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

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

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机构: [1]Capital Med Univ, Beijing Key Lab Clin Epidemiol, Sch Publ Hlth, Beijing 100069, Peoples R China; [2]Capital Med Univ, Beijing Rehabil Hosp, Beijing 100144, Peoples R China; [3]Capital Med Univ, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing Anzhen Hosp, Beijing 100029, Peoples R China; [4]Edith Cowan Univ, Sch Med Sci, Perth, WA 6027, Australia; [5]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China; [6]Ningxia Med Univ, Sch Publ Hlth, Yinchuan 750021, Peoples R China [7]Authortowhomcorrespondenceshouldbeaddressed.
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关键词: type 2 diabetes genetic susceptibility FAF1 genetic risk score Han Chinese

摘要:
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.

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出版当年[2015]版:
大类 | 3 区 环境科学与生态学
小类 | 3 区 环境科学
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Q2 ENVIRONMENTAL SCIENCES
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第一作者机构: [1]Capital Med Univ, Beijing Key Lab Clin Epidemiol, Sch Publ Hlth, Beijing 100069, Peoples R China;
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