Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups
Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups
复制标题
DOI：
10.1371/journal.pgen.1001078
复制
发表时间：
2010-08-01
期刊：
影响因子：
4.5
通讯作者：
Haiman, Christopher A.
中科院分区：
文献类型：
--
作者：
Waters, Kevin M.;Stram, Daniel O.;Haiman, Christopher A.
最近有人假设，在全基因组与T2D和其他疾病的关联研究中检测到的许多信号，尽管被观察到常见的变异，但实际上可能是由罕见的因果突变造成的。这一假说的一个预测是，等位基因关联应该是特定于群体的，因为因果突变是在建立了世界各地不同群体的迁徙之后出现的。我们选择了19个在欧洲人群中被发现与T2D风险重复相关的常见变异，并在一项大型多种族病例对照研究中对它们进行了研究(6,142例和7,403例对照)，研究对象是来自5个种族/民族的男性和女性(欧洲裔美国人、非裔美国人、拉丁裔美国人、日裔美国人和夏威夷土著人)。在跨种族群体的分析中，所有19个变种的等位基因关联与最初报告的方向相同，19个变种中有14个与风险显著相关。在汇总每个个体的风险等位基因数量时，每个等位基因的关联在所有群体中具有高度统计学意义(P<；10(-4))，并且在所有群体中相似(优势比1.09-1.12)，估计每个等位基因的影响大于其他群体(1.20；P-het=3.8x10(-4))。我们没有观察到风险分布上的种族差异，这可以解释与欧洲裔美国人相比，这些群体中2型糖尿病患病率的增加。在Goldstein关于T2D罕见突变的“合成关联”的假设下，不同种族/民族的等位基因关联的一致性没有得到预测。
It has been recently hypothesized that many of the signals detected in genome-wide association studies (GWAS) to T2D and other diseases, despite being observed to common variants, might in fact result from causal mutations that are rare. One prediction of this hypothesis is that the allelic associations should be population-specific, as the causal mutations arose after the migrations that established different populations around the world. We selected 19 common variants found to be reproducibly associated to T2D risk in European populations and studied them in a large multiethnic case-control study (6,142 cases and 7,403 controls) among men and women from 5 racial/ethnic groups (European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians). In analysis pooled across ethnic groups, the allelic associations were in the same direction as the original report for all 19 variants, and 14 of the 19 were significantly associated with risk. In summing the number of risk alleles for each individual, the per-allele associations were highly statistically significant (P < 10(-4)) and similar in all populations (odds ratios 1.09-1.12) except in Japanese Americans the estimated effect per allele was larger than in the other populations (1.20; P-het = 3.8x10(-4)). We did not observe ethnic differences in the distribution of risk that would explain the increased prevalence of type 2 diabetes in these groups as compared to European Americans. The consistency of allelic associations in diverse racial/ethnic groups is not predicted under the hypothesis of Goldstein regarding "synthetic associations'' of rare mutations in T2D.