Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry

被引：759

作者：

Pulit, Sara L. ^{[1
,2
,3
]}

Stoneman, Charli ^{[4
]}

Morris, Andrew P. ^{[5
,6
]}

Wood, AndrewR. ^{[4
]}

Glastonbury, Craig A. ^{[1
]}

Tyrrell, Jessica ^{[4
]}

Yengo, Loic ^{[7
]}

Ferreira, Teresa ^{[1
]}

Marouli, Eirini ^{[8
]}

Ji, Yingjie ^{[4
]}

Yang, Jian ^{[7
,9
]}

Jones, Samuel ^{[4
]}

Beaumont, Robin ^{[4
]}

Croteau-Chonka, Damien C. ^{[10
,11
]}

Winkler, Thomas W. ^{[12
]}

Hattersley, Andrew T. ^{[4
]}

Loos, Ruth J. F. ^{[13
]}

Hirschhorn, Joel N. ^{[14
,15
,16
,17
,18
]}

Visscher, Peter M. ^{[7
,9
]}

Frayling, Timothy M. ^{[4
]}

Yaghootkar, Hanieh ^{[4
]}

Lindgren, Cecilia M. ^{[1
,3
,6
]}

机构：

[1] Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England

[2] Univ Med Ctr Utrecht, Dept Genet, Ctr Mol Med, Utrecht, Netherlands

[3] Broad Inst, Program Med & Populat Genet, Boston, MA USA

[4] Univ Exeter, Sch Med, Royal Devon & Exeter NHS Trust, Exeter, Devon, England

[5] Univ Liverpool, Biostat Dept, Liverpool, Merseyside, England

[6] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[7] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[8] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

[9] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[10] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[11] Harvard Med Sch, Boston, MA 02115 USA

[12] Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany

[13] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

[14] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[15] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA

[16] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA

[17] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA

[18] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

来源：

HUMAN MOLECULAR GENETICS | 2019年 / 28卷 / 01期

基金：

英国医学研究理事会; 欧洲研究理事会; 美国国家卫生研究院; 英国惠康基金;

关键词：

MASS INDEX; HIP RATIO; OBESITY; BIAS; ADIPOSITY; RISK; LINK;

D O I：

10.1093/hmg/ddy327

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR above the thresholds used for metabolic syndrome. These data, made publicly available, will inform the biology of body fat distribution and its relationship with disease.

引用

页码：166 / 174

页数：9

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