New genetic loci link adipose and insulin biology to body fat distribution

Dmitry Shungin; Thomas W. Winkler; Damien C. Croteau-Chonka; Teresa Ferreira; Adam E. Lockes; Reedik Maegi; Rona J. Strawbridge; Tune H. Pers; Krista Fischer; Anne E. Justice; Tsegaselassie Workalemahu; Joseph M. W. Wu; Martin L. Buchkovich; Nancy L. Heard-Costa; Tamara S. Roman; Alexander W. Drong; Ci Song; Stefan Gustafsson; Felix R. Day; Tonu Esko; Tove Fall; Zoltan Kutalik; Jian'an Luan; Joshua C. Randall; Andre Scherag; Sailaja Vedantam; Andrew R. Wood; Jin Chen; Rudolf Fehrmann; Juha Karjalainen; Bratati Kahali; Ching-Ti Liu; Ellen M. Schmidt; Devin Absher; Najaf Amin; Denise Anderson; Marian Beekman; Jennifer L. Bragg-Gresham; Steven Buyske; Ayse Demirkan; Georg B. Ehret; Mary F. Feitosa; Anuj Goel; Anne U. Jackson; Toby Johnson; Marcus E. Kleber; Kati Kristiansson; Massimo Mangino; Irene Mateo Leach; Carolina Medina-Gomez; Cameron D. Palmer; Dorota Pasko; Sonali Pechlivaniss; Marjolein J. Peters; Inga Prokopenko; Alena Stancakova; Yun Ju Sung; Toshiko Tanakam; Alexander Teumer; Jana V. Van Vliet-Ostaptchouk; Loic Yengo; Weihua Zhang; Eva Albrecht; Johan Arnlov; Gillian M. Arscott; Stefania Bandinelli; Amy Barrett; Claire Bellis; Amanda J. Bennett; Christian Berne; Matthias Blueher; Stefan Buhringer; Fabrice Bonnet; Yvonne Boettcher; Marcel Bruinenberg; Delia B. Carba; Ida H. Caspersen; Robert Clarke; E. Warwick Daw; Joris Deelen; Ewa Deelman; Graciela Delgado; Alex S. F. Doney; Niina Eklund; Michael R. Erdos; Karol Estrada; Elodie Eury; Nele Friedrichs; Melissa E. Garcia; Vilmantas Giedraitis; Bruna Gigante; Alan S. Go; Alain Golay; Harald Grallert; Tanja B. Grammer; Juergen Graessler; Jagvir Grewal; Christopher J. Groves; Toomas Haller; Goran Hallmans; PAGE Consortium

doi:10.1038/nature14132

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New genetic loci link adipose and insulin biology to body fat distribution

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New genetic loci link adipose and insulin biology to body fat distribution

Dmitry Shungin, Thomas W. Winkler, Damien C. Croteau-Chonka, Teresa Ferreira, Adam E. Lockes, Reedik Maegi, Rona J. Strawbridge, Tune H. Pers, Krista Fischer, Anne E. Justice, …

Nature (London), Vol.518(7538), pp.187-U378

12/02/2015

DOI: https://doi.org/10.1038/nature14132

PMID: 25673412

Abstract

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Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

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Title: New genetic loci link adipose and insulin biology to body fat distribution
Creators: Dmitry Shungin - Umeå University
Thomas W. Winkler - University of Regensburg
Damien C. Croteau-Chonka - Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
Teresa Ferreira - Wellcome Centre for Human Genetics
Adam E. Lockes - Biostat
Reedik Maegi - University of Oxford
Rona J. Strawbridge - Karolinska Institutet
Tune H. Pers - Boston Children's Hospital
Krista Fischer - University of Tartu
Anne E. Justice - University of North Carolina at Chapel Hill
Tsegaselassie Workalemahu - Harvard University
Joseph M. W. Wu - Boston University
Martin L. Buchkovich - University of North Carolina at Chapel Hill
Nancy L. Heard-Costa - Framingham Heart Study
Tamara S. Roman - University of North Carolina at Chapel Hill
Alexander W. Drong - Wellcome Centre for Human Genetics
Ci Song - Karolinska Institutet
Stefan Gustafsson - Uppsala University
Felix R. Day - MRC Epidemiology Unit
Tonu Esko - University of Tartu
Tove Fall - Karolinska Institutet
Zoltan Kutalik - University Hospital of Lausanne
Jian'an Luan - University of Cambridge
Joshua C. Randall - Wellcome Centre for Human Genetics
Andre Scherag - Institut für Medizinische Informatik, Biometrie und Epidemiologie
Sailaja Vedantam - Boston Children's Hospital
Andrew R. Wood - University of Exeter
Jin Chen - College Station Medical Center
Rudolf Fehrmann - University of Groningen
Juha Karjalainen - University Medical Center Groningen
Bratati Kahali - University of Michigan–Ann Arbor
Ching-Ti Liu - Boston University
Ellen M. Schmidt - University of Michigan–Ann Arbor
Devin Absher - HudsonAlpha Institute for Biotechnology
Najaf Amin - Erasmus MC
Denise Anderson - The Kids Research Institute Australia
Marian Beekman - Leiden University Medical Center
Jennifer L. Bragg-Gresham - Biostat
Steven Buyske - Rutgers, The State University of New Jersey
Ayse Demirkan - Erasmus MC
Georg B. Ehret - Johns Hopkins Medicine
Mary F. Feitosa - Washington University in St. Louis
Anuj Goel - Wellcome Centre for Human Genetics
Anne U. Jackson - University of Michigan–Ann Arbor
Toby Johnson - SIB Swiss Institute of Bioinformatics
Marcus E. Kleber - University Medical Centre Mannheim
Kati Kristiansson - Finnish Institute for Health and Welfare
Massimo Mangino - King's College London
Irene Mateo Leach - University Medical Center Groningen
Carolina Medina-Gomez - Netherlands Consortium for Healthy Ageing
Cameron D. Palmer - Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA
Dorota Pasko - University of Exeter
Sonali Pechlivaniss - Univ Hosp Essen, IMIBE, D-45147 Essen, Germany
Marjolein J. Peters - Netherlands Consortium for Healthy Ageing
Inga Prokopenko - Wellcome Centre for Human Genetics
Alena Stancakova - University of Eastern Finland
Yun Ju Sung - Biostat
Toshiko Tanakam - NIA, Translat Gerontol Branch, Baltimore, MD 21225 USA
Alexander Teumer - Universitätsmedizin Greifswald
Jana V. Van Vliet-Ostaptchouk - University of Groningen
Loic Yengo - Université de Lille
Weihua Zhang - Ealing Hospital
Eva Albrecht - Helmholtz Zentrum München
Johan Arnlov - Science for Life Laboratory
Gillian M. Arscott - Pathwest Laboratory Medicine
Stefania Bandinelli - Azienda Sanitaria di Firenze
Amy Barrett - Oxford Centre for Diabetes, Endocrinology and Metabolism
Claire Bellis - Texas Biomedical Research Institute
Amanda J. Bennett - University of Oxford
Christian Berne - Uppsala University
Matthias Blueher - Institute of Inland Fisheries in Potsdam-Sacrow
Stefan Buhringer - Leiden University
Fabrice Bonnet - Université de Rennes
Yvonne Boettcher - Institute of Inland Fisheries in Potsdam-Sacrow
Marcel Bruinenberg - University of Groningen
Delia B. Carba - University of San Carlos
Ida H. Caspersen - Norwegian University of Science and Technology
Robert Clarke - University of Oxford
E. Warwick Daw - Washington University in St. Louis
Joris Deelen - Leiden University Medical Center
Ewa Deelman - University of Southern California
Graciela Delgado - Heidelberg University
Alex S. F. Doney - Ninewells Hospital
Niina Eklund - Finnish Institute for Health and Welfare
Michael R. Erdos - National Human Genome Research Institute
Karol Estrada - Broad Institute
Elodie Eury - Université de Lille
Nele Friedrichs - College Station Medical Center
Melissa E. Garcia - National Institute on Aging
Vilmantas Giedraitis - Uppsala University
Bruna Gigante - Karolinska Institutet
Alan S. Go - Kaiser Permanente
Alain Golay - University Hospital of Geneva
Harald Grallert - Helmholtz Zentrum München
Tanja B. Grammer - Heidelberg University
Juergen Graessler - College Station Medical Center
Jagvir Grewal - Ealing Hospital
Christopher J. Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Toomas Haller - University of Tartu
Goran Hallmans - Umeå University
PAGE Consortium
Publication Details: Nature (London), Vol.518(7538), pp.187-U378
Publisher: NATURE PORTFOLIO
Number of pages: 22
Date published: 12/02/2015
Grant note: RG/07/008/23674; FS/14/55/30806; RG/13/2/30098; RG/08/008/25291; RG/10/12/28456; RG/08/014/24067 / British Heart Foundation 14136 / Cancer Research UK CZB/4/710 / Chief Scientist Office; Chief Scientist Office - Scotland R190-2014-3904 / Lundbeck Foundation; Lundbeckfonden ES/F02679X/1; ES/J023299/1 / ESRC; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) MC_UU_12015/5; G0601463; G0600717; G0601261; MC_UU_12015/1; MC_UU_12012/1; G1000616; G0400491; MR/N01104X/1; G0902037; MC_UU_12019/1; MC_UU_12015/2; MC_PC_U127561128; MC_UU_12013/1; MR/K013351/1; MC_UP_A100_1003; MR/L003120/1; G1001799; MC_U147585827; G9521010; MC_U106179472; MC_U147585819 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NF-SI-0514-10027; NF-SI-0513-10109; NF-SI-0512-10113; NF-SI-0512-10135; NF-SI-0513-10085; NF-SI-0508-10082; NF-SI-0611-10099; NF-SI-0507-10380; NF-SI-0611-10170; NF-SI-0512-10165; NF-SI-0512-10114; NF-SI-0611-10219 / National Institute for Health Research; National Institutes of Health Research (NIHR) Pers Group / NNF Center for Basic Metabolic Research; Novo Nordisk Foundation ES/F02679X/1; ES/J023299/1 / Economic and Social Research Council; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) MC_U106179472; G0601463; MC_UU_12015/5; G0100222; G8802774; MR/K013351/1; G9521010; MC_CF023241; G0400491; G1001799; MC_U106179471; MR/N01104X/1; MC_U147585824; MC_UP_A100_1003; MC_UU_12013/1; MR/L003120/1; G0401527; G0600717B; MC_U147585819; MC_UU_12012/5/B; G0600717; G19/35; MC_UU_12015/1; G0601261; G1000616; MC_UU_12015/2; MC_UU_12012/1; U1475000001; G0902037; MR/K011480/1; MR/K006584/1; MC_UU_12011/1; G1000143; MC_PC_U127561128; MC_UU_12019/1; MC_U147585827; MC_UP_A620_1014 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC)
Identifiers: 99928705102346
Academic Unit: School of Biosciences; Institute for Sustainability; Surrey Institute for People-Centred AI
Language: English
Resource Type: Journal article

New genetic loci link adipose and insulin biology to body fat distribution

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