Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Diabetes. 2012 Jun;61(6):1642-7. doi: 10.2337/db11-1296. Epub 2012 Apr 3.
Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (P(heterogeneity) < 0.05), eight were positively associated with risk (OR >1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations.
常见的 2 型糖尿病（T2D）遗传风险变异主要在欧洲和亚洲人群中被发现。我们在美国人口基因组学和流行病学联盟（16235 例糖尿病病例和 46122 例对照，包括欧洲裔美国人、非裔美国人、西班牙裔、东亚裔、美洲印第安人和夏威夷原住民）的六个主要种族/民族群体中测试了 20 个 T2D 风险变异与关联的方向是否具有普遍性。阳性关联（假定风险等位基因的比值比 [OR] >1）的比例范围从美洲印第安人中的 69%到欧洲裔美国人中的 100%。在我们观察到按种族/民族群体存在显著效应异质性的九个变异体中（P（异质性）<0.05），有八个在至少五个群体中与风险呈正相关（OR >1）。大多数遗传变异在人群中观察到的明显定向一致性关联表明，每个区域都存在共享的功能常见变异体。需要对所有位点进行精细映射，以揭示在人群内和人群间重要的风险标记。
