Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

PubMed ID: 24861553

Author(s): Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang JY, Dorajoo R, Li H, Tsai FJ, Yang X, He J, Wu Y, He M, Zhang Y, Liang J, Guo X, Sheu WH, Delahanty R, Guo X, Kubo M, Yamamoto K, Ohkubo T, Go MJ, Liu JJ, Gan W, Chen CC, Gao Y, Li S, Lee NR, Wu C, Zhou X, Song H, Yao J, Lee IT, Long J, Tsunoda T, Akiyama K, Takashima N, Cho YS, Ong RT, Lu L, Chen CH, Tan A, Rice TK, Adair LS, Gui L, Allison M, Lee WJ, Cai Q, Isomura M, Umemura S, Kim YJ, Seielstad M, Hixson J, Xiang YB, Isono M, Kim BJ, Sim X, Lu W, Nabika T, Lee J, Lim WY, Gao YT, Takayanagi R, Kang DH, Wong TY, Hsiung CA, Wu IC, Juang JM, Shi J, Choi BY, Aung T, Hu F, Kim MK, Lim WY, Wang TD, Shin MH, Lee J, Ji BT, Lee YH, Young TL, Shin DH, Chun BY, Cho MC, Han BG, Hwu CM, Assimes TL, Absher D, Yan X, Kim E, Kuo JZ, Kwon S, Taylor KD, Chen YD, Rotter JI, Qi L, Zhu D, Wu T, Mohlke KL, Gu D, Mo Z, Wu JY, Lin X, Miki T, Tai ES, Lee JY, Kato N, Shu XO, Tanaka T. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum Mol Genet. 2014 Oct 15;23(20):5492-504. doi: 10.1093/hmg/ddu248. Epub 2014 May 26. PMID 24861553

Journal: Human Molecular Genetics, Volume 23, Issue 20, Oct 2014

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.