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

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

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Abstract

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 decompositionmodel for 242monozygotic 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.
Original languageEnglish
Article number179
JournalFrontiers in Genetics
Volume9
Issue numberMAY
Number of pages9
ISSN1664-8021
DOIs
Publication statusPublished - 16. May 2018

Fingerprint

Genome-Wide Association Study
Dizygotic Twins
Body Mass Index
Twin Studies
Quantitative Trait Loci
Single Nucleotide Polymorphism

Keywords

  • Bivariate genome-wide association study
  • Obesity
  • Olfactory transduction
  • Signaling by G protein-coupled receptor
  • Twin study

Cite this

Wu, Yili ; Duan, Haiping ; Tian, Xiaocao ; Xu, Chunsheng ; Wang, Weijing ; Jiang, Wenjie ; Pang, Zengchang ; Zhang, Dongfeng ; Tan, Qihua. / Genetics of Obesity Traits : A Bivariate Genome-Wide Association Analysis. In: Frontiers in Genetics. 2018 ; Vol. 9, No. MAY.
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abstract = "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 decompositionmodel for 242monozygotic 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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author = "Yili Wu and Haiping Duan and Xiaocao Tian and Chunsheng Xu and Weijing Wang and Wenjie Jiang and Zengchang Pang and Dongfeng Zhang and Qihua Tan",
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Wu, Y, Duan, H, Tian, X, Xu, C, Wang, W, Jiang, W, Pang, Z, Zhang, D & Tan, Q 2018, 'Genetics of Obesity Traits: A Bivariate Genome-Wide Association Analysis', Frontiers in Genetics, vol. 9, no. MAY, 179. https://doi.org/10.3389/fgene.2018.00179

Genetics of Obesity Traits : A Bivariate Genome-Wide Association Analysis. / Wu, Yili; Duan, Haiping ; Tian, Xiaocao; Xu, Chunsheng; Wang, Weijing; Jiang, Wenjie; Pang, Zengchang; Zhang, Dongfeng; Tan, Qihua.

In: Frontiers in Genetics, Vol. 9, No. MAY, 179, 16.05.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Genetics of Obesity Traits

T2 - A Bivariate Genome-Wide Association Analysis

AU - Wu, Yili

AU - Duan, Haiping

AU - Tian, Xiaocao

AU - Xu, Chunsheng

AU - Wang, Weijing

AU - Jiang, Wenjie

AU - Pang, Zengchang

AU - Zhang, Dongfeng

AU - Tan, Qihua

PY - 2018/5/16

Y1 - 2018/5/16

N2 - 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 decompositionmodel for 242monozygotic 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.

AB - 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 decompositionmodel for 242monozygotic 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.

KW - Bivariate genome-wide association study

KW - Obesity

KW - Olfactory transduction

KW - Signaling by G protein-coupled receptor

KW - Twin study

U2 - 10.3389/fgene.2018.00179

DO - 10.3389/fgene.2018.00179

M3 - Journal article

C2 - 29868124

VL - 9

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

IS - MAY

M1 - 179

ER -