Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups

By Kevin M. Waters, D. Stram, M. Hassanein, L. Le Marchand, L. Wilkens, G. Maskarinec, K. Monroe, L. Kolonel, David Altshuler, B. Henderson and 1 more. 2010

209 citations recorded by the source corpus.

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; Phet = 3.8×10−4). 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.

Subfields: Genetics, Rheumatology

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Citations in the corpus

Rare and Common Variants: Twenty arguments (2011, background): “An empirical argument against pervasive rare variant effects is that common variants are often consistent across populations — such as between Caucasians and Asians — despite differences in allele frequencie”
Meta-analysis methods for genome-wide association studies and beyond (2013, background): “However, consistency across different ancestries may be higher for some common diseases 66 .”
Progress and Promise of Genome-Wide Association Studies for Human Complex Trait Genetics (2011, background): “Most GWAS signals have replicated across populations of different ethnicity (Waters et al. 2009, 2010; Teslovich et al. 2010), but in some cases differences between populations have been observed due to extreme allele frequency differences or lack of effect in one population vs. another (Kochi et…”
Correlation and Causation in the Study of Personality (2012, background): “Such research on diseases and anthropometric traits has already yielded promising dividends, including results that have been replicated across study designs, countries and ethnicities (International Consortium for Blood Pressure Genome-Wide Association Studies, 2011; Kooner et al., 2011; Lango Alle”
Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes (2012, unknown): “This interpretation, favoring common causal alleles, is in agreement with the observed consistency of T2D risk variant associations across major ancestry groups 31 .”
10 Years of GWAS Discovery: Biology, Function, and Translation. (2017, background): “In keeping with the age of these common risk alleles (which predates the diaspora of modern humans out of Africa), most common variant associations for T2D are replicated across major ethnic groups.(75,80) However, as increasingly diverse populations are genotyped and sequenced, more ethnic-specific”
New approaches to disease mapping in admixed populations (2011, unknown): “A pertinent question is whether causal variants have similar effect sizes in different populations, as suggested by recent studies of some trait”