Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

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Authors: Wanqing Wen ; Norihiro Kato ; Joo-Yeon Hwang ; Xingyi Guo ; Yasuharu Tabara ; Huaixing Li ; Rajkumar Dorajoo ; Xiaobo Yang ; Fuu-Jen Tsai ; Shengxu Li ; Ying Wu ; Tangchun Wu ; Soriul Kim ; Xiuqing Guo ; Jun Liang ; Dmitry Shungin ; Linda S. Adair ; Koichi Akiyama ; Matthew Allison ; Qiuyin Cai ; Li-Ching Chang ; Chien-Hsiun Chen ; Yuan-Tsong Chen ; Yoon Shin Cho ; Bo Youl Choi ; Yutang Gao ; Min Jin Go ; Dongfeng Gu ; Bok-Ghee Han ; Meian He ; James E. Hixson ; Yanling Hu ; Tao Huang ; Masato Isono ; Keum Ji Jung ; Daehee Kang ; Young Jin Kim ; Yoshikuni Kita ; Juyoung Lee ; Nanette R. Lee ; Jeannette Lee ; Yiqin Wang ; Jian-Jun Liu ; Jirong Long ; Sanghoon Moon ; Yasuyuki Nakamura ; Masahiro Nakatochi ; Keizo Ohnaka ; Dabeeru Rao ; Jiajun Shi ; Jae Woong Sull ; Aihua Tan ; Hirotsugu Ueshima ; Chen Wu ; Yong-Bing Xiang ; Ken Yamamoto ; Jie Yao ; Xingwang Ye ; Mitsuhiro Yokota ; Xiaomin Zhang ; Yan Zheng ; Lu Qi ; Jerome I. Rotter ; Sun Ha Jee ; Dongxin Lin ; Karen L. Mohlke ; Jiang He ; Zengnan Mo ; Jer-Yuarn Wu ; E. Shyong Tai ; Xu Lin ; Tetsuro Miki ; Bong-Jo Kim ; Fumihiko Takeuchi ; Wei Zheng ; Xiao-Ou Shu

MeSH: Asia ; Asian Continental Ancestry Group/genetics* ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study* ; Humans ; Male ; Obesity/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci* ; Quantitative Trait, Heritable* ; Sex Factors ; Waist Circumference* ; Waist-Hip Ratio*

Abstract: Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.