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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Momoko Horikoshi, Hanieh Yaghootkar, Dennis O. Mook-Kanamori, Ulla Sovio, H. Rob Taal, Branwen J. Hennig, Jonathan P. Bradfield, Beate St Pourcain, David M. Evans, Pimphen Charoen, Marika Kaakinen, Diana L. Cousminer, Terho Lehtimaki, Eskil Kreiner-Moller, Nicole M. Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J. Berry, Elisabeth Thiering, Thiemo Pfab, Sheila J. Barton, Beverley M. Shields, Marjan Kerkhof, Elisabeth M. van Leeuwen, Anthony J. Fulford, Zoltan Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T. Raitakari, Marie N. Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M. Salem, Karen A. Jameson, Kaixin Zhou, Dorota M. Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S. Adair, Fowzan S. Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Amanda J. Bennett, Alexandra I. F. Blakemore, Jessica L. Buxton, Jean Dallongeville, Shikta Das, Eco J. C. de Geus, Xavier Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M. Godfrey, Frederic Gottrand, Christopher J. Groves, Torben Hansen, Joel N. Hirschhorn, Albert Hofman, Mads V. Hollegaard, David M. Hougaard, Elina Hyppoenen, Hazel M. Inskip, Aaron Isaacs, Torben Jorgensen, Christina Kanaka-Gantenbein, John P. Kemp, Wieland Kiess, Tuomas O. Kilpelainen, Norman Klopp, Bridget A. Knight, Christopher W. Kuzawa, George McMahon, John P. Newnham, Harri Niinikoski, Ben A. Oostra, Louise Pedersen, Dirkje S. Postma, Susan M. Ring, Fernando Rivadeneira, Neil R. Robertson, Sylvain Sebert, Olli Simell, Torsten Slowinski, Carla M. T. Tiesler, Anke Toenjes, Allan Vaag, Jorma S. Viikari, Jacqueline M. Vink, Nadja Hawwa Vissing, Nicholas J. Wareham, Gonneke Willemsen, Daniel R. Witte, Haitao Zhang, Jianhua Zhao, James F. Wilson, Michael Stumvoll, Andrew M. Prentice, Brian F. Meyer, Ewan R. Pearson, Colin A. G. Boreham, Cyrus Cooper, Matthew W. Gillman, George V. Dedoussis, Luis A. Moreno, Oluf Pedersen, Maiju Saarinen, Karen L. Mohlke, Dorret I. Boomsma, Seang-Mei Saw, Timo A. Lakka, Antje Koerner, Ruth J. F. Loos, Ken K. Ong, Peter Vollenweider, Cornelia M. van Duijn, Gerard H. Koppelman, Andrew T. Hattersley, John W. Holloway, Berthold Hocher, Joachim Heinrich, Chris Power, Mads Melbye, Monica Guxens, Craig E. Pennell, Klaus Bonnelykke, Hans Bisgaard, Johan G. Eriksson, Elisabeth Widen, Hakon Hakonarson, Andre G. Uitterlinden, Anneli Pouta, Debbie A. Lawlor, George Davey Smith, Timothy M. Frayling, Mark I. McCarthy, Struan F. A. Grant, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Nicholas J. Timpson, Inga Prokopenko, Rachel M. Freathy

  • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

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Author:Momoko Horikoshi, Hanieh Yaghootkar, Dennis O. Mook-Kanamori, Ulla Sovio, H. Rob Taal, Branwen J. Hennig, Jonathan P. Bradfield, Beate St Pourcain, David M. Evans, Pimphen Charoen, Marika Kaakinen, Diana L. Cousminer, Terho Lehtimaki, Eskil Kreiner-Moller, Nicole M. Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J. Berry, Elisabeth Thiering, Thiemo Pfab, Sheila J. Barton, Beverley M. Shields, Marjan Kerkhof, Elisabeth M. van Leeuwen, Anthony J. Fulford, Zoltan Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T. Raitakari, Marie N. Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M. Salem, Karen A. Jameson, Kaixin Zhou, Dorota M. Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S. Adair, Fowzan S. Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Amanda J. Bennett, Alexandra I. F. Blakemore, Jessica L. Buxton, Jean Dallongeville, Shikta Das, Eco J. C. de Geus, Xavier Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M. Godfrey, Frederic Gottrand, Christopher J. Groves, Torben Hansen, Joel N. Hirschhorn, Albert Hofman, Mads V. Hollegaard, David M. Hougaard, Elina Hyppoenen, Hazel M. Inskip, Aaron Isaacs, Torben Jorgensen, Christina Kanaka-Gantenbein, John P. Kemp, Wieland Kiess, Tuomas O. Kilpelainen, Norman Klopp, Bridget A. Knight, Christopher W. Kuzawa, George McMahon, John P. Newnham, Harri Niinikoski, Ben A. Oostra, Louise Pedersen, Dirkje S. Postma, Susan M. Ring, Fernando Rivadeneira, Neil R. Robertson, Sylvain Sebert, Olli Simell, Torsten Slowinski, Carla M. T. Tiesler, Anke Toenjes, Allan Vaag, Jorma S. Viikari, Jacqueline M. Vink, Nadja Hawwa Vissing, Nicholas J. Wareham, Gonneke Willemsen, Daniel R. Witte, Haitao Zhang, Jianhua Zhao, James F. Wilson, Michael Stumvoll, Andrew M. Prentice, Brian F. Meyer, Ewan R. Pearson, Colin A. G. Boreham, Cyrus Cooper, Matthew W. Gillman, George V. Dedoussis, Luis A. Moreno, Oluf Pedersen, Maiju Saarinen, Karen L. Mohlke, Dorret I. Boomsma, Seang-Mei Saw, Timo A. Lakka, Antje Koerner, Ruth J. F. Loos, Ken K. Ong, Peter Vollenweider, Cornelia M. van Duijn, Gerard H. Koppelman, Andrew T. Hattersley, John W. Holloway, Berthold HocherGND, Joachim Heinrich, Chris Power, Mads Melbye, Monica Guxens, Craig E. Pennell, Klaus Bonnelykke, Hans Bisgaard, Johan G. Eriksson, Elisabeth Widen, Hakon Hakonarson, Andre G. Uitterlinden, Anneli Pouta, Debbie A. Lawlor, George Davey Smith, Timothy M. Frayling, Mark I. McCarthy, Struan F. A. Grant, Vincent W. V. Jaddoe, Marjo-Riitta Jarvelin, Nicholas J. Timpson, Inga Prokopenko, Rachel M. Freathy
DOI:https://doi.org/10.1038/ng.2477
ISSN:1061-4036 (print)
Parent Title (English):Nature genetics
Publisher:Nature Publ. Group
Place of publication:New York
Document Type:Article
Language:English
Year of first Publication:2013
Year of Completion:2013
Creating Corporation:MAGIC, Early Growth Genetics EGG
Release Date:2017/03/26
Volume:45
Issue:1
Pagenumber:10
First Page:76
Last Page:U115
Funder:Academy of Finland [126925, 121584, 124282, 129378, 117787, 41071, 209072, 129255, 104781, 120315, 129269, 1114194, 206374, 251360, 139900/24300796]; Biocentrum Helsinki; Arthritis Research UK; Augustinus Foundation; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL); Biomedical Research Council, Singapore [BMRC 06/1/21/19/466]; BIF: Boehringer Ingelheim Fonds; British Heart Foundation; C.G. Sundell Foundation; Canadian Institutes of Health Research [MOP-82893]; Cancer Research UK; Chief Scientist Office of the Scottish Government; Children's Hospital of Philadelphia (Institute Development Award); Conselleria de Sanitat Generalitat Valenciana; Copenhagen Graduate School of Health Sciences; Cotswold Foundation (Research Development Award); Curtin University and Women and Infants Research Foundation; Danish Health Insurance Societies (Health Fund); Danish Medical Research Council; Danish National Research Foundation; Danish Pediatric Asthma Centre; Danish Pharmacists' Fund; Danish Strategic Research Council; Darlington Trust; Department of Health and Social Services in Northern Ireland; Deutsche Forschungsgemeinschaft (DFG); Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD); Diabetes UK [RD08/0003704, RD08/0003692]; Dunhill Medical Trust; Dutch Asthma Foundation [3.4.01.26, 3.2.06.022, 3.4.09.081, 3.2.10.085CO]; Dutch Ministry of the Environment (EFRE); Europaische Fonds fur Regionale Entwicklung (LIFE Child Obesity); Egmont Foundation; Else Kroner-Fresenius Foundation; Emil Aaltonen Foundation; ENGAGE project [HEALTH-F4-2007-201413]; Erasmus Medical Center; Erasmus University, Rotterdam; European Commission [QLG1-CT-2000-01643, 018996, LSHG-CT-2006-018947, FOOD-CT-2005-007034]; European Research Council (ERC Advanced) [230374]; European Science Foundation (ESF) [EU/QLRT-2001-01254]; Exeter NHS Research and Development; Faculty of Biology and Medicine of Lausanne; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation; Finnish Innovation Fund Sitra; Finnish Ministry of Education and Culture; Finnish Ministry of Social Affairs and Health; Finnish Social Insurance Institution; Foundation for Paediatric Research; Fundacio La Marato de TV3; Fundacion Roger Torne; Generalitat de Catalunya-Interminesterial Council for Research and Technological Innovation (CIRIT) [(1999SGR) 00241]; German Diabetes Association; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; German Research Foundation for the Clinical Research Group Atherobesity [KO3512/1]; GlaxoSmithKline; Hagedorn Research Institute; Instituto de Salud Carlos III [CB06/02/0041, FIS PI041436, PI081151, PI041705, PS09/00432, FISFEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647]; Interdisciplinary Centre for Clinical Research at the University of Leipzig [B27]; Integrated Research and Treatment Centre (IFB) Adiposity Diseases; Jackstadt-Foundation; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International (JDRF); Kuopio, Tampere and Turku University Hospital Medical Funds [5031343, 9M048]; Lundbeck Foundation; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP); March of Dimes Birth Defects Foundation [6-FY09-507]; MRC, UK [74882, G0000934, G0601653, G0500539, G0600705, G0601261, G0600331, PrevMetSyn/SALVE PS0476, MC-A760-5QX00]; Munich Center of Health Sciences (MC Health); National Health and Medical Research Council of Australia [403981, 003209]; US National Human Genome Research Institute; US National Institute of Allergy and Infectious Diseases; US National Institute of Child Health and Human Development; US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); US National Institutes of Health [U01DK062418, U01HG004423, U01HG004446, U01HG004438, R01DK075787, 1R01HD056465-01A, R01D0042157-01A, DK078150, TW05596, HL085144, HD054501, RR20649, ES10126, DK56350]; Netherlands Bioinformatics Centre (NBIC) BioAssist [RK/2008.024]; National Heart, Lung, and Blood Institute (NHLBI) [5R01HL087679-02]; National Heart, Lung, and Blood Institute (NHLBI) through the STAMPEED program [1RL1MH083268-01]; NIH Genetic Association Information Network (GAIN); NIH/National Institute of Mental Health (NIMH) [5R01MH63706: 02, MH081802]; Rutgers University Cell and DNA Repository cooperative agreement [NIMH U24 MH068457-06]; Novo Nordisk Foundation Center for Basic Metabolic Research; Center for Medical Systems Biology (CMSB; NWO Genomics); Netherlands Organization for Scientific Research (NWO: Social Sciences (MaGW); Netherlands Organization for Health Research and Development (ZonMw) [Middelgroot-911-09-032, Spinozapremie 56-464-14192, 904-61-090, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 985-10-002, 40-005698- 9032, 912-03-031]; Paavo Nurmi Foundation; Peninsula NIHR Clinical Research Facility; Pharmacy Foundation of 1991; PhD School of Molecular Metabolism University of Southern Denmark; Raine Medical Research Foundation; Royal Society; Sigrid Juselius Foundation; South West NHS Research and Development; Spanish Ministry of Science and Innovation [SAF2008-00357]; Turku University Hospital; Swiss National Science Foundation [33CSCO-122661]; Tampere Tuberculosis Foundation; Telethon Institute for Child Health Research; Turku University Foundation; US Centers for Disease Control and Prevention; University Hospital Oulu, Biocenter, the University of Oulu [75617]; University of Bristol; University of Potsdam; University of Southampton; University of Western Australia (UWA); VU Institute for Health and Care Research (EMGO+); Neuroscience Campus Amsterdam (NCA); Wellcome Trust [GR069224, WT088806, 068545/Z/02, 076467, 085301, 090532, 083270, 083948, 085541/Z/08/Z, WT089549, WT083431MA]; Yrjo Jahnsson Foundation; Academy of Finland (Center of Excellence in Complex Disease Genetics); Academy of Finland (SALVE)
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Peer Review:Referiert