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Int. J. Environ. Res. Public Health 2016, 13(9), 863; doi:10.3390/ijerph13090863

Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese

1
Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China
2
Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China
3
Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China
4
School of Medical Sciences, Edith Cowan University, Perth, WA 6027, Australia
5
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
6
School of Public Health, Ningxia Medical University, Yinchuan 750021, China
*
Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 10 June 2016 / Revised: 5 August 2016 / Accepted: 23 August 2016 / Published: 30 August 2016
View Full-Text   |   Download PDF [470 KB, uploaded 30 August 2016]   |  

Abstract

Background: More than 60 genetic susceptibility loci associated with type 2 diabetes mellitus (T2DM) have been established in populations of Asian and European ancestry. Given ethnic differences and environmental factors, validation of the effects of genetic risk variants with reported associations identified by Genome-Wide Association Studies (GWASs) is essential. The study aims at evaluating the associations of T2DM with 29 single nucleotide polymorphisms (SNPs) from 19 candidate genes derived from GWASs in a northern Han Chinese population. Method: In this case-control study, 461 T2DM-diagnosed patients and 434 controls were recruited at the Jidong oil field hospital (Hebei, China) from January 2009 to October 2013. A cumulative genetic risk score (cGRS) was calculated by summation of the number of risk alleles, and a weight GRS (wGRS) was calculated as the sum of risk alleles at each locus multiplied by their effect sizes for T2DM, using the independent variants selected. Result: The allelic frequency of the “A” allele at rs17106184 (Fas-associated factor 1, FAF1) was significantly higher in the T2DM patients than that of the healthy controls (11.7% vs. 6.4%, p < 0.001). Individuals in the highestquartile of wGRS had an over three-fold increased risk for developing T2DM compared with those in the lowest quartile (odds ratio = 3.06, 95% CI = 1.92–4.88, p < 0.001) adjusted for age, sex, BMI, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). The results were similar when analyzed with the cGRS. Conclusions: We confirmed the association between rs17106184 (FAF1) and T2DM in a northern Han Chinese population. The GRS calculated based on T2DM susceptibility variants may be a useful tool for predicting the T2DM susceptibility. View Full-Text
Keywords: type 2 diabetes; genetic susceptibility; FAF1; genetic risk score; Han Chinese type 2 diabetes; genetic susceptibility; FAF1; genetic risk score; Han Chinese
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    Description: Figure S1.Linkage disequilibrium (LD) plot of a 100-kb 1p33 region based on HapMap-CHB data

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MDPI and ACS Style

Rao, P.; Zhou, Y.; Ge, S.-Q.; Wang, A.-X.; Yu, X.-W.; Alzain, M.A.; Veronica, A.K.; Qiu, J.; Song, M.-S.; Zhang, J.; Wang, H.; Fang, H.-H.; Gao, Q.; Wang, Y.-X.; Wang, W. Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese. Int. J. Environ. Res. Public Health 2016, 13, 863.

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