Frontiers in Genetics (May 2018)

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

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

DOI
https://doi.org/10.3389/fgene.2018.00179
Journal volume & issue
Vol. 9

Abstract

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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 (r = 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 p < 10−5. Further gene-based analysis found 291 nominally associated genes (P < 0.05), including F12, HCRTR1, PHOSPHO1, DOCK2, DOCK6, DGKB, GLP1R, TRHR, MMP1, GPR55, CCK, and OR2AK2, as well as 6 enriched gene-sets with FDR < 0.05. Expression quantitative trait loci analysis identified rs2242044 as a significant cis-eQTL in both the normal adipose-subcutaneous (P = 1.7 × 10−9) and adipose-visceral (P = 4.4 × 10−15) tissue. These findings may provide an important entry point to unravel genetic pleiotropy in obesity traits.

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