Abstract
To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (Po5108), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Original language | English |
---|---|
Article number | 10495 |
Journal | Nature communications |
Volume | 7 |
DOIs | |
State | Published - Feb 1 2016 |
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In: Nature communications, Vol. 7, 10495, 01.02.2016.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
AU - Lu, Yingchang
AU - Day, Felix R.
AU - Gustafsson, Stefan
AU - Buchkovich, Martin L.
AU - Na, Jianbo
AU - Bataille, Veronique
AU - Cousminer, Diana L.
AU - Dastani, Zari
AU - Drong, Alexander W.
AU - Esko, Toñu
AU - Evans, David M.
AU - Falchi, Mario
AU - Feitosa, Mary F.
AU - Ferreira, Teresa
AU - Hedman, Åsa K.
AU - Haring, Robin
AU - Hysi, Pirro G.
AU - Iles, Mark M.
AU - Justice, Anne E.
AU - Kanoni, Stavroula
AU - Lagou, Vasiliki
AU - Li, Rui
AU - Li, Xin
AU - Locke, Adam
AU - Lu, Chen
AU - Mägi, Reedik
AU - Perry, John R.B.
AU - Pers, Tune H.
AU - Qi, Qibin
AU - Sanna, Marianna
AU - Schmidt, Ellen M.
AU - Scott, William R.
AU - Shungin, Dmitry
AU - Teumer, Alexander
AU - Vinkhuyzen, Anna A.E.
AU - Walker, Ryan W.
AU - Westra, Harm Jan
AU - Zhang, Mingfeng
AU - Zhang, Weihua
AU - Zhao, Jing Hua
AU - Zhu, Zhihong
AU - Afzal, Uzma
AU - Ahluwalia, Tarunveer Singh
AU - Bakker, Stephan J.L.
AU - Bellis, Claire
AU - Bonnefond, Amélie
AU - Borodulin, Katja
AU - Buchman, Aron S.
AU - Cederholm, Tommy
AU - Choh, Audrey C.
AU - Choi, Hyung Jin
AU - Curran, Joanne E.
AU - De Groot, Lisette C.P.G.M.
AU - De Jager, Philip L.
AU - Dhonukshe-Rutten, Rosalie A.M.
AU - Enneman, Anke W.
AU - Eury, Elodie
AU - Evans, Daniel S.
AU - Forsen, Tom
AU - Friedrich, Nele
AU - Fumeron, Frédéric
AU - Garcia, Melissa E.
AU - Gärtner, Simone
AU - Han, Bok Ghee
AU - Havulinna, Aki S.
AU - Hayward, Caroline
AU - Hernandez, Dena
AU - Hillege, Hans
AU - Ittermann, Till
AU - Kent, Jack W.
AU - Kolcic, Ivana
AU - Laatikainen, Tiina
AU - Lahti, Jari
AU - Leach, Irene Mateo
AU - Lee, Christine G.
AU - Lee, Jong Young
AU - Liu, Tian
AU - Liu, Youfang
AU - Lobbens, Stéphane
AU - Loh, Marie
AU - Lyytikaïnen, Leo Pekka
AU - Medina-Gomez, Carolina
AU - Michaëlsson, Karl
AU - Nalls, Mike A.
AU - Nielson, Carrie M.
AU - Oozageer, Laticia
AU - Pascoe, Laura
AU - Paternoster, Lavinia
AU - Polašek, Ozren
AU - Ripatti, Samuli
AU - Sarzynski, Mark A.
AU - Shin, Chan Soo
AU - Naranäiä, Nina Smolej
AU - Spira, Dominik
AU - Srikanth, Priya
AU - Steinhagen-Thiessen, Elisabeth
AU - Sung, Yun Ju
AU - Swart, Karin M.A.
AU - Taittonen, Leena
AU - Tanaka, Toshiko
AU - Tikkanen, Emmi
AU - Van Der Velde, Nathalie
AU - Van Schoor, Natasja M.
AU - Verweij, Niek
AU - Wright, Alan F.
AU - Yu, Lei
AU - Zmuda, Joseph M.
AU - Eklund, Niina
AU - Forrester, Terrence
AU - Grarup, Niels
AU - Jackson, Anne U.
AU - Kristiansson, Kati
AU - Kuulasmaa, Teemu
AU - Kuusisto, Johanna
AU - Lichtner, Peter
AU - Luan, Jian'an
AU - Mahajan, Anubha
AU - Männistö, Satu
AU - Palmer, Cameron D.
AU - Ried, Janina S.
AU - Scott, Robert A.
AU - Stancáková, Alena
AU - Wagner, Peter J.
AU - Demirkan, Ayse
AU - Döring, Angela
AU - Gudnason, Vilmundur
AU - Kiel, Douglas P.
AU - Kühnel, Brigitte
AU - Mangino, Massimo
AU - McKnight, Barbara
AU - Menni, Cristina
AU - O'Connell, Jeffrey R.
AU - Oostra, Ben A.
AU - Shuldiner, Alan R.
AU - Song, Kijoung
AU - Vandenput, Liesbeth
AU - Van Duijn, Cornelia M.
AU - Vollenweider, Peter
AU - White, Charles C.
AU - Boehnke, Michael
AU - Boettcher, Yvonne
AU - Cooper, Richard S.
AU - Forouhi, Nita G.
AU - Gieger, Christian
AU - Grallert, Harald
AU - Hingorani, Aroon
AU - Jørgensen, Torben
AU - Jousilahti, Pekka
AU - Kivimaki, Mika
AU - Kumari, Meena
AU - Laakso, Markku
AU - Langenberg, Claudia
AU - Linneberg, Allan
AU - Luke, Amy
AU - McKenzie, Colin A.
AU - Palotie, Aarno
AU - Pedersen, Oluf
AU - Peters, Annette
AU - Strauch, Konstantin
AU - Tayo, Bamidele O.
AU - Wareham, Nicholas J.
AU - Bennett, David A.
AU - Bertram, Lars
AU - Blangero, John
AU - Blüher, Matthias
AU - Bouchard, Claude
AU - Campbell, Harry
AU - Cho, Nam H.
AU - Cummings, Steven R.
AU - Czerwinski, Stefan A.
AU - Demuth, Ilja
AU - Eckardt, Rahel
AU - Eriksson, Johan G.
AU - Ferrucci, Luigi
AU - Franco, Oscar H.
AU - Froguel, Philippe
AU - Gansevoort, Ron T.
AU - Hansen, Torben
AU - Harris, Tamara B.
AU - Hastie, Nicholas
AU - Heliövaara, Markku
AU - Hofman, Albert
AU - Jordan, Joanne M.
AU - Jula, Antti
AU - Kähönen, Mika
AU - Kajantie, Eero
AU - Knekt, Paul B.
AU - Koskinen, Seppo
AU - Kovacs, Peter
AU - Lehtimäki, Terho
AU - Lind, Lars
AU - Liu, Yongmei
AU - Orwoll, Eric S.
AU - Osmond, Clive
AU - Perola, Markus
AU - Pérusse, Louis
AU - Raitakari, Olli T.
AU - Rankinen, Tuomo
AU - Rao, D. C.
AU - Rice, Treva K.
AU - Rivadeneira, Fernando
AU - Rudan, Igor
AU - Salomaa, Veikko
AU - Sørensen, Thorkild I.A.
AU - Stumvoll, Michael
AU - Tönjes, Anke
AU - Towne, Bradford
AU - Tranah, Gregory J.
AU - Tremblay, Angelo
AU - Uitterlinden, André G.
AU - Van Der Harst, Pim
AU - Vartiainen, Erkki
AU - Viikari, Jorma S.
AU - Vitart, Veronique
AU - Vohl, Marie Claude
AU - Völzke, Henry
AU - Walker, Mark
AU - Wallaschofski, Henri
AU - Wild, Sarah
AU - Wilson, James F.
AU - Yengo, Loïc
AU - Bishop, D. Timothy
AU - Borecki, Ingrid B.
AU - Chambers, John C.
AU - Cupples, L. Adrienne
AU - Dehghan, Abbas
AU - Deloukas, Panos
AU - Fatemifar, Ghazaleh
AU - Fox, Caroline
AU - Furey, Terrence S.
AU - Franke, Lude
AU - Han, Jiali
AU - Hunter, David J.
AU - Karjalainen, Juha
AU - Karpe, Fredrik
AU - Kaplan, Robert C.
AU - Kooner, Jaspal S.
AU - McCarthy, Mark I.
AU - Murabito, Joanne M.
AU - Morris, Andrew P.
AU - Bishop, Julia A.N.
AU - North, Kari E.
AU - Ohlsson, Claes
AU - Ong, Ken K.
AU - Prokopenko, Inga
AU - Richards, J. Brent
AU - Schadt, Eric E.
AU - Spector, Tim D.
AU - Widén, Elisabeth
AU - Willer, Cristen J.
AU - Yang, Jian
AU - Ingelsson, Erik
AU - Mohlke, Karen L.
AU - Hirschhorn, Joel N.
AU - Pospisilik, John Andrew
AU - Zillikens, M. Carola
AU - Lindgren, Cecilia
AU - Kilpelaïnen, Tuomas Oskari
AU - Loos, Ruth J.F.
N1 - Funding Information: A full list of acknowledgements can be found in the Supplementary Notes. This work was supported by the following: Aase and Ejner Danielsens Foundation; Academy of Finland; Agency for Health Care Policy Research; Ahokas Foundation; ALFEDIAM; ALK-Abelló A/S (Hørsholm, Denmark); Althingi (the Icelandic Parliament); ANR (‘Agence Nationale de la 359 Recherche’); American Heart Association; Ardix Medical; Arthritis Research UK; Association Diabéte Risque Vasculaire, the Fédération Francaise de Cardiologie; AstraZeneca; Australian Research Council; Bayer Diagnostics; BBSRC; Becton Dickinson; BMBF (DEEP); Boehringer Ingelheim Foundation; Boston University School of Medicine; British Heart Foundation; British Skin Foundation; Canadian Institutes of Health Research; Cancer Research UK; Cardionics; Centers for Disease Control and Prevention/Association of Schools of Public Health; Chief Scientist Office of the Scottish Government; Cohortes Santé TGIR; CMSB; CPER (‘Contrat de Projets État-Région’); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research; Danish Medical Research Council; Department of Health, UK; Deutsche Forschungsgemeinschaft; Deutshe Forschungsgemeinschaft (SFB992); DHFD (Diabetes Hilfs- und Forschungsfonds Deutschland); Diabetes UK; Dutch Dairy Association (NZO); Dutch Kidney Foundation; Dutch Inter University Cardiology Institute Netherlands (ICIN); Emil Aaltonen Foundation; ENGAGE consortium; Food Standards Agency, UK; Erasmus Medical Center; Erasmus University; Estonian Government; European Commission; European Community’s Seventh Framework Programme; European Research Council; European Research Council (ERC-StG- 281641); European Union framework program 6 EUROSPAN project; European Union; European Union (EU_FP7_NoE ‘Epigenesys’); Faculty of Biology and Medicine of Lausanne; Federal State of Mecklenburg-West Pomerania; Federal Ministry of Education and Research (German Obesity Biomaterial Bank); Finnish Cardiovascular Research Foundation; Finnish Centre for Pensions; Finnish Cultural Foundation; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Foundation for Pediatric Research; Finnish Special Governmental Subsidy for Health Sciences; Finska Läkaresällskapet; Folkhälsan Research Foundation; German Bundesministerium fuer Forschung und Technology; German Diabetes Association; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); German Research Council; GlaxoSmithKline; Göran Gustafsson Foundation; Health and Safety Executive, UK; Helmholtz Zentrum Mu¨nchen—German Research Center for Environmental Health; Hjartavernd (the Icelandic Heart Association); Illinois Department of Public Health; INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé); Integrated Research and Treatment Centre (IFB); Juho Vainio Foundation; John D and Catherine T MacArthur Foundation Research Networks; John W. Barton Sr Chair in Genetics and Nutrition; Kompetenznetz Adipositas; King’s College London; Knut och Alice Wallenberg Foundation; Kuopio, Tampere and Turku University Hospital Medical Funds; Kuopio University Hospital; La Fondation de France; Li Ka Shing Foundation; Liv och Ha¨lsa; Local Government Pensions Institution (KEVA); Ludwig-Maximilians- Universita¨t; Lundbeck Foundation; Lundberg Foundation; Max-Planck Institute; Medical Research Council, UK; MEKOS Laboratories Denmark; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs and Social Ministry of the Federal State of Mecklenburg-West Pomerania; Ministry of Economic Affairs, Agriculture and Innovation, The Netherlands; Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport of the Republic of Croatia; MRC Centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); MRC-GlaxoSmithKline; MRC Human Genetics Unit; Munich Center of Health Sciences (MC Health); Municipality of Rotterdam; National Center for Advancing Translational Sciences, CTSI; National Center for Research Resources (NCRR); National Genome Research Institute, Korean Center for Disease Control and Prevention; National Heart Lung and Blood Institute (NHLBI); National Heart, Lung and Blood Institute’s Framingham Heart Study; National Institute for Health and Welfare (THL); National Institute for Health Research (NIHR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health; National Center for Advancing Translational Sciences; National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC); National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA); Netherlands Consortium Healthy Ageing (NCHA); Netherlands Genomics Initiative (NGI); Netherlands Heart Foundation; Netherlands Organisation for Scientific Research (NWO); Netherlands Organization for the Health Research and Development (ZonMw); Novo Nordisk; Novo Nordisk Foundation; ONIVINS; Orion-Farmos Research Foundation; Paavo Nurmi Foundation; Pierre Fabre; Research Centre for Prevention and Health, the Capital Region of Denmark; Research Institute for Diseases in the Elderly (RIDE); Research into Ageing, UK; Roche; Royal Swedish Academy of Science; Russian Foundation for Basic Research; Sanger Institute; Samfundet Folkhälsan; SFD (‘Sociéte Francophone du 358 Diabété); Siemens Healthcare; Signe and Ane Gyllenberg Foundation; Sigrid Jusélius Foundation; Social Insurance Institution of Finland (KELA); State of Bavaria; Stroke Association, UK; Swedish Diabetes Foundation; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Research Council; Swedish Research Council for Infrastructures; Swiss National Science Foundation; Sylvia & Charles Viertel Charitable Foundation; Tampere Tuberculosis Foundation; Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar So¨derberg’s Foundation; Translational Genomics Research Institute; Unilever UK; University Cancer Research Fund at UNC Chapel Hill; University of Eastern Finland; University of Maryland General Clinical Research Center; Uppsala University; Uppsala University Hospital; USDA National Institute of Food and Agriculture; VA Clinical Science Research and Development; Velux Foundation; VU University Medical Center; Wageningen University; Wellcome Trust.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (Po5108), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
AB - To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (Po5108), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
UR - http://www.scopus.com/inward/record.url?scp=84965156172&partnerID=8YFLogxK
U2 - 10.1038/ncomms10495
DO - 10.1038/ncomms10495
M3 - Article
C2 - 26833246
AN - SCOPUS:84965156172
SN - 2041-1723
VL - 7
JO - Nature communications
JF - Nature communications
M1 - 10495
ER -