Journal
NATURE GENETICS
Volume 42, Issue 5, Pages 430-U73Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.567
Keywords
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Categories
Funding
- Academy of Finland [104781, 120315, 209072, 129255, 129287]
- Biocentrum Helsinki
- Biocenter, University of Oulu, Finland
- British Heart Foundation
- Canadian Institutes of Health Research [MOP 82893]
- Center for Medical Systems Biology
- Centre for Neurogenomics and Cognitive Research (CNCR-VU) [EU/QLRT-2001-01254]
- Chief Scientist Office of the Scottish Government
- Children's Hospital of Philadelphia
- Coca-Cola Hellas
- Cotswold Foundation
- Darlington Trust
- Department of Health's National Institute of Health Research UK
- Diabetes UK [RD08/0003704]
- Dutch Asthma Foundation
- Dutch Ministry of the Environment
- Erasmus Medical Center Rotterdam
- Erasmus University Rotterdam
- European Commission [QLG1-CT-2000-01643]
- European Community's Seventh Framework Programme [FP7/2007-2013]
- ENGAGE project [HEALTH-F4-2007-201413]
- European Union [LSHG-CT-2006-018947]
- Exeter National Health Service Research and Development
- Friedrich-Schiller University Jena
- Genetic Association Information Network
- Healthway Western Australia
- Helmholtz Zentrum Muenchen-German Research Center for Environment and Health
- Institute of Epidemiology Neuherberg
- Institut fur Umweltmedizinische Forschung (IUF) Dusseldorf
- Juvenile Diabetes Research Foundation International
- German Federal Ministry of Education and Research [FKZ: 01GI0826]
- Marien-Hospital Wesel
- MRC UK [G0601261, G0600705, G0500539, G0000934, G0601653]
- Munich Center of Health Sciences (MCHEALTH)
- Municipal Health Service Rotterdam
- National Health and Medical Research Council of Australia [572613]
- National Human Genome Research Institute (US)
- National Institute of Allergy and Infectious Diseases (US)
- National Institute of Child Health and Human Development (US) [HD056465, HD034568, HD05450]
- National Institute of Diabetes and Digestive and Kidney Diseases (US) [DK075787, DK078150, DK56350]
- National Institute for Environmental Health Sciences (US) [ES10126]
- National Institute of Mental Health (US) [MH083268, MH63706]
- National Heart, Lung, and Blood Institute (US) [HL0876792, HL085144, HL068041]
- National Institutes of Health (US) (Fogarty International Center) [TW05596]
- National Institutes of Health (US) (National Center for Research Resources) [RR20649]
- National Public Health Institute, Helsinki, Finland
- Netherlands Organisation for Scientific Research (NWO)/Netherlands Organisation for Health Research and Development (ZonMw) [SPI 56-464-14192, 904-61-090, 904-61-193, 480-04-004, 400-05-717]
- Office of Population Studies Foundation, University of San Carlos, Philippines
- Peninsula NIHR Clinical Research Facility (UK)
- Raine Medical Research Foundation
- Rotterdam Homecare Foundation
- South West National Health Service Research and Development (UK) Spinoza
- St. Georg Hospital Leipzig
- Stichting Astmabestrijding
- Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR) Rotterdam
- Technical University Munich
- Telethon Institute for Child Health Research
- Type 1 Diabetes Genetics Consortium
- UFZ-Centre for Environmental Research Leipzig-Halle
- University Hospital Oulu Biocenter, University of Oulu, Finland
- University of Bristol
- University of Leipzig
- Wellcome Trust [085301, 068545/Z/02, 076113/B/04/Z, 085541/Z/08/Z, 89061/Z/09/Z]
- Western Australian DNA Bank
- Western Australian Genetic Epidemiology Resource
- Wind Over Water Foundation
- US National Institutes of Health [1R01DK075787]
- Career Scientist Award, Department of Health, UK
- UK Department of Health Policy Research Programme
- Netherlands Organization for Health Research [ZonMw 90700303]
- Wellcome Trust [085541/Z/08/Z] Funding Source: Wellcome Trust
- MRC [G0801056, G0400546, G0600331, G0800582, G0601653, G0500070, G0600705, G0000934, G0601261] Funding Source: UKRI
- Chief Scientist Office [CZB/4/710] Funding Source: researchfish
- Diabetes UK [08/0003692] Funding Source: researchfish
- Medical Research Council [G0801056, G0400546B, G0601653, G0600705, G0700704B, G0801056B, G0000934, G0400546, G9815508, G0600331, G0500070, G0601261, G0800582] Funding Source: researchfish
- National Institute for Health Research [PHCS/C4/4/016] Funding Source: researchfish
- Academy of Finland (AKA) [209072, 129287] Funding Source: Academy of Finland (AKA)
Ask authors/readers for more resources
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 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 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(1), providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes(2,3) 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, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P-trend = 7 x 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(4).
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