title: Validation of Type 2 Diabetes Risk Variants Identified by Genome-Wide Association Studies in Northern Han Chinese.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. raopingbj@126.com.|Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, China. raopingbj@126.com.
authors: Ping
authors: P
authors: Rao
authors: Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China. yongzhou78214@163.com.
authors: Yong
authors: Y
authors: Zhou
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. gesky90@sina.com.|School of Medical Sciences, Edith Cowan University, Perth, WA 6027, Australia. gesky90@sina.com.
authors: Si-Qi
authors: SQ
authors: Ge
authors: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. anxin0907@163.com.
authors: An-Xin
authors: AX
authors: Wang
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. yuxinweigongzuo@163.com.|School of Medical Sciences, Edith Cowan University, Perth, WA 6027, Australia. yuxinweigongzuo@163.com.
authors: Xin-Wei
authors: XW
authors: Yu
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. mohali@163.com.
authors: Mohamed Ali
authors: MA
authors: Alzain
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. andrea_eleanor@hotmail.com.
authors: Andrea Katherine
authors: AK
authors: Veronica
authors: School of Public Health, Ningxia Medical University, Yinchuan 750021, China. qiu199008jing@163.com.
authors: Jing
authors: J
authors: Qiu
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. songms@ccmu.edu.cn.
authors: Man-Shu
authors: MS
authors: Song
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. zhangjie@ccmu.edu.cn.
authors: Jie
authors: J
authors: Zhang
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. wanghaostudy@163.com.
authors: Hao
authors: H
authors: Wang
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. fanghonghong79@sina.com.
authors: Hong-Hong
authors: HH
authors: Fang
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. shouyigaoqing@163.com.
authors: Qing
authors: Q
authors: Gao
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. wangy@ccmu.edu.cn.
authors: You-Xin
authors: YX
authors: Wang
authors: Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China. wei.wang@ecu.edu.au.|School of Medical Sciences, Edith Cowan University, Perth, WA 6027, Australia. wei.wang@ecu.edu.au.
authors: Wei
authors: W
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D044466:Asian People / Q000235:genetics*; D001835:Body Weight; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008077:Lipoproteins, LDL; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C490780:FAF1 protein, human; D008077:Lipoproteins, LDL; D014280:Triglycerides
keywords: FAF1; Han Chinese; genetic risk score; genetic susceptibility; type 2 diabetes