AUTHOR=Wu Yili , Duan Haiping , Tian Xiaocao , Xu Chunsheng , Wang Weijing , Jiang Wenjie , Pang Zengchang , Zhang Dongfeng , Tan Qihua 

TITLE=Genetics of Obesity Traits: A Bivariate Genome-Wide Association Analysis

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00179

DOI=10.3389/fgene.2018.00179

ISSN=1664-8021

ABSTRACT=<p>Previous genome-wide association studies on anthropometric measurements have identified more than 100 related loci, but only a small portion of heritability in obesity was explained. Here we present a bivariate twin study to look for the genetic variants associated with body mass index and waist-hip ratio, and to explore the obesity-related pathways in Northern Han Chinese. Cholesky decomposition model for 242 monozygotic and 140 dizygotic twin pairs indicated a moderate genetic correlation (<italic>r</italic> = 0.53, 95%CI: 0.42–0.64) between body mass index and waist-hip ratio. Bivariate genome-wide association analysis in 139 dizygotic twin pairs identified 26 associated SNPs with <italic>p</italic> &lt; 10<sup>−5</sup>. Further gene-based analysis found 291 nominally associated genes (<italic>P</italic> &lt; 0.05), including <italic>F12, HCRTR1, PHOSPHO1, DOCK2, DOCK6, DGKB, GLP1R, TRHR, MMP1, GPR55, CCK</italic>, and <italic>OR2AK2</italic>, as well as 6 enriched gene-sets with FDR &lt; 0.05. Expression quantitative trait loci analysis identified rs2242044 as a significant cis-eQTL in both the normal adipose-subcutaneous (<italic>P</italic> = 1.7 × 10<sup>−9</sup>) and adipose-visceral (<italic>P</italic> = 4.4 × 10<sup>−15</sup>) tissue. These findings may provide an important entry point to unravel genetic pleiotropy in obesity traits.</p>