Rachel M. Freathy, Dennis O. Mook-Kanamori, Ulla Sovio, Inga Prokopenko, Nicholas J. Timpson, Diane J Berry, Nicole M. Warrington, Elisabeth Widen, Jouke Jan Hottenga, Marika Kaakinen, Leslie A. Lange, Jonathan P. Bradfield, Marjan Kerkhof, Julie A. Marsh, Reedik Mägi, Chih-Mei Chen, Helen N. Lyon, Mirna Kirin, Linda S. Adair, Yurii S. Aulchenko, Amanda J. Bennett, Judith B. Borja, Nabila Bouatia-Naji, Pimphen Charoen, Lachlan J.M. Coin, Diana L. Cousminer, Eco J.C. De Geus, Panos Deloukas, Paul Elliott, David M. Evans, Philippe Froguel, Beate Glaser, Christopher J. Groves, Anna-Liisa Hartikainen, Neelam Hassanali, Joel N. Hirschhorn, Albert Hofman, Jeff M.P. Holly, Elina Hyppönen, Stavroula Kanoni, Bridget A. Knight, Jaana Laitinen, Cecilia M. Lindgren, Wendy L. McArdle, Paul F. O'Reilly, Craig E. Pennell, Dirkje S. Postma, Anneli Pouta, Adaikalavan Ramasamy, Nigel W. Rayner, Susan M. Ring, Fernando Rivadeneira, Beverley M. Shields, David P. Strachan, Ida Surakka, Anja Taanila, Carla Tiesler, Andre G. Uitterlinden, Cornelia M. Van Duijn, Alet H. Wijga, Gonneke Willemsen, Haitao Zhang, Jianhua Zhao, James F. Wilson, Eric A.P. Steegers, Andrew T. Hattersley, Johan G. Eriksson, Leena Peltonen, Karen L. Mohlke, Struan F.A. Grant, Hakon Hakonarson, Gerard H. Koppelman, George V Dedoussis, Joachim Heinrich, Matthew W. Gillman, Lyle J. Palmer, Timothy M. Frayling, Dorret I. Boomsma, George Davey Smith, Chris Power, Vincent W.V. Jaddoe, Marjo-Riitta Jarvelin, Mark I. McCarthy
To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 × 10 35) and rs9883204 in ADCY5 (P = 7 × 10 15) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113g (95% CI 89-137g) lighter at birth than the 24% with zero or one alleles (P trend = 7 × 10 30). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy. © 2010 Nature America, Inc. All rights reserved.
Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, United Kingdom; Department of Pediatrics, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Generation R Study, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, United Kingdom; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Medical Research Council (MRC), Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Bristol, United Kingdom; Centre for Paediatric Epidemiology and Biostatistics, MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom; Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Perth, WA, Australia; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Institute of Health Sciences, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Genetics, University of North Carolina, Chapel Hill, NC, United States; Center for Applied Genomics, Children's Hospital of Philadelphia, PA, United States; Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Helmholtz Zentrum Muenchen, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Germany; Ludwig-Maximilians University of Munich, Dr. von Hauner Children's Hospital, Munich, Germany; Division of Genetics, Program in Genomics, Children's Hospital, Boston, MA, United States; Department of Pediatrics, Harvard Medical School, Boston, MA, United States; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom; Department of Nutrition, University of North Carolina, Chapel Hill, NC, United States; Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Centre National de la Recherche Scientifique, UMR 8199, Institute of Biology, Lille, France; Lille Nord de France University, Lille, France; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Genomic Medicine, Hammersmith Hospital, Imperial College London, London, United Kingdom; Children of the Nineties, Department of Social Medicine, University of Bristol, Oakfield Grove, Bristol, United Kingdom; Institute of Clinical Medicine, University of Oulu, Oulu, Finland; Program in Medical and Population Genetics, Broad Institute of Massachusetts, Institute of Technology and Harvard, Cambridge, MA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States; Division of Endocrinology, Children's Hospital, Boston, MA, United States; Department of Clinical Science at North Bristol, University of Bristol, Southmead Hospital, Bristol, United Kingdom; Department of Dietetics-Nutrition, Harokopio University, Greece; Peninsula National Institute for Health Research (NIHR), Clinical Research Facility, University of Exeter, Exeter, Barrack Road, United Kingdom; Oulu Regional Institute of Occupational Health, Oulu, Finland; Department of Social Medicine, University of Bristol, Oakfield House, Bristol, United Kingdom; School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia; Department of Pulmonology, University Medical Center, University of Groningen, Groningen, Netherlands; National Institute of Health and Welfare, Oulu, Finland; Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands; Division of Community Health Sciences, St. george'S, University of London, London, United Kingdom; Centre for Prevention and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands; Division of Human Genetics, Children's Hospital of Philadelphia, PA, United States; Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, Netherlands; Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland; Department of General Practice, University of Helsinki, Helsinki, Finland; Folkhälsan Research Centre, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Broad Institute of Harvard, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States; Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center, Groningen, Netherlands; Obesity Prevention Program, Department of Population Medicine, Harvard Medical School, Boston, MA, United States; Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
