Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
Journal
Human molecular genetics
Journal Volume
23
Journal Issue
20
Pages
5492-5504
Date Issued
2014
Author(s)
Wen W.
Zheng W.
Okada Y.
Takeuchi F.
Tabara Y.
Hwang J.-Y.
Dorajoo R.
Li H.
Tsai F.-J.
Yang X.
He J.
Wu Y.
He M.
Zhang Y.
Liang J.
Guo X.
Sheu W.H.-H.
Delahanty R.
Guo X.
Kubo M.
Yamamoto K.
Ohkubo T.
Go M.J.
Liu J.J.
Gan W.
Chen C.-C.
Gao Y.
Li S.
Lee N.R.
Wu C.
Zhou X.
Song H.
Yao J.
Lee I.-T.
Long J.
Tsunoda T.
Akiyama K.
Takashima N.
Cho Y.S.
Ong R.T.
Lu L.
Chen C.-H.
Tan A.
Rice T.K.
Adair L.S.
Gui L.
Allison M.
Lee W.-J.
Cai Q.
Isomura M.
Umemura S.
Kim Y.J.
Seielstad M.
Hixson J.
Xiang Y.-B.
Isono M.
Kim B.-J.
Sim X.
Lu W.
Nabika T.
Lee J.
Lim W.-Y.
Gao Y.-T.
Takayanagi R.
Kang D.-H.
Wong T.Y.
Hsiung C.A.
Wu I.-C.
Shi J.
Choi B.Y.
Aung T.
Hu F.
Kim M.K.
Lim W.Y.
Wang T.-D.
Shin M.-H.
Lee J.
Ji B.-T.
Lee Y.-H.
Young T.L.
Shin D.H.
Chun B.-Y.
Cho M.-C.
Han B.-G.
Hwu C.-M.
Assimes T.L.
Absher D.
Yan X.
Kim E.
Kuo J.Z.
Kwon S.
Taylor K.D.
Chen Y.-D.I.
Rotter J.I.
Qi L.
Zhu D.
Wu T.
Mohlke K.L.
Gu D.
Mo Z.
Wu J.-Y.
Lin X.
Miki T.
Tai E.S.
Lee J.-Y.
Kato N.
Shu X.-O.
Tanaka T.
Abstract
Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.
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