A
C
C
A
G
C
G
C
C
A
T
G
C
G
G
G
C
T
A
A
G
T
T
A
A
T
T
T
G
G
A
G
G
G
T
G
A
T
C
T
84448
10057
10057
27333
27333
389161
6596
54946
54946
54946
55254
57514
254887
ABLIM2
ABCC5
ABCC5
GOLIM4
GOLIM4
ANKUB1
HLTF
SLC41A3
SLC41A3
SLC41A3
TMEM39A
ARHGAP31
ZDHHC23
actin binding LIM protein family, member 2
ATP-binding cassette, sub-family C (CFTR/MRP), member 5
ATP-binding cassette, sub-family C (CFTR/MRP), member 5
golgi integral membrane protein 4
golgi integral membrane protein 4
ankyrin repeat and ubiquitin domain containing 1
helicase-like transcription factor
solute carrier family 41, member 3
solute carrier family 41, member 3
solute carrier family 41, member 3
transmembrane protein 39A
Rho GTPase activating protein 31
zinc finger, DHHC-type containing 23
GÜL et al. / Turk J Med Sci
rs7660373
rs13117869
rs4863069
rs6553232
rs11942138
289
290
291
292
293
rs10050099
rs1434621
287
288
rs7683671
rs11939106
285
286
rs12501200
rs7679856
283
284
rs12644625
rs13136521
281
282
rs12505043
rs17508289
279
280
rs17475948
rs12501586
277
278
rs13107501
rs17024826
275
276
rs10019264
rs17473405
273
274
rs10433975
rs1836899
271
272
rs17024571
rs1836900
269
270
rs11931752
rs11946552
267
268
rs10006978
rs7657124
265
266
rs7377225
rs4693846
263
264
rs6849315
rs7377204
261
262
1,175
1,188
1,202
1,193
1,374
1,151
0,8766
0,8803
0,8794
0,8773
0,8522
0,8591
1,204
0,7895
1,177
1,174
1,284
1,215
1,17
1,237
1,173
1,172
1,175
1,173
1,226
1,24
1,268
1,241
1,258
0,8494
0,8562
0,8534
1,173
Appendix. (Continued).
9,60E-04
2,58E-04
2,00E-04
1,64E-05
3,19E-05
9,21E-06
8,80E-04
8,45E-04
9,63E-04
8,79E-04
7,03E-04
2,20E-04
9,10E-05
9,67E-04
1,96E-04
2,15E-04
8,91E-05
3,09E-05
5,54E-04
9,34E-04
1,54E-04
7,48E-04
8,21E-04
6,58E-04
6,12E-04
1,09E-04
4,24E-05
1,64E-05
3,38E-05
3,07E-05
1,52E-04
3,10E-04
2,29E-04
0,191
0,238
0,206
0,263
0,269
0,077
0,274
0,358
0,402
0,401
0,401
0,266
0,392
0,130
0,104
0,244
0,307
0,109
0,126
0,194
0,126
0,202
0,195
0,195
0,204
0,147
0,151
0,135
0,155
0,136
0,262
0,262
0,261
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
83795901
189969188
189947109
189928060
189923244
162915033
162869105
160343857
160335911
160334667
160315988
155170600
144425014
111935962
106334482
102874385
102861035
97002780
96983626
96971822
96970645
96966176
96966126
96960072
96958725
96942220
96940053
96938876
96914610
96898971
88728693
88727547
88727430
A
G
G
A
G
T
G
T
T
A
G
C
T
T
A
T
T
C
C
C
A
C
A
G
G
G
A
A
C
G
A
C
C
T
C
A
C
C
C
C
G
C
G
C
A
C
C
G
C
C
G
T
T
T
G
G
A
A
A
C
T
A
A
C
T
T
79966
56884
56884
54790
SCD5
FSTL5
FSTL5
TET2
stearoyl-CoA desaturase 5
follistatin-like 5
follistatin-like 5
tet methylcytosine dioxygenase 2
GÜL et al. / Turk J Med Sci
9
10
rs7726354
rs786699
325
rs16886496
322
rs7725377
rs16886448
321
323
rs16886364
320
324
rs1979398
rs16886034
318
319
rs6866823
rs6871286
316
317
rs4336383
rs6886001
314
rs1834967
313
315
rs2199214
rs1428256
311
312
rs6880526
rs6890310
309
310
rs4518345
rs4510545
307
308
rs2974591
rs4429812
305
306
rs2974602
rs13164886
303
304
rs10037115
rs8180522
301
302
rs4866046
rs4866047
299
300
rs396
rs2530913
297
rs10491222
296
298
rs1017924
rs10491223
294
295
1,315
0,8078
0,7451
0,7772
0,7709
0,7709
0,7589
0,8801
0,8781
0,8769
0,879
1,149
1,228
1,182
0,8431
0,8586
0,8558
0,8557
0,8576
0,8601
0,8784
0,8797
0,8805
0,8719
0,8766
0,8746
0,8759
0,7781
0,8796
0,8724
0,8729
1,164
Appendix. (Continued).
9,47E-04
8,76E-04
6,65E-04
3,94E-04
1,20E-04
5,91E-04
5,91E-04
3,06E-04
7,33E-04
5,92E-04
5,37E-04
6,63E-04
5,91E-04
2,95E-04
4,18E-04
8,33E-04
2,95E-04
2,22E-04
2,17E-04
2,68E-04
3,48E-04
6,79E-04
7,06E-04
8,66E-04
5,26E-04
8,77E-04
7,19E-04
8,30E-04
1,32E-04
8,05E-04
4,18E-04
4,47E-04
0,220
0,056
0,103
0,056
0,093
0,068
0,068
0,067
0,473
0,479
0,484
0,483
0,323
0,123
0,198
0,166
0,278
0,280
0,277
0,277
0,277
0,437
0,484
0,431
0,355
0,355
0,354
0,357
0,094
0,428
0,395
0,395
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
2029187
64711237
56292353
56292240
56253286
56206570
56158101
56019613
52230084
52222513
52222328
52222194
38831091
38401890
38309217
27338180
27229330
27227465
27225107
27221661
27209030
20325791
20302871
20286581
20274979
20272670
20270828
20270802
11638455
9668339
8870497
8843528
A
A
A
T
C
G
G
C
A
T
A
C
A
A
T
C
A
T
C
A
C
C
T
C
C
G
C
A
T
C
A
C
G
C
G
C
T
C
A
T
G
C
G
T
T
G
G
T
G
C
A
G
T
T
G
T
G
A
A
G
C
G
G
G
11174
4214
4214
3672
3672
3672
3672
133584
133584
1501
ADAMTS6
MAP3K1
MAP3K1
ITGA1
ITGA1
ITGA1
ITGA1
EGFLAM
EGFLAM
CTNND2
ADAM metallopeptidase with thrombospondin type 1 motif, 6
mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin
protein ligase
mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin
protein ligase
integrin, alpha 1
integrin, alpha 1
integrin, alpha 1
integrin, alpha 1
EGF-like, fibronectin type III and laminin G domains
EGF-like, fibronectin type III and laminin G domains
catenin (cadherin-associated protein), delta 2
GÜL et al. / Turk J Med Sci
rs1150644
rs686269
rs9396712
rs1240833
rs9348440
354
355
356
357
358
rs255318
rs10456781
352
353
rs6887695
rs454036
350
351
rs7709212
rs6861600
348
349
rs31330
rs2160505
346
347
rs6878559
rs13165374
344
345
rs9327165
rs4895286
342
343
rs9326826
rs9327027
340
341
rs2416248
rs11745646
338
339
rs12655815
rs1350294
336
337
rs7723767
rs12517265
334
335
rs6892259
rs456236
332
333
rs9293433
rs3846620
330
331
rs4704438
rs1422406
328
329
rs12514992
rs12516836
326
327
1,223
1,145
1,157
1,155
1,168
0,8734
1,345
1,142
1,158
1,158
1,156
0,872
0,8478
1,144
1,142
1,145
1,135
1,286
1,156
1,144
1,166
1,174
1,19
1,17
1,166
0,8798
1,224
1,229
1,134
0,8771
0,861
1,15
1,154
Appendix. (Continued).
6,33E-04
3,45E-04
6,80E-04
5,37E-04
2,84E-04
2,13E-04
4,91E-04
5,60E-05
9,82E-04
3,08E-04
3,38E-04
3,08E-04
3,34E-04
3,07E-04
8,02E-04
4,69E-04
4,64E-04
9,62E-04
7,69E-04
5,05E-04
8,64E-04
8,16E-04
4,86E-04
1,58E-04
6,16E-04
9,17E-04
8,55E-04
5,65E-04
3,40E-04
9,84E-04
5,85E-04
1,83E-04
8,41E-04
0,282
0,131
0,349
0,276
0,356
0,278
0,396
0,068
0,326
0,321
0,315
0,335
0,431
0,225
0,344
0,445
0,408
0,418
0,067
0,295
0,323
0,224
0,222
0,224
0,224
0,216
0,413
0,121
0,120
0,468
0,433
0,339
0,278
5
6
6
6
6
6
6
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
75554502
20749315
16939387
16926604
16922625
16922283
16125021
172548635
172486267
158755223
158752193
158696755
157292346
132889400
125177257
120236091
120206274
120168056
116418496
110522145
110521442
110206705
110205180
110196417
110189680
110182685
110115057
110113641
103014552
84630874
76981162
76980795
75554524
G
T
A
T
G
A
G
A
C
C
G
C
A
C
T
G
A
C
A
A
G
G
A
A
T
C
G
C
C
C
C
G
A
T
C
G
C
A
C
A
G
G
G
C
T
C
G
G
A
G
T
T
G
A
A
C
G
C
T
T
A
G
G
A
A
G
22987
54901
153222
23105
91137
91137
22987
SV2C
CDKAL1
CREBRF
FSTL4
SLC25A46
SLC25A46
SV2C
synaptic vesicle glycoprotein 2C
CDK5 regulatory subunit associated protein 1-like 1
CREB3 regulatory factor
follistatin-like 4
solute carrier family 25, member 46
solute carrier family 25, member 46
synaptic vesicle glycoprotein 2C
GÜL et al. / Turk J Med Sci
11
12
rs1341230
rs9373855
rs488282
rs10457307
388
390
391
rs4642522
387
389
rs11966310
rs11964002
385
386
rs1343232
rs17438648
383
384
rs9343877
rs6454097
381
382
rs7739908
rs16885102
379
380
rs1996679
rs9446323
377
378
rs12204627
rs9342803
375
376
rs1266825
rs3765446
373
374
rs3010529
rs761167
371
372
rs6910476
rs6458620
369
370
rs12195232
rs1361864
367
368
rs9269202
rs12202197
365
366
rs3117108
rs9268835
363
364
rs2516478
rs2523503
361
362
rs7767391
rs16894194
359
360
0,7555
1,14
1,141
0,882
0,8758
1,136
1,138
1,138
1,138
1,277
1,277
0,8226
0,7784
0,8393
0,836
0,841
0,8179
1,137
1,136
1,136
1,157
1,155
1,184
1,14
0,866
0,8605
0,8629
1,166
0,8686
1,191
1,196
1,17
1,178
Appendix. (Continued).
5,69E-04
1,56E-04
8,44E-04
7,74E-04
9,00E-04
5,66E-04
9,02E-04
7,49E-04
7,37E-04
7,49E-04
5,05E-04
5,26E-04
2,30E-04
9,65E-04
1,81E-04
6,36E-05
6,73E-04
2,42E-05
7,63E-04
7,75E-04
7,52E-04
7,94E-04
8,94E-04
9,97E-04
8,60E-04
2,60E-04
1,32E-04
3,91E-04
2,66E-04
5,92E-04
7,91E-04
3,64E-04
2,39E-04
0,198
0,071
0,363
0,363
0,482
0,407
0,418
0,418
0,418
0,415
0,077
0,076
0,157
0,067
0,216
0,241
0,172
0,204
0,428
0,466
0,471
0,262
0,261
0,164
0,371
0,360
0,363
0,289
0,303
0,305
0,152
0,168
0,276
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
20833219
116927364
106923806
106922248
82436294
82249727
82217840
82217732
82216223
82187051
79934936
79922723
75341319
72090767
71789723
71783440
71781245
71778351
52249629
52221625
52219767
48701049
48678807
48633649
48627226
39201111
39200945
32557501
32536093
32450800
31621538
31606716
28756062
C
A
A
T
C
T
A
G
A
G
T
T
T
G
G
G
C
A
T
T
T
C
C
G
G
T
C
T
A
C
A
A
A
T
G
G
G
T
G
T
A
G
A
G
A
C
T
A
C
T
T
A
C
C
T
G
A
A
C
T
C
G
G
C
G
T
54901
100128327
4172
534
CDKAL1
BET3L
MCM3
ATP6V1G2
CDK5 regulatory subunit associated protein 1-like 1
BET3 like (S. cerevisiae)
minichromosome maintenance complex component 3
ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2
GÜL et al. / Turk J Med Sci
rs4416776
rs2618989
rs450854
rs12538286
rs10270614
420
421
422
423
424
rs10225389
rs17148752
418
419
rs17735671
rs1404198
416
417
rs7787769
rs11763192
414
415
rs964126
rs2113643
412
413
rs4722932
rs17159921
410
411
rs4722930
rs12700969
408
409
rs11769156
rs10228072
406
407
rs7456390
rs7782529
404
405
rs4722483
rs17789894
402
403
rs317801
rs6902491
400
401
rs6570562
rs6908896
398
399
rs1572045
rs9321916
396
397
rs2789010
rs1416419
394
395
rs1338980
rs1998458
392
393
0,876
0,8597
0,8777
1,147
0,8519
0,7622
0,8372
0,8066
0,7745
0,8105
0,8011
1,14
1,149
1,36
1,166
1,137
1,146
1,148
1,244
0,8132
1,186
0,8228
0,8304
1,207
0,8598
1,22
0,8389
0,8315
0,8553
1,161
1,164
1,162
1,17
Appendix. (Continued).
4,64E-04
4,83E-04
3,15E-04
8,10E-04
8,54E-04
2,66E-05
2,83E-04
4,45E-04
1,46E-04
1,03E-05
6,06E-04
1,25E-04
5,56E-04
8,69E-04
3,09E-04
1,00E-04
7,82E-04
3,77E-04
2,98E-04
8,68E-04
3,11E-04
2,31E-04
4,66E-04
5,78E-04
4,71E-04
8,16E-04
2,20E-04
4,51E-04
7,90E-04
7,19E-04
7,72E-04
6,40E-04
7,43E-04
0,232
0,459
0,285
0,392
0,299
0,439
0,078
0,171
0,130
0,126
0,110
0,126
0,482
0,284
0,051
0,352
0,425
0,427
0,428
0,091
0,132
0,217
0,131
0,143
0,142
0,240
0,151
0,181
0,139
0,216
0,239
0,239
0,239
6
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
6
6
6
6
6
6
6
6
6
118325563
101624464
101536040
101485453
95193842
82814002
75092000
62973655
54052372
53034984
53002660
52963068
52104228
47620828
31123725
29578479
29552772
29552436
29542212
28545359
27264316
14784079
6709622
3159273
166381836
159010196
156869074
143879508
143878225
137972810
118369087
118368173
118367258
A
A
A
T
C
G
C
C
A
C
T
G
G
A
T
G
A
A
C
C
A
G
T
C
G
T
C
A
A
C
T
T
G
G
G
G
C
A
A
T
A
G
T
C
C
T
G
C
A
C
G
T
T
G
C
G
G
T
C
A
G
T
T
A
G
T
1523
1523
1523
3092
9586
1607
7559
94120
222553
222553
222553
CUX1
CUX1
CUX1
HIP1
CREB5
DGKB
ZNF12
SYTL3
SLC35F1
SLC35F1
SLC35F1
cut-like homeobox 1
cut-like homeobox 1
cut-like homeobox 1
huntingtin interacting protein 1
cAMP responsive element binding protein 5
diacylglycerol kinase, beta 90kDa
zinc finger protein 12
synaptotagmin-like 3
solute carrier family 35, member F1
solute carrier family 35, member F1
solute carrier family 35, member F1
GÜL et al. / Turk J Med Sci
13
14
rs12678728
rs4562310
rs4268118
rs4256587
454
456
457
rs10504242
453
455
rs12549902
rs4317621
451
452
rs4389890
rs7825337
449
450
rs4733453
rs4733456
447
448
rs12681837
rs6997728
445
446
rs11989798
rs2976405
443
444
rs2929301
rs2705042
441
442
rs1731847
rs1968853
439
440
rs361445
rs855733
437
438
rs2701016
rs2555048
435
436
rs12707008
rs6467643
433
434
rs1357674
rs11764046
431
432
rs7801931
rs10270960
429
430
rs4730053
rs10245031
427
428
rs7341475
rs4730052
425
426
0,8034
0,8079
0,7894
0,8559
0,7733
0,8807
0,8771
0,8801
0,8804
0,8799
0,8793
0,8641
0,8643
0,8705
0,7405
1,37
1,146
1,135
0,8764
0,8632
1,208
1,141
0,8703
0,8632
1,136
1,171
1,173
0,8641
0,8633
0,8761
1,171
1,166
1,179
Appendix. (Continued).
9,79E-04
1,06E-04
2,08E-04
3,93E-05
6,74E-04
2,66E-04
9,46E-04
6,57E-04
8,20E-04
8,23E-04
7,79E-04
7,26E-04
9,68E-04
9,95E-04
4,33E-04
3,97E-04
2,66E-04
5,16E-04
8,65E-04
5,00E-04
2,38E-04
7,34E-04
8,64E-04
9,73E-04
5,23E-04
8,86E-04
9,94E-04
8,70E-04
2,77E-04
2,49E-04
8,89E-04
6,34E-04
8,69E-04
0,169
0,132
0,125
0,127
0,218
0,079
0,410
0,405
0,431
0,442
0,443
0,443
0,250
0,249
0,358
0,055
0,053
0,363
0,457
0,467
0,333
0,127
0,348
0,279
0,274
0,404
0,188
0,191
0,328
0,329
0,346
0,213
0,213
7
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
7
7
7
7
7
7
7
7
7
7
7
7
7
7
103192051
63218545
63217632
63207496
62909278
59148749
41635738
41628416
41626394
33777560
33775901
33770287
27196000
27191888
24911831
22326597
17366632
9085514
9083722
155348283
148993580
141838625
135622266
135622254
135614381
131282522
119324606
119236456
117312875
117294094
117285697
104269619
104269557
A
T
G
G
G
G
A
G
C
A
A
G
T
T
A
A
T
G
C
C
A
T
C
A
T
T
G
G
C
G
C
A
C
G
C
A
C
A
A
G
A
T
G
G
A
A
G
G
C
C
A
A
T
G
C
T
C
G
C
A
A
G
C
T
G
T
5649
90362
286
23516
28601
83992
83992
375612
375612
RELN
FAM110B
ANK1
SLC39A14
TRBV6-6
CTTNBP2
CTTNBP2
LHFPL3
LHFPL3
reelin
family with sequence similarity 110, member B
ankyrin 1, erythrocytic
solute carrier family 39 (zinc transporter), member 14
T cell receptor beta variable 6-6
cortactin binding protein 2
cortactin binding protein 2
lipoma HMGIC fusion partner-like 3
lipoma HMGIC fusion partner-like 3
GÜL et al. / Turk J Med Sci
rs506086
rs491798
rs2209882
rs2013557
rs6479067
486
487
488
489
490
rs10738743
rs511545
484
485
rs676484
rs17559639
482
483
rs13300741
rs10966484
480
481
rs7041951
rs4977251
478
479
rs16923521
rs12553948
476
477
rs10964493
rs10964495
474
475
rs10465048
rs4977395
472
473
rs10811330
rs10964477
470
471
rs10960363
rs1319332
468
469
rs2514756
rs11777070
466
467
rs13278423
rs2436860
464
465
rs16928602
rs10957216
462
463
rs16928545
rs7833958
460
461
rs7832144
rs10504344
458
459
0,8569
1,206
1,256
0,8682
0,8444
0,8698
1,146
0,8709
1,141
0,8278
0,8262
1,371
1,456
1,35
1,438
1,37
1,338
1,474
1,244
1,37
1,228
1,37
1,196
1,172
1,158
1,252
0,8768
0,8109
0,8151
0,8204
0,7521
0,8093
0,8034
Appendix. (Continued).
1,35E-04
3,92E-04
9,56E-04
5,06E-04
3,00E-04
1,07E-04
3,28E-04
4,94E-04
5,63E-04
7,52E-04
1,74E-04
1,41E-04
6,35E-05
6,41E-06
1,14E-04
1,07E-05
6,32E-05
2,87E-04
7,64E-06
6,32E-06
9,75E-05
1,65E-05
2,16E-04
5,55E-04
7,54E-04
8,04E-04
5,49E-04
5,08E-04
1,14E-04
9,57E-05
1,75E-04
4,81E-06
2,11E-04
0,126
0,257
0,132
0,090
0,401
0,257
0,404
0,371
0,334
0,367
0,169
0,178
0,063
0,057
0,067
0,058
0,064
0,061
0,053
0,196
0,060
0,200
0,055
0,162
0,200
0,247
0,092
0,488
0,143
0,156
0,152
0,105
0,128
8
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
9
8
8
8
8
8
8
8
8
8
63225135
103635386
103615815
81127236
78519989
78516428
78501010
26027974
26011612
25953989
24802191
20953339
20269793
20265354
20253186
20251635
20235283
20229840
20216358
20208695
20206063
20197095
20182495
1190703
141019541
119151124
103811225
87789535
63319367
63309109
63273320
63256978
63229338
A
A
T
A
T
C
C
C
A
C
G
C
G
G
G
C
C
C
G
A
C
C
G
C
T
A
A
A
T
T
A
G
G
G
T
A
G
A
G
T
T
C
A
A
T
A
C
A
T
T
T
A
G
T
T
A
T
G
G
G
C
A
C
G
A
T
158471
158471
158471
54914
83696
2131
54714
PRUNE2
PRUNE2
PRUNE2
FOCAD
TRAPPC9
EXT1
CNGB3
prune homolog 2 (Drosophila)
prune homolog 2 (Drosophila)
prune homolog 2 (Drosophila)
focadhesin
trafficking protein particle complex 9
exostosin 1
cyclic nucleotide gated channel beta 3
GÜL et al. / Turk J Med Sci
15
16
rs2393400
rs1930455
rs1930456
rs10740725
519
520
521
522
rs1930450
rs2939583
517
518
rs2658641
rs2658630
515
516
rs11593943
rs10430541
513
514
rs11013555
rs10763790
511
rs983990
510
512
rs7913401
rs1856113
508
509
rs6482289
rs12244668
506
507
rs6482285
rs4333914
504
505
rs7085999
rs7900252
502
503
rs12246098
rs11013514
500
rs7920535
499
501
rs3802577
rs956007
rs7468351
496
497
rs10760182
495
498
rs10739816
rs10739592
493
494
rs2786716
rs1415647
491
492
0,8784
0,8447
0,8507
0,846
0,8453
0,8418
0,8453
0,8287
0,8777
0,8722
0,8642
1,149
1,157
1,159
1,154
1,145
1,143
1,156
1,143
1,163
1,141
1,174
1,155
1,147
1,176
0,8656
1,14
1,137
1,34
0,8619
0,8643
0,8623
Appendix. (Continued).
6,66E-04
9,56E-04
2,03E-04
3,87E-04
2,32E-04
2,19E-04
1,74E-04
3,09E-04
1,29E-04
7,30E-04
4,44E-04
9,06E-04
9,25E-04
2,63E-04
2,23E-04
3,30E-04
7,84E-04
7,67E-04
3,31E-04
7,67E-04
1,62E-04
9,35E-04
1,12E-04
4,55E-04
8,72E-04
1,35E-04
5,18E-04
8,33E-04
6,75E-04
2,08E-14
6,53E-04
8,06E-04
0,257
0,371
0,224
0,223
0,225
0,224
0,221
0,208
0,186
0,395
0,377
0,244
0,284
0,342
0,341
0,341
0,337
0,347
0,328
0,348
0,340
0,347
0,291
0,312
0,309
0,276
0,298
0,369
0,481
0,485
0,251
0,256
9
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
9
9
9
9
9
103636342
59460061
59414551
59414530
59414510
59412336
59410701
59409250
59394437
56494253
33585087
30831361
23858933
23846388
23844775
23844221
23841366
23816469
23810664
23808719
23802398
23800758
23799607
23786957
23774744
23761418
13361864
138114710
123452782
123011433
103656291
103636455
C
G
A
A
T
T
T
A
G
A
T
C
A
G
T
A
G
T
A
T
G
G
A
G
G
G
C
T
A
G
C
A
T
A
G
G
G
C
G
G
A
G
C
G
G
A
C
C
A
C
G
C
A
C
G
A
A
T
T
C
G
A
T
T
8829
5264
138151
153090
NRP1
PHYH
NACC2
DAB2IP
neuropilin 1
phytanoyl-CoA 2-hydroxylase
NACC family member 2, BEN and BTB (POZ) domain
containing
DAB2 interacting protein
GÜL et al. / Turk J Med Sci
rs11196208
rs10510004
rs2483593
rs1091179
rs2420928
551
552
553
554
555
rs10885409
rs12255372
549
550
rs7077039
rs11196205
547
548
rs10787472
rs12243326
545
546
rs4132670
rs6585201
543
544
rs7901695
rs4506565
541
542
rs2804614
rs4074720
539
540
rs10787019
rs2804611
537
538
rs1421503
rs2111995
535
536
rs10883942
rs12765878
533
534
rs11191841
rs7100920
531
532
rs11553840
rs17415112
529
530
rs12571751
rs703982
527
528
rs3915932
rs810517
525
526
rs11006021
rs1759365
523
524
0,8735
0,7741
0,7592
0,8647
1,173
1,292
1,172
1,17
1,157
1,292
1,155
1,144
1,282
1,278
1,28
1,156
1,235
1,245
1,146
1,16
1,164
0,8699
0,8699
0,8741
0,8746
0,837
1,323
0,8567
0,8533
0,8533
0,8544
0,8511
0,8718
Appendix. (Continued).
4,72E-04
4,36E-04
1,03E-04
4,89E-04
1,97E-04
2,40E-05
4,37E-10
2,71E-05
3,49E-05
1,35E-04
6,12E-10
1,38E-04
3,96E-04
6,53E-10
9,48E-10
8,18E-10
1,30E-04
7,72E-04
4,64E-04
9,79E-04
9,82E-04
7,37E-04
2,30E-04
2,30E-04
3,81E-04
3,97E-04
7,52E-04
7,27E-04
6,72E-05
3,05E-05
3,08E-05
4,70E-05
3,68E-04
0,377
0,408
0,092
0,062
0,373
0,472
0,302
0,472
0,473
0,467
0,295
0,474
0,459
0,331
0,331
0,328
0,476
0,107
0,107
0,306
0,226
0,227
0,486
0,486
0,488
0,500
0,156
0,054
0,395
0,452
0,452
0,409
0,226
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
59460712
123143462
116556258
116359696
116214569
114801306
114798892
114798062
114797037
114779067
114778805
114771287
114758773
114757761
114746031
114744078
114738487
113841831
113837462
109050808
107497352
107485090
105659612
105641376
105630968
105629601
99194781
82268160
80612727
80612637
80612626
80611942
59490502
C
G
A
G
A
C
T
C
C
C
C
C
A
A
T
C
T
C
C
T
G
G
C
C
T
C
A
C
G
G
T
C
A
T
A
G
A
G
T
G
T
G
T
T
A
G
G
A
T
C
T
T
G
A
A
T
T
C
T
G
T
A
A
C
G
G
3983
3983
6934
6934
6934
6934
6934
6934
6934
6934
6934
6934
6934
6934
79991
79991
51013
81619
57178
57178
57178
57178
ABLIM1
ABLIM1
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
TCF7L2
OBFC1
OBFC1
EXOSC1
TSPAN14
ZMIZ1
ZMIZ1
ZMIZ1
ZMIZ1
actin binding LIM protein 1
actin binding LIM protein 1
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
transcription factor 7-like 2 (T-cell specific, HMG-box)
oligonucleotide/oligosaccharide-binding fold containing 1
oligonucleotide/oligosaccharide-binding fold containing 1
exosome component 1
tetraspanin 14
zinc finger, MIZ-type containing 1
zinc finger, MIZ-type containing 1
zinc finger, MIZ-type containing 1
zinc finger, MIZ-type containing 1
GÜL et al. / Turk J Med Sci
17
18
rs17833579
rs17150882
rs9666479
rs7121252
585
587
588
rs17150852
584
586
rs11232429
rs11235302
582
583
rs11237675
rs17310875
580
581
rs10793350
rs10751301
578
579
rs11228506
rs644961
576
577
rs11603383
rs17709552
574
575
rs2955949
rs7115702
572
573
rs2957523
rs2926463
570
571
rs329526
rs2926461
568
569
rs2351044
rs7117077
566
567
rs4277103
rs1881820
564
565
rs2723663
rs2303493
562
563
rs7104128
rs935951
560
561
rs7075825
rs11827296
558
559
rs1322328
rs12412485
556
557
1,206
1,202
1,267
1,258
1,263
1,21
1,347
1,207
0,8708
0,8623
0,8643
0,8824
0,8812
1,245
1,174
1,175
0,863
0,8694
0,8663
0,8703
1,137
0,8411
1,169
0,8518
0,7731
0,8762
0,8763
0,8276
1,232
1,187
0,7641
1,163
0,8817
Appendix. (Continued).
9,04E-04
2,52E-04
3,35E-04
2,10E-04
5,03E-04
3,74E-04
5,02E-04
3,79E-04
7,14E-04
2,56E-04
9,09E-05
1,17E-04
9,73E-04
8,60E-04
1,59E-04
9,99E-05
9,69E-05
3,64E-04
7,23E-04
5,25E-04
7,80E-04
7,56E-04
4,65E-04
6,83E-05
1,09E-04
7,73E-05
5,63E-04
4,90E-04
2,12E-04
9,03E-04
3,63E-04
1,83E-04
6,93E-04
0,466
0,163
0,160
0,095
0,087
0,089
0,135
0,052
0,130
0,490
0,485
0,483
0,473
0,458
0,117
0,291
0,291
0,304
0,302
0,303
0,303
0,438
0,182
0,363
0,292
0,097
0,474
0,466
0,166
0,106
0,186
0,075
0,234
10
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
11
10
10
123911094
87256116
87250138
87219070
87203798
87202808
87132574
80397567
79832113
78375191
78372286
78372163
78370468
68645758
61797095
61794159
61787955
34210651
34208964
34208431
34208169
29458729
19510993
15535033
13757134
8345806
6455791
6440086
5918145
4697321
3334236
133720979
131731590
C
C
G
C
C
A
A
T
C
C
G
T
T
A
G
A
T
A
G
G
C
T
C
A
G
C
A
C
T
T
C
T
T
G
T
A
T
T
G
T
A
G
T
C
C
C
G
A
G
A
T
T
A
T
G
T
G
C
T
G
A
G
C
T
C
G
10579
26011
26011
26011
26011
4250
4250
25841
25841
25841
25841
89797
23647
10612
TACC2
ODZ4
ODZ4
ODZ4
ODZ4
SCGB2A2
SCGB2A2
ABTB2
ABTB2
ABTB2
ABTB2
NAV2
ARFIP2
TRIM3
transforming, acidic coiled-coil containing protein 2
odz, odd Oz/ten-m homolog 4 (Drosophila)
odz, odd Oz/ten-m homolog 4 (Drosophila)
odz, odd Oz/ten-m homolog 4 (Drosophila)
odz, odd Oz/ten-m homolog 4 (Drosophila)
secretoglobin, family 2A, member 2
secretoglobin, family 2A, member 2
ankyrin repeat and BTB (POZ) domain containing 2
ankyrin repeat and BTB (POZ) domain containing 2
ankyrin repeat and BTB (POZ) domain containing 2
ankyrin repeat and BTB (POZ) domain containing 2
neuron navigator 2
ADP-ribosylation factor interacting protein 2
tripartite motif containing 3
GÜL et al. / Turk J Med Sci
rs10770836
rs10841850
rs11046122
rs10783760
rs4759173
617
618
619
620
621
rs10841848
rs11046116
615
616
rs10492118
rs6487236
613
614
rs11610942
rs10841843
611
612
rs10849045
rs7135390
609
610
rs10849040
rs17700406
607
608
rs2887474
rs10848958
605
606
rs1870199
rs10849464
603
604
rs4937342
rs433443
601
602
rs3935795
rs3935796
599
600
rs1600223
rs3935794
597
598
rs17134278
rs4559717
595
596
rs4122057
rs11020093
593
594
rs11018816
rs7937882
591
592
rs1939168
rs7101865
589
590
0,877
0,8774
1,159
1,161
1,16
1,164
1,163
1,17
1,165
1,176
0,8747
0,8718
0,862
0,864
1,147
0,8312
0,8693
0,8563
0,8733
0,8724
0,7488
0,7476
0,7216
0,7246
0,8376
1,253
1,246
0,8564
0,8374
1,225
1,225
1,174
1,17
Appendix. (Continued).
7,65E-04
8,81E-04
9,15E-04
7,69E-04
6,69E-04
6,93E-04
8,22E-04
8,61E-04
5,34E-04
9,48E-04
2,20E-04
4,42E-04
3,18E-04
1,57E-04
1,81E-04
3,01E-04
2,51E-04
2,37E-04
6,59E-05
3,73E-04
6,98E-04
2,31E-04
2,56E-04
3,45E-05
4,41E-05
4,84E-04
7,39E-04
6,85E-04
4,36E-04
6,05E-04
8,26E-05
8,87E-05
3,13E-04
0,212
0,357
0,358
0,250
0,248
0,248
0,226
0,226
0,227
0,215
0,249
0,443
0,444
0,368
0,378
0,498
0,174
0,471
0,391
0,444
0,334
0,063
0,061
0,064
0,063
0,165
0,087
0,094
0,247
0,165
0,157
0,160
0,231
11
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
11
11
11
11
11
11
11
11
11
11
11
11
11
87288340
54287453
54262230
21608288
21608123
21608008
21600886
21600821
21591183
21583225
21583158
21492898
21489968
4337744
4332859
4312167
3901365
666392
659413
656499
130876412
127903519
127896137
127896001
127895887
126798259
112656309
99106275
92267291
87619967
87579997
87579357
87577209
A
A
A
T
G
A
G
A
G
T
T
G
T
A
C
C
T
C
A
A
A
G
A
C
G
T
A
G
T
A
G
C
A
G
G
G
C
A
G
C
G
A
C
C
A
C
G
T
T
C
T
C
G
G
T
T
T
A
C
G
C
C
G
A
T
G
2998
2998
2998
2998
2998
2998
2998
2998
79912
79912
57103
57103
57103
50863
2113
2113
2113
2113
53942
120114
GYS2
GYS2
GYS2
GYS2
GYS2
GYS2
GYS2
GYS2
PYROXD1
PYROXD1
C12orf5
C12orf5
C12orf5
NTM
ETS1
ETS1
ETS1
ETS1
CNTN5
FAT3
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
glycogen synthase 2 (liver)
pyridine nucleotide-disulphide oxidoreductase domain 1
pyridine nucleotide-disulphide oxidoreductase domain 1
chromosome 12 open reading frame 5
chromosome 12 open reading frame 5
chromosome 12 open reading frame 5
neurotrimin
v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
v-ets erythroblastosis virus E26 oncogene homolog 1 (avian)
contactin 5
FAT tumor suppressor homolog 3 (Drosophila)
GÜL et al. / Turk J Med Sci
19
20
rs3825381
rs10846941
rs10773187
rs10846955
650
651
652
653
rs979589
rs3803152
648
649
rs10773182
rs2058012
646
647
rs12313339
rs11057765
644
645
rs10400410
rs11067587
642
rs4964671
641
643
rs753479
rs10860877
639
640
rs12580632
rs855287
637
638
rs12578418
rs7300815
635
636
rs12815988
rs11115663
633
rs12582634
632
634
rs1275556
rs998137
630
631
rs3851608
rs998314
628
629
rs7132617
rs10878211
626
627
rs11614506
rs3916529
624
625
rs10747758
rs4759186
622
623
1,134
1,135
1,142
0,861
0,8741
0,8686
0,879
0,8758
0,8408
0,7823
0,863
1,228
1,145
0,8429
0,8316
0,8329
1,205
1,301
0,7861
0,7634
0,7707
1,292
0,8749
0,8717
1,143
1,137
1,143
1,136
0,8284
0,8544
0,8419
0,8779
Appendix. (Continued).
9,48E-04
8,82E-04
7,97E-04
4,56E-04
6,46E-04
4,00E-04
4,55E-04
7,02E-04
6,21E-04
8,20E-04
9,90E-04
7,45E-04
9,70E-04
6,62E-04
6,74E-04
3,25E-04
6,57E-04
9,75E-04
2,15E-04
4,98E-04
9,08E-05
1,70E-04
9,45E-04
6,75E-04
6,98E-04
5,49E-04
9,35E-04
5,35E-04
9,37E-04
3,60E-04
7,92E-04
5,66E-04
0,369
0,487
0,484
0,483
0,253
0,454
0,337
0,462
0,393
0,161
0,070
0,259
0,100
0,349
0,173
0,163
0,146
0,131
0,076
0,083
0,084
0,083
0,066
0,401
0,324
0,392
0,381
0,396
0,392
0,153
0,211
0,176
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
54287594
124762711
124724088
124720392
124702816
124701148
124693655
124693362
124686312
123759382
119870876
114338107
109677882
107227824
101483695
101482692
101470239
100486792
100486144
95081078
82184765
82183441
80385922
77486027
74496341
63506634
63495765
63486189
63482244
62721863
56101942
54350346
T
T
G
T
T
G
T
G
G
C
A
C
A
G
A
G
A
C
C
A
G
T
T
C
A
G
G
C
A
G
C
A
C
C
A
C
C
A
C
A
T
T
G
T
G
C
G
A
T
T
A
G
A
C
C
G
G
A
A
T
G
A
T
G
114795
114795
114795
114795
114795
1240
8499
23329
57522
TMEM132B
TMEM132B
TMEM132B
TMEM132B
TMEM132B
CMKLR1
PPFIA2
TBC1D30
SRGAP1
transmembrane protein 132B
transmembrane protein 132B
transmembrane protein 132B
transmembrane protein 132B
transmembrane protein 132B
chemokine-like receptor 1
protein tyrosine phosphatase, receptor type, f polypeptide
(PTPRF), interacting protein (liprin), alpha 2
TBC1 domain family, member 30
SLIT-ROBO Rho GTPase activating protein 1
GÜL et al. / Turk J Med Sci
rs4942796
rs9316428
rs1407827
rs1983805
rs9591246
682
683
684
685
686
rs4258502
rs9568143
680
681
rs1888810
rs2026960
678
679
rs17357143
rs549305
676
677
rs10847919
rs452876
674
675
rs10773257
rs2010484
672
673
rs10744243
rs2346669
670
671
rs10773245
rs10773247
668
669
rs11058574
rs10847114
666
667
rs11058371
rs917337
664
665
rs11058369
rs11610391
662
663
rs6489021
rs7978045
660
661
rs6489019
rs6489020
658
659
rs7954415
rs917334
656
657
rs10846980
rs7313371
654
655
0,8627
0,8704
0,8688
0,8733
0,8653
1,148
1,14
0,8286
0,8314
1,179
0,7415
0,881
1,192
1,168
0,8732
0,8677
0,8624
0,8625
0,8667
0,8648
0,866
0,8585
1,197
0,8484
1,188
1,193
0,8455
0,8582
0,8632
0,8675
0,8642
0,8751
1,143
Appendix. (Continued).
4,13E-04
3,72E-04
7,21E-04
6,17E-04
9,53E-04
4,10E-04
2,88E-04
5,87E-04
8,28E-04
9,95E-04
8,55E-04
1,37E-04
9,55E-04
5,42E-04
1,36E-04
5,11E-04
1,78E-04
9,12E-05
9,24E-05
1,55E-04
1,24E-04
1,44E-04
8,28E-05
3,66E-05
1,61E-05
7,00E-04
5,76E-04
1,63E-05
5,91E-05
1,47E-04
2,41E-04
2,46E-04
9,86E-04
0,486
0,306
0,310
0,308
0,311
0,311
0,456
0,456
0,139
0,142
0,175
0,063
0,416
0,164
0,309
0,378
0,483
0,484
0,484
0,486
0,486
0,477
0,393
0,248
0,441
0,162
0,159
0,401
0,445
0,393
0,395
0,343
0,319
12
13
13
13
13
13
13
13
13
13
13
13
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
124857508
48704899
48609971
48608987
48526552
48484019
48468631
48461701
30458544
30442238
26037876
22504391
129326198
128706939
126298378
125292483
125264114
125260860
125260779
125257058
125256831
125256569
124903032
124894762
124894658
124891017
124873743
124872053
124866956
124866835
124864111
124862134
124861036
T
T
C
C
A
T
A
A
C
T
T
C
G
T
C
G
G
A
C
A
G
T
T
A
T
T
T
T
C
A
G
T
A
G
C
T
T
G
C
T
G
T
G
G
T
T
C
G
A
A
G
T
C
A
C
C
G
G
A
C
G
T
G
A
C
G
22862
22862
22862
22862
22862
22862
122046
10810
121256
FNDC3A
FNDC3A
FNDC3A
FNDC3A
FNDC3A
FNDC3A
TEX26
WASF3
TMEM132D
fibronectin type III domain containing 3A
fibronectin type III domain containing 3A
fibronectin type III domain containing 3A
fibronectin type III domain containing 3A
fibronectin type III domain containing 3A
fibronectin type III domain containing 3A
testis expressed 26
WAS protein family, member 3
transmembrane protein 132D
GÜL et al. / Turk J Med Sci
21
22
rs7154599
rs17764096
rs190092
rs327465
715
716
717
718
rs7144011
rs7153625
713
714
rs11159227
rs17109221
711
712
rs4243642
rs17808467
709
710
rs17119980
rs740974
707
rs1548687
706
708
rs2283381
rs10483845
704
705
rs12885258
rs2283422
702
703
rs7156200
rs12884777
700
701
rs4899384
rs10483837
698
rs1387754
697
699
rs1998193
rs28502509
695
696
rs10135562
rs6571647
693
694
rs3751488
rs424964
691
692
rs7991210
rs916048
689
690
rs1013347
rs9571208
687
688
0,8637
0,8533
0,8089
0,815
0,8089
1,165
1,164
0,8498
0,8227
0,863
0,8648
0,8615
0,8381
0,846
0,805
1,184
1,197
1,177
1,176
1,205
0,88
1,143
1,142
1,14
0,7866
1,186
1,147
1,16
1,138
1,188
1,22
0,8592
Appendix. (Continued).
2,95E-04
1,07E-04
1,40E-04
3,01E-04
4,68E-04
3,27E-04
8,36E-04
9,72E-04
8,86E-04
7,61E-04
2,33E-04
2,76E-04
2,01E-04
5,46E-05
3,15E-05
5,34E-07
1,44E-04
1,58E-04
2,35E-04
2,48E-04
1,07E-04
7,61E-04
4,85E-04
4,79E-04
5,78E-04
2,51E-04
5,23E-04
3,33E-04
9,91E-04
9,35E-04
9,62E-06
2,03E-04
0,284
0,494
0,299
0,125
0,126
0,123
0,216
0,214
0,186
0,121
0,335
0,338
0,333
0,248
0,342
0,255
0,239
0,197
0,240
0,241
0,193
0,455
0,421
0,457
0,456
0,093
0,182
0,425
0,224
0,379
0,395
0,149
13
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
14
13
13
48708882
80299793
79121236
79120259
79119562
79119015
79010136
78979872
76269385
76239145
72258454
72257827
72253994
72028222
71984874
71978830
71531955
71531051
71530913
71527435
71519244
70695709
62341315
38761768
38760507
33836835
32198399
30055554
22373934
21860760
99549906
63876687
T
C
C
T
C
A
T
T
A
A
C
G
A
A
G
G
C
A
T
C
G
T
C
C
T
G
T
A
A
A
G
C
G
T
A
G
G
G
G
C
T
G
G
A
T
G
C
A
T
G
C
A
A
A
T
T
G
A
C
G
G
C
A
T
145508
9369
9369
9369
9369
9369
9369
8110
8110
8110
9628
9628
9628
9628
9628
9628
9628
9628
27133
9472
122704
5095
CEP128
NRXN3
NRXN3
NRXN3
NRXN3
NRXN3
NRXN3
DPF3
DPF3
DPF3
RGS6
RGS6
RGS6
RGS6
RGS6
RGS6
RGS6
RGS6
KCNH5
AKAP6
MRPL52
PCCA
centrosomal protein 128kDa
neurexin 3
neurexin 3
neurexin 3
neurexin 3
neurexin 3
neurexin 3
D4, zinc and double PHD fingers, family 3
D4, zinc and double PHD fingers, family 3
D4, zinc and double PHD fingers, family 3
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
regulator of G-protein signaling 6
potassium voltage-gated channel, subfamily H (eag-related),
member 5
A kinase (PRKA) anchor protein 6
mitochondrial ribosomal protein L52
propionyl CoA carboxylase, alpha polypeptide
GÜL et al. / Turk J Med Sci
rs2131659
rs11247226
rs8033689
rs7180844
747
748
749
750
rs11629542
rs2290271
744
rs11636210
rs6495081
743
745
rs7177970
742
746
rs2059322
rs10518921
740
741
rs10083639
rs11072156
738
739
rs8030240
rs1436955
736
737
rs6494307
rs10083587
734
735
rs2456526
rs10519107
732
733
rs7180600
rs10518694
730
rs7170955
729
731
rs12592542
rs16962542
727
728
rs11848957
rs12907278
725
726
rs6574608
rs10444745
723
724
rs2888032
rs11625199
721
722
rs2556611
rs12050342
719
720
0,8721
0,8736
0,8731
0,8711
0,8803
1,154
1,152
1,139
1,242
1,242
1,246
0,8357
0,836
0,8659
0,8632
0,8756
0,8769
0,8559
1,215
1,225
1,201
1,194
0,7151
1,141
1,149
1,244
0,8628
0,8742
0,8741
0,8678
0,8686
0,8646
Appendix. (Continued).
1,19E-04
3,11E-04
4,08E-04
3,46E-04
2,84E-04
8,33E-04
1,99E-04
3,43E-04
6,53E-04
6,51E-04
6,24E-04
5,21E-04
1,82E-04
1,78E-04
8,85E-04
7,29E-04
5,60E-04
6,36E-04
3,93E-05
2,77E-04
1,58E-04
5,53E-04
1,32E-04
4,52E-05
5,00E-04
2,60E-04
7,53E-04
1,00E-04
3,77E-04
3,73E-04
1,77E-04
2,07E-04
0,495
0,473
0,434
0,468
0,475
0,434
0,472
0,358
0,435
0,104
0,105
0,106
0,191
0,193
0,263
0,259
0,413
0,413
0,481
0,145
0,142
0,151
0,209
0,057
0,456
0,451
0,096
0,470
0,500
0,498
0,500
0,492
14
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
14
14
14
14
14
14
80415919
98953582
98951820
98938486
98925810
89415484
87899758
83248639
71903355
68832308
68793963
68792114
68369472
68368811
60191674
60186856
60185825
60181982
59114168
50876734
50859965
50857433
44444884
34189070
31773110
31760469
94731600
87891057
80444575
80442498
80439264
80438617
A
T
G
C
T
C
C
C
G
G
T
C
A
A
T
T
T
G
G
C
A
A
C
A
A
A
C
G
A
A
C
T
G
C
C
T
G
T
G
A
T
A
C
A
T
G
C
C
C
C
C
T
C
G
A
T
G
G
G
T
C
G
T
C
145508
55180
55180
55180
9154
55075
55075
55075
6095
3175
3175
6263
6263
79789
145508
145508
145508
145508
CEP128
LINS
LINS
LINS
SLC28A1
UACA
UACA
UACA
RORA
ONECUT1
ONECUT1
RYR3
RYR3
CLMN
CEP128
CEP128
CEP128
CEP128
centrosomal protein 128kDa
lines homolog (Drosophila)
lines homolog (Drosophila)
lines homolog (Drosophila)
solute carrier family 28 (sodium-coupled nucleoside
transporter), member 1
uveal autoantigen with coiled-coil domains and ankyrin repeats
uveal autoantigen with coiled-coil domains and ankyrin repeats
uveal autoantigen with coiled-coil domains and ankyrin repeats
RAR-related orphan receptor A
one cut homeobox 1
one cut homeobox 1
ryanodine receptor 3
ryanodine receptor 3
calmin (calponin-like, transmembrane)
centrosomal protein 128kDa
centrosomal protein 128kDa
centrosomal protein 128kDa
centrosomal protein 128kDa
GÜL et al. / Turk J Med Sci
23
24
rs559655
rs3737361
rs9947011
rs6507323
780
782
783
rs2299836
779
781
rs688248
rs508816
777
778
rs555935
rs575420
775
776
rs767300
rs471999
773
774
rs10512617
rs1531797
771
772
rs8076794
rs6501238
769
770
rs4968816
rs11656969
767
768
rs228768
rs1968393
765
766
rs16964890
rs11652197
763
764
rs8062047
rs11648295
761
762
rs8063424
rs3924889
759
760
rs171125
rs216944
757
758
rs809684
rs249301
755
756
rs12597219
rs8062975
753
754
rs8055183
rs8043935
751
752
0,8509
0,8569
1,159
1,202
1,167
1,151
1,155
1,136
1,153
1,16
1,142
1,15
1,133
1,14
1,142
1,198
0,8764
1,146
1,143
0,8246
0,7752
0,8258
1,366
1,202
1,176
0,8718
1,283
1,209
1,203
1,191
1,183
1,181
1,183
Appendix. (Continued).
5,50E-04
2,93E-04
4,90E-04
3,64E-04
2,26E-04
1,90E-04
2,54E-04
2,85E-04
8,21E-04
2,39E-04
2,01E-04
9,45E-04
2,27E-04
9,67E-04
5,87E-04
4,76E-04
5,35E-04
6,27E-04
7,52E-04
9,15E-04
3,46E-04
4,36E-05
6,97E-04
2,18E-04
2,83E-04
5,47E-04
5,42E-04
3,43E-05
1,61E-04
3,94E-05
1,86E-04
3,83E-04
6,16E-04
0,187
0,244
0,249
0,295
0,173
0,287
0,393
0,342
0,421
0,387
0,329
0,328
0,488
0,487
0,460
0,461
0,150
0,398
0,320
0,333
0,150
0,106
0,134
0,052
0,172
0,208
0,356
0,110
0,165
0,227
0,200
0,195
0,183
16
18
18
18
18
18
18
18
18
18
18
18
17
17
17
17
17
17
17
17
17
17
16
16
16
16
16
16
16
16
16
16
16
919237
18680676
18674407
12821324
10055123
9840212
9839620
9838613
9838371
9835307
9834729
9830230
74333763
74205146
74181334
74172864
69822772
64200570
49919431
39547419
28478690
24567546
87432022
78457228
78426000
78424987
58798850
34618468
9377408
6322435
6311714
6310627
6306727
T
G
A
C
T
A
T
C
A
T
G
A
T
C
T
A
T
G
A
G
C
C
T
G
C
T
A
T
T
A
T
A
G
C
C
G
T
C
G
C
T
C
C
A
G
C
G
C
C
C
A
G
T
A
T
G
T
A
C
G
C
A
G
A
C
A
64788
5771
11031
11031
11031
11031
11031
11031
11031
57602
9267
64446
10014
40
2588
LMF1
PTPN2
RAB31
RAB31
RAB31
RAB31
RAB31
RAB31
RAB31
USP36
CYTH1
DNAI2
HDAC5
ASIC2
GALNS
lipase maturation factor 1
protein tyrosine phosphatase, non-receptor type 2
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
RAB31, member RAS oncogene family
ubiquitin specific peptidase 36
cytohesin 1
dynein, axonemal, intermediate chain 2
histone deacetylase 5
acid-sensing (proton-gated) ion channel 2
galactosamine (N-acetyl)-6-sulfate sulfatase
GÜL et al. / Turk J Med Sci
rs7251215
rs10409299
rs41332947
rs2876409
rs3746476
812
813
814
815
816
rs7252689
rs1017207
810
811
rs470443
rs4805258
808
809
rs9955666
rs1421521
806
807
rs607104
rs557416
804
805
rs639407
rs619662
802
803
rs476828
rs9947403
800
801
rs7235626
rs17782313
798
799
rs6567157
rs1942880
796
797
rs1539952
rs9966951
794
795
rs11664327
rs8091524
792
793
rs7234864
rs1942867
790
791
rs2056015
rs16973756
788
789
rs9304261
rs6507457
786
787
rs3911557
rs4800138
784
785
0,8168
1,141
0,8161
1,166
1,173
1,176
1,173
1,169
1,158
1,139
1,152
1,148
1,141
1,15
1,153
1,151
1,168
1,161
1,162
1,169
1,159
1,148
1,176
1,19
1,173
1,18
1,174
0,7505
1,134
0,8393
0,8586
0,8482
0,848
Appendix. (Continued).
2,06E-04
9,10E-04
7,11E-04
4,90E-04
9,10E-04
2,09E-04
8,08E-04
6,56E-04
8,10E-04
5,80E-04
9,78E-04
5,20E-04
5,53E-04
8,97E-04
3,05E-04
3,44E-04
4,18E-04
3,76E-04
7,07E-04
1,92E-04
1,02E-04
2,35E-04
6,16E-04
1,73E-04
5,56E-05
6,36E-05
8,71E-05
1,57E-04
6,68E-04
8,99E-04
9,33E-05
8,68E-04
2,15E-04
0,246
0,109
0,367
0,127
0,208
0,259
0,183
0,202
0,211
0,267
0,348
0,336
0,347
0,355
0,398
0,352
0,349
0,258
0,253
0,338
0,339
0,340
0,335
0,266
0,267
0,348
0,285
0,281
0,055
0,492
0,250
0,225
0,245
18
20
20
19
19
19
19
19
19
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18726561
36373583
15415075
55391757
41016164
39099587
39057327
33080647
32763882
72832968
60236486
56063765
56046039
56042573
56035531
56021159
56020730
56003567
56002077
55949677
55944189
55941205
55926275
55917492
55902940
55890603
55887250
55885837
36617062
32164600
18880434
18860594
18768295
T
G
A
C
G
G
A
T
A
A
A
A
G
G
A
G
T
C
C
T
T
G
A
G
C
C
A
T
G
G
T
T
G
C
A
G
T
A
A
G
C
G
G
G
G
A
C
G
A
C
T
T
G
C
T
G
A
T
T
G
C
A
T
C
C
A
671
140733
4868
4155
80206
5932
5932
BPI
MACROD2
NPHS1
MBP
FHOD3
RBBP8
RBBP8
bactericidal/permeability-increasing protein
MACRO domain containing 2
nephrosis 1, congenital, Finnish type (nephrin)
myelin basic protein
formin homology 2 domain containing 3
retinoblastoma binding protein 8
retinoblastoma binding protein 8
GÜL et al. / Turk J Med Sci
25
26
rs2831054
rs1888433
rs2831854
rs2831863
844
845
846
847
rs2826244
rs1029258
842
843
rs2826242
rs1985053
840
841
rs2826239
rs9980427
838
839
rs369347
rs158046
836
837
rs1667570
rs380220
834
835
rs2823759
rs915856
832
833
rs6089568
rs2037994
830
831
rs1468056
rs6061921
828
829
rs2257
rs6098138
826
827
rs1883553
rs487096
823
rs6020178
rs676035
822
824
rs6063438
821
825
rs16985285
rs6103716
819
820
rs6103249
rs6073055
817
818
1,159
1,162
1,139
1,167
0,8229
0,8668
0,8615
0,8687
0,873
0,8685
1,22
1,253
1,25
1,254
1,24
1,245
1,226
0,8517
0,8584
1,154
1,214
1,158
1,168
1,193
1,217
1,186
1,183
1,157
0,8374
0,8728
0,8325
Appendix. (Continued).
7,24E-04
2,21E-04
3,31E-04
8,63E-04
5,52E-04
5,69E-04
3,54E-04
2,27E-04
5,09E-04
6,81E-04
5,02E-04
4,29E-04
1,44E-04
2,02E-04
1,42E-04
3,59E-04
2,57E-04
8,93E-04
2,69E-05
6,35E-05
3,96E-04
7,76E-04
3,47E-04
9,91E-04
6,38E-05
5,20E-04
2,26E-04
3,04E-04
3,05E-04
7,84E-04
7,12E-04
0,147
0,347
0,283
0,386
0,239
0,136
0,340
0,328
0,326
0,346
0,326
0,132
0,115
0,109
0,112
0,111
0,111
0,105
0,425
0,432
0,333
0,119
0,306
0,200
0,240
0,128
0,205
0,204
0,327
0,153
0,338
20
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
20
20
20
20
20
20
20
20
20
20
20
20
20
41399350
28788692
28782159
27954964
27954865
26710675
20716906
20713786
20713322
20709933
20709622
18316684
16669662
16668953
16668591
16668120
16667957
15880541
59967110
59966907
54399395
52701411
51245861
48037347
48007523
47932666
47916399
47874575
42433044
41448057
41406604
C
T
T
T
A
C
G
G
T
A
T
C
G
A
G
A
C
A
A
C
C
T
G
C
T
G
G
T
C
T
G
T
C
C
C
G
A
C
A
C
G
G
T
A
G
A
G
G
C
G
T
G
C
C
T
C
C
A
C
A
C
A
140578
388815
388815
388815
388815
388815
6790
55816
128553
6615
23315
23315
23315
3172
CHODL
LINC00478
LINC00478
LINC00478
LINC00478
LINC00478
AURKA
DOK5
TSHZ2
SNAI1
SLC9A8
SLC9A8
SLC9A8
HNF4A
chondrolectin
long intergenic non-protein coding RNA 478
long intergenic non-protein coding RNA 478
long intergenic non-protein coding RNA 478
long intergenic non-protein coding RNA 478
long intergenic non-protein coding RNA 478
aurora kinase A
docking protein 5
teashirt zinc finger homeobox 2
snail homolog 1 (Drosophila)
solute carrier family 9, subfamily A (NHE8, cation proton
antiporter 8), member 8
solute carrier family 9, subfamily A (NHE8, cation proton
antiporter 8), member 8
solute carrier family 9, subfamily A (NHE8, cation proton
antiporter 8), member 8
hepatocyte nuclear factor 4, alpha
GÜL et al. / Turk J Med Sci
rs1999318
rs9975371
rs11701035
rs8132538
rs2835530
rs2845812
rs8127236
rs220161
rs9981459
rs2401163
rs2587103
rs713999
rs6008226
rs11090806
rs12009434
rs5979784
rs17277503
rs5914799
rs5914807
rs5960811
rs1930978
rs11091598
rs5914852
rs4379572
rs4557841
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
1,193
1,184
1,186
1,187
1,197
1,191
1,192
1,189
1,182
1,169
1,181
1,29
1,189
0,8414
0,8412
0,8312
0,823
0,8149
1,143
1,204
1,237
1,229
1,246
1,215
1,148
Appendix. (Continued).
2,75E-04
6,85E-04
9,99E-04
6,06E-04
3,48E-04
4,95E-04
4,32E-04
5,27E-04
8,38E-04
5,82E-04
2,51E-04
9,95E-04
3,71E-04
1,07E-05
8,87E-04
4,02E-04
2,92E-04
9,16E-04
8,21E-04
1,09E-04
1,20E-05
2,21E-05
5,68E-06
9,45E-04
9,33E-04
0,274
0,243
0,214
0,240
0,241
0,239
0,240
0,239
0,239
0,329
0,324
0,065
0,184
0,376
0,156
0,154
0,148
0,109
0,353
0,189
0,182
0,183
0,186
0,114
0,284
23
23
23
23
23
23
23
23
23
23
23
22
22
22
22
22
21
21
21
21
21
21
21
21
21
57383907
56968844
56948766
56927696
56927132
56870079
56867944
56840879
56833086
12876296
12875922
46777160
46243314
46210776
16528454
16511078
42681878
42422362
37271007
37220194
37199189
37197902
37162840
28817851
28817820
G
G
C
G
T
G
G
C
G
C
A
A
C
A
T
C
G
C
T
T
C
A
A
T
C
T
A
T
T
C
A
T
T
A
A
G
C
T
G
C
T
C
G
C
C
T
G
G
C
A
158584
550643
550643
23786
23786
64699
89766
3141
3141
3141
3141
3141
FAAH2
LOC550643
LOC550643
BCL2L13
BCL2L13
TMPRSS3
UMODL1
HLCS
HLCS
HLCS
HLCS
HLCS
fatty acid amide hydrolase 2
uncharacterized LOC550643
uncharacterized LOC550643
BCL2-like 13 (apoptosis facilitator)
BCL2-like 13 (apoptosis facilitator)
transmembrane protease, serine 3
uromodulin-like 1
holocarboxylase synthetase (biotin-(proprionyl-CoAcarboxylase (ATP-hydrolysing)) ligase)
holocarboxylase synthetase (biotin-(proprionyl-CoAcarboxylase (ATP-hydrolysing)) ligase)
holocarboxylase synthetase (biotin-(proprionyl-CoAcarboxylase (ATP-hydrolysing)) ligase)
holocarboxylase synthetase (biotin-(proprionyl-CoAcarboxylase (ATP-hydrolysing)) ligase)
holocarboxylase synthetase (biotin-(proprionyl-CoAcarboxylase (ATP-hydrolysing)) ligase)
GÜL et al. / Turk J Med Sci
27
28
rs5919623
rs12862591
rs12861185
rs5965955
883
884
885
886
rs2997052
rs5965947
881
rs2256173
880
882
rs2495622
rs2495626
878
879
rs6642958
rs4825603
876
877
rs5942729
rs5942752
874
875
rs10855622
873
0,8593
0,8554
0,8637
0,86
0,8593
1,213
1,204
1,219
1,215
1,206
1,215
1,22
1,216
0,8459
Appendix. (Continued).
4,87E-04
3,44E-04
7,72E-04
5,09E-04
5,27E-04
6,24E-04
9,46E-04
4,27E-04
5,13E-04
8,05E-04
9,84E-04
7,71E-04
9,40E-04
5,73E-04
0,406
0,403
0,406
0,411
0,408
0,178
0,174
0,174
0,176
0,177
0,154
0,155
0,155
0,267
23
23
23
23
23
23
23
23
23
23
23
23
23
23
144807588
144801952
144801782
144779048
144777233
117800548
117773617
117742946
117737020
117727895
108249271
108209528
108181279
85902249
A
G
G
C
C
G
C
T
G
C
G
G
A
G
T
C
T
G
T
A
T
C
T
G
A
A
G
C
3597
3597
117154
IL13RA1
IL13RA1
DACH2
interleukin 13 receptor, alpha 1
interleukin 13 receptor, alpha 1
dachshund homolog 2 (Drosophila)
GÜL et al. / Turk J Med Sci