Abstract
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. 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 traits2. In an expanded genome-wide association meta-analysis 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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References
Godfrey, K.M. & Barker, D.J. Fetal nutrition and adult disease. Am. J. Clin. Nutr. 71, 1344S–1352S (2000).
Freathy, R.M. et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat. Genet. 42, 430–435 (2010).
Zhao, J. et al. Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene. Diabetes 58, 2414–2418 (2009).
Andersson, E.A. et al. Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight. Diabetologia 53, 1908–1916 (2010).
Freathy, R.M. et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes 58, 1428–1433 (2009).
Hattersley, A.T. & Tooke, J.E. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet 353, 1789–1792 (1999).
Dupuis, J. et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet. 42, 105–116 (2010).
Saxena, R. et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat. Genet. 42, 142–148 (2010).
Strawbridge, R.J. et al. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes 60, 2624–2634 (2011).
Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat. Genet. 39, 770–775 (2007).
Metzger, B.E. et al. Hyperglycemia and adverse pregnancy outcomes. N. Engl. J. Med. 358, 1991–2002 (2008).
Freathy, R.M. et al. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups. Diabetes 59, 2682–2689 (2010).
Hattersley, A.T. et al. Mutations in the glucokinase gene of the fetus result in reduced birth weight. Nat. Genet. 19, 268–270 (1998).
Johnson, A.D. et al. Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension 57, 903–910 (2011).
Lenfant, C. Low birth weight and blood pressure. Metabolism 57 (suppl. 2), S32–S35 (2008).
Gamborg, M. et al. Birth weight and systolic blood pressure in adolescence and adulthood: meta-regression analysis of sex- and age-specific results from 20 Nordic studies. Am. J. Epidemiol. 166, 634–645 (2007).
Ehret, G.B. et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478, 103–109 (2011).
Ikram, M.A. et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nat. Genet. 44, 539–544 (2012).
Taal, H.R. et al. Common variants at 12q15 and 12q24 are associated with infant head circumference. Nat. Genet. 44, 532–538 (2012).
Sovio, U. et al. Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966. PLoS Genet. 5, e1000409 (2009).
Lango Allen, H. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832–838 (2010).
Voight, B.F. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet. 42, 579–589 (2010).
Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906–913 (2007).
Li, Y., Willer, C.J., Ding, J., Scheet, P. & Abecasis, G.R. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet. Epidemiol. 34, 816–834 (2010).
Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
Aulchenko, Y.S., Ripke, S., Isaacs, A. & van Duijn, C.M. GenABEL: an R library for genome-wide association analysis. Bioinformatics 23, 1294–1296 (2007).
Aulchenko, Y.S., Struchalin, M.V. & van Duijn, C.M. ProbABEL package for genome-wide association analysis of imputed data. BMC Bioinformatics 11, 134 (2010).
Krestyaninova, M. et al. A System for Information Management in BioMedical Studies—SIMBioMS. Bioinformatics 25, 2768–2769 (2009).
Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997–1004 (1999).
Willer, C.J., Li, Y. & Abecasis, G.R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).
Mägi, R. & Morris, A.P. GWAMA: software for genome-wide association meta-analysis. BMC Bioinformatics 11, 288 (2010).
Yang, J. et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011).
Weedon, M.N. et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat. Genet. 40, 575–583 (2008).
Higgins, J.P. & Thompson, S.G. Quantifying heterogeneity in a meta-analysis. Stat. Med. 21, 1539–1558 (2002).
Altshuler, D. et al. The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat. Genet. 26, 76–80 (2000).
Grant, S.F. et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat. Genet. 38, 320–323 (2006).
Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445, 881–885 (2007).
Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336–1341 (2007).
Scott, L.J. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341–1345 (2007).
Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007).
Sandhu, M.S. et al. Common variants in WFS1 confer risk of type 2 diabetes. Nat. Genet. 39, 951–953 (2007).
Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nat. Genet. 39, 977–983 (2007).
Zeggini, E. et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat. Genet. 40, 638–645 (2008).
Rung, J. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat. Genet. 41, 1110–1115 (2009).
Prokopenko, I. et al. Variants in MTNR1B influence fasting glucose levels. Nat. Genet. 41, 77–81 (2009).
Kong, A. et al. Parental origin of sequence variants associated with complex diseases. Nature 462, 868–874 (2009).
Kooner, J.S. et al. Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nat. Genet. 43, 984–989 (2011).
Yamauchi, T. et al. A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Nat. Genet. 42, 864–868 (2010).
Weedon, M.N. et al. Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. Diabetes 54, 576–581 (2005).
Freathy, R.M. et al. Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals. Am. J. Hum. Genet. 80, 1150–1161 (2007).
Teslovich, T.M. et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713 (2010).
Speliotes, E.K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 42, 937–948 (2010).
Niklasson, A. et al. An update of the Swedish reference standards for weight, length and head circumference at birth for given gestational age (1977–1981). Acta Paediatr. Scand. 80, 756–762 (1991).
Acknowledgements
A complete list of acknowledgments is given in the Supplementary Note. Major funding for the research in this paper is provided by the Academy of Finland (project grants 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi), 209072, 129255, 104781, 120315, 129269, 1114194, 206374, 251360, 139900/24300796, Center of Excellence in Complex Disease Genetics and SALVE) and Biocentrum Helsinki; Arthritis Research UK; the Augustinus Foundation; the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL); the Biomedical Research Council, Singapore (BMRC 06/1/21/19/466); BIF: Boehringer Ingelheim Fonds (travel grant to A.T.); the British Heart Foundation; the C.G. Sundell Foundation; the Canadian Institutes of Health Research (grant MOP-82893); Cancer Research UK; the Chief Scientist Office of the Scottish Government; the Children's Hospital of Philadelphia (Institute Development Award); Conselleria de Sanitat Generalitat Valenciana; the Copenhagen Graduate School of Health Sciences; the Cotswold Foundation (Research Development Award); the Curtin University and Women and Infants Research Foundation; the Danish Health Insurance Societies (Health Fund); the Danish Medical Research Council; the Danish National Research Foundation; the Danish Pediatric Asthma Centre; the Danish Pharmacists' Fund; the Danish Strategic Research Council; the Darlington Trust; the Department of Health and Social Services in Northern Ireland; Deutsche Forschungsgemeinschaft (DFG); Diabetes Hilfs- und Forschungsfonds Deutschland (DHFD; travel grant to M. Stumvoll); Diabetes UK (grants RD08/0003704 and RD08/0003692); the Dunhill Medical Trust; the Dutch Asthma Foundation (grants 3.4.01.26, 3.2.06.022, 3.4.09.081 and 3.2.10.085CO); the Dutch Ministry of the Environment (EFRE): Europäische Fonds für Regionale Entwicklung (LIFE Child Obesity); the Egmont Foundation; the Else Kröner-Fresenius Foundation; the Emil Aaltonen Foundation (T.L.); the ENGAGE project and grant agreement HEALTH-F4-2007-201413; the Erasmus Medical Center; Erasmus University, Rotterdam; the European Commission (EURO-BLCS, Beta-JUDO, Framework 5 award QLG1-CT-2000-01643, GABRIEL (Integrated Program LSH-2004-1.2.5-1 contract 018996), framework programme 6 EUROSPAN project (contract LSHG-CT-2006-018947), Sixth Research, Technological Development (RTD) Framework Programme (Contract FOOD-CT-2005-007034) and Seventh Framework Programme (FP7/2007-2013)); the European Research Council (ERC Advanced; 230374); the European Science Foundation (ESF; EU/QLRT-2001-01254); the Exeter NHS Research and Development; Faculty of Biology and Medicine of Lausanne; the Finnish Foundation of Cardiovascular Research; the Finnish Cultural Foundation; the Finnish Innovation Fund Sitra; the Finnish Ministry of Education and Culture; the Finnish Ministry of Social Affairs and Health; the Finnish Social Insurance Institution; the Foundation for Paediatric Research; Fundació La Marató de TV3; Fundación Roger Torné; Generalitat de Catalunya–Interminesterial Council for Research and Technological Innovation (CIRIT; 1999SGR) 00241; the German Diabetes Association (A.T.); the German Bundesministerium fuer Forschung und Technology (grants 01 AK 803 A-H and 01 IG 07015 G); the German Research Foundation for the Clinical Research Group Atherobesity KFO 152 (KO3512/1 to A.K.); GlaxoSmithKline; the Hagedorn Research Institute; Instituto de Salud Carlos III (CB06/02/0041, FIS PI041436, PI081151, PI041705 and PS09/00432 and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647); the Interdisciplinary Centre for Clinical Research at the University of Leipzig (B27 to A.T. and M. Stumvoll); the Integrated Research and Treatment Centre (IFB) Adiposity Diseases; the Jackstädt-Foundation; the Juho Vainio Foundation; the Juvenile Diabetes Research Foundation International (JDRF); Kuopio, Tampere and Turku University Hospital Medical Funds (grant 5031343 to T.A. Lakka and grant 9M048 to T.L.); The Lundbeck Foundation; the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP); the March of Dimes Birth Defects Foundation (6-FY09-507); the MRC, UK (grants 74882, G0000934, G0601653, G0500539, G0600705, G0601261, G0600331, PrevMetSyn/SALVE PS0476 and MC-A760-5QX00); the Munich Center of Health Sciences (MC Health); the National Health and Medical Research Council of Australia (grants 403981 and 003209); the US National Human Genome Research Institute; the US National Institute of Allergy and Infectious Diseases; the US National Institute of Child Health and Human Development; the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the US National Institutes of Health (grants U01DK062418, U01HG004423, U01HG004446, U01HG004438, R01DK075787, 1R01HD056465-01A, R01D0042157-01A, DK078150, TW05596, HL085144, HD054501, RR20649, ES10126, DK56350 and Biomedical Research Centers funding); the Netherlands Bioinformatics Centre (NBIC) BioAssist (RK/2008.024); a National Heart, Lung, and Blood Institute (NHLBI) grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01); the NIH Genetic Association Information Network (GAIN); the NIH/National Institute of Mental Health (NIMH) (5R01MH63706:02 and MH081802); the Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); the Novo Nordisk Foundation Center for Basic Metabolic Research; the Center for Medical Systems Biology (CMSB; NWO Genomics); the Netherlands Organization for Scientific Research (NWO: Social Sciences (MaGW) and the 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, 40-0056-98-9032 and 912-03-031); the Paavo Nurmi Foundation; the Peninsula NIHR Clinical Research Facility; the Pharmacy Foundation of 1991; the PhD School of Molecular Metabolism University of Southern Denmark; the Raine Medical Research Foundation; the Royal Society; the Sigrid Juselius Foundation; South West NHS Research and Development; the Spanish Ministry of Science and Innovation (SAF2008-00357), Turku University Hospital; the Swiss National Science Foundation (33CSCO-122661); the Tampere Tuberculosis Foundation; the Telethon Institute for Child Health Research; the Turku University Foundation; the US Centers for Disease Control and Prevention; University Hospital Oulu, Biocenter, the University of Oulu (75617); the University of Bristol; the University of Potsdam; the University of Southampton; the University of Western Australia (UWA); the VU Institute for Health and Care Research (EMGO+) and the Neuroscience Campus Amsterdam (NCA); the Wellcome Trust (grants GR069224, WT088806, 068545/Z/02, 076467, 085301, 090532, 083270, 083948, 085541/Z/08/Z, WT089549 and WT083431MA); and the Yrjö Jahnsson Foundation.
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Discussion group (decided on analyses specific to the project): J.P.B., T.M.F., R.M.F. (co-lead/chair), S.F.A.G., M.H., V.W.V.J., M.-R.J., M.I.M., D.O.M.-K., C.E.P., I.P. (co-lead), N.J.T. and H.Y. Writing group (drafted and edited manuscript): T.M.F., R.M.F. (co-lead/chair), B.J.H., M.H. (co-lead), V.W.V.J., M.-R.J., M.I.M., D.O.M.-K., I.P., H.R.T., N.J.T. and H.Y. (co-lead). Meta-analyses and other key analyses: Stage 1, discovery meta-analysis: R.M.F. (lead), J. Heikkinen (data exchange), D.O.M.-K., I.P. and U.S. Stage 2, follow-up and overall meta-analysis: R.M.F., M.H. (co-lead), I.P. and H.Y. (co-lead). Sensitivity meta-analyses: R.M.F. and H.Y. (lead). Analyses of known type 2 diabetes, blood pressure and height loci (including ALSPAC mother-child pair analyses): R.M.F. (lead), D.A.L., N.J.T. and H.Y. Postnatal data analysis: D.L.C., R.M.F., M. Kaakinen, D.O.M.-K. (lead), E.T. and U.S. Trans-ancestry analyses and genotype risk score analysis: M.H. (lead), I.P. (chair), N.J.T., H.Y., (CHOP) J.P.B., H.H. and S.F.A.G., (CLHNS) Y.W. and K.L.M., (Generation R) H.R.T. and V.W.V.J., (MRC Keneba) B.J.H., A.J.F. and A.M.P., (SAUDI) D.O.M.-K., F.S.A. and B.F.M. and (SCORM) L.-K.G. and S.-M.S. Cohort -specific contributions: Project design: (B58C) E.H. and C.P.; (ALSPAC) D.A.L., G.D.S. and N.J.T.; (BBC) B.H. and M.I.M.; (CHOP) J.P.B., S.F.A.G., H.H. and J.Z.; (CLHNS) L.S.A. and K.L.M.; (COLAUS) P.V.; (COPSAC-2000) H.B.; (COPSAC-REGISTRY) H.B. and K.B.; (DNBC) M.M.; (EFSOCH) T.M.F. and A.T.H.; (EPIC and EPIC-Norfolk) K.K.O.; (Generation R) A.H., V.W.V.J. and D.O.M.-K.; (HBCS) J.G.E.; (HCS) C.C.; (HELENA) F. Gottrand and L.A.M.; (INMA) X.E.; (Leipzig-Kids) A.K. and W.K.; (LISAplus and GINIplus) J. Heinrich; (MRC Keneba) A.J.F., B.J.H. and A.M.P.; (NFBC1966 and NFBC1986) M.-R.J. and U.S.; (NTR) D.I.B.; (ORCADES) J.F.W.; (PANIC) T.A.L.; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (RAINE) J.P.N. and C.E.P.; (SAUDI) F.S.A. and B.F.M.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) M. Stumvoll and A.T.; (STRIP) H.N., O.T.R. and O.S.; (SWS) K.M.G. and H.M.I.; (TEENAGE) G.V.D. and I.N.; (YF) T.L. and J.S.V.; and (Young Hearts Project) C.A.G.B. Sample collection and phenotyping: (B58C) D.J.B., E.H. and C.P.; (ALSPAC) D.A.L. and G.D.S.; (BBC) B.H., T.P. and T.S.; (CHOP) H.H.; (CLHNS) L.S.A. and C.W.K.; (COLAUS) P.V.; (COPSAC-2000) H.B., L.P. and N.H.V.; (COPSAC-REGISTRY) H.B., K.B., M.V.H., D.M.H. and E.K.-M.; (DNBC) B.F., F. Geller and M.M.; (EFSOCH) A.T.H., B.A.K. and B.M.S.; (EPIC and EPIC-Norfolk) K.K.O.; (ERF) B.A.O. and C.M.v.D.; (Generation R) A.H., V.W.V.J., D.O.M.-K. and H.R.T.; (GoDARTS) E.R.P.; (HBCS) J.G.E.; (HELENA) F. Gottrand and L.A.M.; (INMA) M.G.; (Inter99) T.H., T.J., O.P., A.V. and D.R.W.; (Leipzig-Kids) A.K. and W.K.; (LISAplus and GINIplus) C.F.; (MRC Keneba) A.J.F.; (NFBC1966 and NFBC1986) M.-R.J., M. Kaakinen and A.P.; (NTR) D.I.B., E.J.C.d.G., J.M.V. and G.W.; (ORCADES) J.F.W.; (PANIC) T.O.K., T.A.L. and V. Lindi; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (Project Viva) M.W.G.; (RAINE) J.P.N. and C.E.P.; (SAUDI) A.A.-O., B.F.M. and D.M.M.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) M. Stumvoll and A.T.; (STRIP) H.N., O.T.R. and O.S.; (SWS) K.M.G.; (TEENAGE) C.K.-G. and I.N.; (YF) T.L. and J.S.V.; and (Young Hearts Project) C.A.G.B. Genotyping: (B58C and B58C-Replication) A.J.B., C.J.G., M.I.M. and N.R.R.; (ALSPAC) J.P.K., G.M. and S.M.R.; (BBC) A.J.B., B.H., M.I.M., T.P., N.R.R. and T.S.; (CHOP) S.F.A.G. and H.H.; (COPSAC-REGISTRY) M.V.H. and D.M.H.; (EFSOCH) T.M.F. and R.M.F.; (EPIC and EPIC-Norfolk) R.J.F.L., N.J.W. and K.K.O.; (ERF) B.A.O. and C.M.v.D.; (Generation R) F.R. and A.G.U.; (GoDARTS) K.Z.; (HBCS) E.W.; (HCS) J.W.H.; (HELENA) J.D. and A. Meirhaeghe; (INMA) M.B.; (Inter99) E.A.A., T.H. and M.N.H.; (Leipzig-Kids) A.K.; (LISAplus and GINIplus) N.K. and C.M.T.T.; (MRC Keneba) B.J.H.; (NFBC1966 and NFBC1986) A.I.F.B., J.L.B., P.F. and M.I.M.; (NTR) J.-J.H.; (ORCADES) J.F.W.; (PANIC) T.A.L. and V. Lindi; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (Project Viva) J.N.H. and R.M.S.; (RAINE) J.P.N. and C.E.P.; (SAUDI) B.F.M. and D.M.M.; (SCORM) S.-M.S.; (SORBS) M. Stumvoll; (STRIP) O.T.R.; (SWS) J.W.H.; (TEENAGE) A.J.B., C.J.G., M.I.M. and N.R.R.; (YF) T.L.; and (Young Hearts Project) P.A. and A. Meirhaeghe. Statistical analysis: (B58C) D.J.B.; (B58C-Replication) M.H.; (ALSPAC) D.M.E., B.S.P. and N.J.T.; (BBC) B.H., M.H., T.P. and T.S.; (CHOP) J.P.B., S.F.A.G. and H.Z.; (CLHNS) Y.W.; (COLAUS) Z.K.; (COPSAC-2000) E.K.-M.; (COPSAC-REGISTRY) E.K.-M.; (DNBC) B.F. and F. Geller; (EFSOCH) R.M.F. and H.Y.; (EPIC and EPIC-Norfolk) M.d.H. and J.H.Z.; (ERF) A.I. and E.M.v.L.; (Generation R) D.O.M.-K. and H.R.T.; (GoDARTS) E.R.P. and K.Z.; (HBCS) D.L.C.; (HCS) K.A.J.; (HELENA) A. Meirhaeghe; (INMA) M.B.; (Inter99) E.A.A. and M.N.H.; (Leipzig-Kids) A. Mahajan; (LISAplus and GINIplus) E.T.; (MRC Keneba) A.J.F. and B.J.H.; (NFBC1966 and NFBC1986) P.C., S.D., M.H., M. Kaakinen, I.P., S.S. and U.S.; (NTR) J.-J.H.; (ORCADES) M. Kirin; (PANIC) V. Lindi; (PIAMA) M. Kerkhof; (Project Viva) M.W.G., J.N.H. and R.M.S.; (RAINE) N.M.W.; (SAUDI) D.O.M.-K.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) V. Lagou and I.P.; (STRIP) O.T.R. and M. Saarinen; (SWS) S.J.B. and H.M.I.; (TEENAGE) I.N. and M.H.; (YF) D.L.C. and E.W.; and (Young Hearts Project) P.A. and A. Meirhaeghe.
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Horikoshi, M., Yaghootkar, H., Mook-Kanamori, D. et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet 45, 76–82 (2013). https://doi.org/10.1038/ng.2477
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DOI: https://doi.org/10.1038/ng.2477
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