Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.
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 WH-H., Delahanty R., Guo X., Kubo M., Yamamoto K., Ohkubo T., Go MJ., Liu JJ., Gan W., Chen C-C., Gao Y., Li S., Lee NR., Wu C., Zhou X., Song H., Yao J., Lee I-T., Long J., Tsunoda T., Akiyama K., Takashima N., Cho YS., Ong RT., Lu L., Chen C-H., Tan A., Rice TK., Adair LS., Gui L., Allison M., Lee W-J., Cai Q., Isomura M., Umemura S., Kim YJ., 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 TY., Hsiung CA., Wu I-C., Juang J-MJ., Shi J., Choi BY., Aung T., Hu F., Kim MK., Lim WY., Wang T-D., Shin M-H., Lee J., Ji B-T., Lee Y-H., Young TL., Shin DH., Chun B-Y., Cho M-C., Han B-G., Hwu C-M., Assimes TL., Absher D., Yan X., Kim E., Kuo JZ., Kwon S., Taylor KD., Chen Y-DI., Rotter JI., Qi L., Zhu D., Wu T., Mohlke KL., Gu D., Mo Z., Wu J-Y., Lin X., Miki T., Tai ES., Lee J-Y., Kato N., Shu X-O., Tanaka T.
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.