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

Sara L. Pulit; Charli Stoneman; Andrew P. Morris; Andrew R. Wood; Craig A. Glastonbury; Jessica Tyrrell; Loïc Yengo; Teresa Ferreira; Eirini Marouli; Yingjie Ji; Jian Yang; Samuel Jones; Robin Beaumont; Damien C. Croteau-Chonka; Thomas W. Winkler; GIANT Consortium; Andrew. T. Hattersley; Ruth J. F. Loos; Joel N. Hirschhorn; Peter M. Visscher; Timothy M. Frayling; Hanieh Yaghootkar; Cecilia M. Lindgren

doi:10.1101/304030

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

Sara L. Pulit, Charli Stoneman, Andrew P. Morris, Andrew R. Wood, Craig A. Glastonbury, Jessica Tyrrell, Loïc Yengo, Teresa Ferreira, Eirini Marouli, Yingjie Ji, Jian Yang, Samuel Jones, Robin Beaumont, Damien C. Croteau-Chonka, Thomas W. Winkler, GIANT Consortium, Andrew. T. Hattersley, Ruth J. F. Loos, Joel N. Hirschhorn, Peter M. Visscher, Timothy M. Frayling, Hanieh Yaghootkar, Cecilia M. Lindgren

doi: https://doi.org/10.1101/304030

Sara L. Pulit

Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UKDepartment of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The NetherlandsProgram in Medical and Population Genetics, Broad Institute, Boston, MA, USA

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Charli Stoneman

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Andrew P. Morris

Biostatistics Department, University of Liverpool, Liverpool, UKWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

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Andrew R. Wood

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Craig A. Glastonbury

Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK

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Jessica Tyrrell

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Loïc Yengo

Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia

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Teresa Ferreira

Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK

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Eirini Marouli

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Yingjie Ji

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Jian Yang

Institute for Molecular Bioscience, University of Queensland, Brisbane, AustraliaQueensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia

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Samuel Jones

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Robin Beaumont

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Damien C. Croteau-Chonka

Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

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Thomas W. Winkler

Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany

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GIANT Consortium

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Andrew. T. Hattersley

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Ruth J. F. Loos

The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, the Icahn School of Medicine at Mount Sinai, New York, USA

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Joel N. Hirschhorn

Broad Institute of MIT and Harvard, Cambridge, MA, USADepartment of Genetics, Harvard Medical School, Boston, MA, USADivision of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, USADepartment of Pediatrics, Harvard Medical School, Boston, MA, USA

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Peter M. Visscher

Institute for Molecular Bioscience, University of Queensland, Brisbane, AustraliaQueensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia

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Timothy M. Frayling

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Hanieh Yaghootkar

University of Exeter Medical School, University of Exeter, Royal Devon and Exeter NHS Trust, Exeter, UK

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Cecilia M. Lindgren

Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UKProgram in Medical and Population Genetics, Broad Institute, Boston, MA, USAWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

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Abstract

We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio adjusted for BMI (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and 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 publically available, will inform the biology of body fat distribution and its relationship with disease.

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