Letter | Published:

Genome-wide associations for birth weight and correlations with adult disease

Nature volume 538, pages 248252 (13 October 2016) | Download Citation

This article has been updated

Abstract

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

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Change history

  • 03 October 2016

    The Supplementary Information pdf was replaced and the description updated.

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Acknowledgements

Full acknowledgements and supporting grant details can be found in the Supplementary Information.

Author information

Author notes

    • Momoko Horikoshi
    • , Robin N. Beaumont
    • , Felix R. Day
    • , Nicole M. Warrington
    • , Marjolein N. Kooijman
    •  & Juan Fernandez-Tajes

    These authors contributed equally to this work.

    • Mads V. Hollegaard

    Deceased.

    • Andrew P. Morris
    • , Ken K. Ong
    • , Janine F. Felix
    • , Nicholas J. Timpson
    • , John R. B. Perry
    • , David M. Evans
    • , Mark I. McCarthy
    •  & Rachel M. Freathy

    These authors jointly supervised this work.

Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK

    • Momoko Horikoshi
    • , Juan Fernandez-Tajes
    • , Natalie R. van Zuydam
    • , Kyle J. Gaulton
    • , Anubha Mahajan
    • , Vasiliki Lagou
    • , Krina T. Zondervan
    • , Nilufer Rahmioglu
    • , Inga Prokopenko
    • , Neil R. Robertson
    • , Andrew P. Morris
    •  & Mark I. McCarthy
  2. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LE, UK

    • Momoko Horikoshi
    • , Natalie R. van Zuydam
    • , Amanda J. Bennett
    • , Neil R. Robertson
    • , Christopher J. Groves
    •  & Mark I. McCarthy
  3. Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK

    • Robin N. Beaumont
    • , Samuel E. Jones
    • , Katherine S. Ruth
    • , Marcus A. Tuke
    • , Jessica Tyrrell
    • , Andrew R. Wood
    • , Hanieh Yaghootkar
    • , Andrew T. Hattersley
    • , Timothy M. Frayling
    •  & Rachel M. Freathy
  4. MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK

    • Felix R. Day
    • , Claudia Langenberg
    • , Jian’an Luan
    • , Robert A. Scott
    • , Jing Hua Zhao
    • , Nicholas J. Wareham
    • , Ken K. Ong
    •  & John R. B. Perry
  5. The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4102, Australia

    • Nicole M. Warrington
    •  & David M. Evans
  6. School of Women’s and Infants’ Health, The University of Western Australia, Perth, Western Australia 6009, Australia

    • Nicole M. Warrington
    • , Carol A. Wang
    • , John P. Newnham
    •  & Craig E. Pennell
  7. The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 CE, the Netherlands

    • Marjolein N. Kooijman
    • , Carolina Medina-Gomez
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , André G. Uitterlinden
    • , Vincent W. V. Jaddoe
    •  & Janine F. Felix
  8. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 CE, the Netherlands

    • Marjolein N. Kooijman
    • , Elisabeth M. van Leeuwen
    • , Frank J. A. van Rooij
    • , Sara M. Willems
    • , Carolina Medina-Gomez
    • , Cornelia M. van Duijn
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , André G. Uitterlinden
    • , Vincent W. V. Jaddoe
    •  & Janine F. Felix
  9. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 CE, the Netherlands

    • Marjolein N. Kooijman
    • , Vincent W. V. Jaddoe
    •  & Janine F. Felix
  10. Department of Epidemiology Research, Statens Serum Institut, Copenhagen DK-2300, Denmark

    • Bjarke Feenstra
    • , Lisbeth Carstensen
    • , Frank Geller
    •  & Mads Melbye
  11. Department of Pediatrics, University of California San Diego, La Jolla, San Diego, California 92093, USA

    • Kyle J. Gaulton
  12. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2100, Denmark

    • Niels Grarup
    • , Tarunveer S. Ahluwalia
    • , Christian T. Have
    • , Emil V. R. Appel
    • , Cilius E. Fonvig
    • , Caecilie Trier
    • , Jens-Christian Holm
    • , Torben Hansen
    •  & Oluf Pedersen
  13. Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA

    • Jonathan P. Bradfield
    • , Frank D. Mentch
    • , Hakon Hakonarson
    •  & Struan F. A. Grant
  14. Population Health Research Institute, St George’s University of London, Cranmer Terrace, London SW17 0RE, UK

    • David P. Strachan
  15. Department of Clinical Epidemiology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands

    • Ruifang Li-Gao
    • , Hugoline G. de Haan
    • , Frits R. Rosendaal
    •  & Dennis O. Mook-Kanamori
  16. COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, 2820 Gentofte, Denmark

    • Tarunveer S. Ahluwalia
    • , Eskil Kreiner
    • , Johannes Waage
    • , Klaus Bønnelykke
    •  & Hans Bisgaard
  17. Steno Diabetes Center, Gentofte DK-2820, Denmark

    • Tarunveer S. Ahluwalia
  18. Department of Computational Biology, University of Lausanne, Lausanne 1011, Switzerland

    • Rico Rueedi
  19. Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland

    • Rico Rueedi
    •  & Zoltán Kutalik
  20. Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  21. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  22. Institute for Molecular Medicine, Finland (FIMM), University of Helsinki, Helsinki FI-00100, Finland

    • Diana L. Cousminer
    •  & Elisabeth Widén
  23. Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA

    • Diana L. Cousminer
    • , Hakon Hakonarson
    •  & Struan F. A. Grant
  24. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

    • Diana L. Cousminer
  25. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA

    • Ying Wu
    •  & Karen L. Mohlke
  26. Institute of Epidemiology I, Helmholtz Zentrum München- German Research Center for Environmental Health, 85764 Neuherberg, Germany

    • Elisabeth Thiering
    • , Carla M. T. Tiesler
    • , Marie Standl
    •  & Joachim Heinrich
  27. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, University of Munich Medical Center, 80337 Munich, Germany

    • Elisabeth Thiering
    •  & Carla M. T. Tiesler
  28. Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit, Amsterdam 1081 BT, the Netherlands

    • Jouke-Jan Hottenga
    • , Catharina E. M. van Beijsterveldt
    • , Gonneke Willemsen
    • , Eco J. C. N. de Geus
    •  & Dorret I. Boomsma
  29. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona 08003, Spain

    • Natalia Vilor-Tejedor
    • , Mariona Bustamante
    •  & Martine Vrijheid
  30. Universitat Pompeu Fabra (UPF), Barcelona 08002, Spain

    • Natalia Vilor-Tejedor
    • , Mariona Bustamante
    •  & Martine Vrijheid
  31. CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain

    • Natalia Vilor-Tejedor
    • , Mariona Bustamante
    • , Mario Murcia
    •  & Martine Vrijheid
  32. Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK

    • Peter K. Joshi
    • , Katharina E. Schraut
    • , Harry Campbell
    •  & James F. Wilson
  33. Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore 119077, Singapore

    • Eileen Tai Hui Boh
    • , Xu Wang
    • , Yik-Ying Teo
    •  & Seang-Mei Saw
  34. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK

    • Ioanna Ntalla
  35. Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens 17671, Greece

    • Ioanna Ntalla
    •  & George V. Dedoussis
  36. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20014, Finland

    • Niina Pitkänen
    • , Katja Pahkala
    •  & Olli T. Raitakari
  37. Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio FI-70211, Finland

    • Raimo Joro
    • , Mustafa Atalay
    • , Virpi Lindi
    •  & Timo A. Lakka
  38. KUL – University of Leuven, Department of Neurosciences, Leuven 3000, Belgium

    • Vasiliki Lagou
  39. Translational Immunology Laboratory, VIB, Leuven 3000, Belgium

    • Vasiliki Lagou
  40. Department of Preventive Medicine, Division of Biostatistics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

    • Michael Nodzenski
    •  & Denise M. Scholtens
  41. Institute of Cardiovascular & Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK

    • Louise A. Diver
    • , Scott M. MacKenzie
    •  & Eleanor Davies
  42. Endometriosis CaRe Centre, Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Oxford OX3 9DU, UK

    • Krina T. Zondervan
  43. Center for Genomic Regulation (CRG), Barcelona 08003, Spain

    • Mariona Bustamante
  44. Department of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne 1011, Switzerland

    • Pedro Marques-Vidal
    •  & Peter Vollenweider
  45. Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center, Barcelona 08034, Spain

    • Josep M. Mercader
    • , Sílvia Bonàs-Guarch
    • , Friman Sánchez
    •  & David Torrents
  46. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4000, Australia

    • Dale R. Nyholt
  47. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

    • Ronald C. W. Ma
    •  & Claudia H. T. Tam
  48. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China

    • Ronald C. W. Ma
  49. Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China

    • Ronald C. W. Ma
  50. Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China

    • Wing Hung Tam
  51. Department of Human Genetics and Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA

    • Santhi K. Ganesh
  52. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA

    • Po-Ru Loh
  53. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA

    • Po-Ru Loh
  54. European Centre for Environment and Human Health, University of Exeter, Truro TR1 3HD, UK

    • Jessica Tyrrell
  55. Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol BS8 2BN, UK

    • Lavinia Paternoster
    • , Susan M. Ring
    • , Gibran Hemani
    • , Thorkild I. A. Sørensen
    • , Debbie A. Lawlor
    • , George Davey Smith
    • , Nicholas J. Timpson
    • , David M. Evans
    •  & Rachel M. Freathy
  56. School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK

    • Lavinia Paternoster
    • , Susan M. Ring
    • , Gibran Hemani
    • , George McMahon
    • , Thorkild I. A. Sørensen
    • , Debbie A. Lawlor
    • , George Davey Smith
    • , Nicholas J. Timpson
    •  & David M. Evans
  57. Department of Genomics of Common Disease, School of Public Health, Imperial College London, London SW7 2AZ, UK

    • Inga Prokopenko
    •  & Sylvain Sebert
  58. IFB Adiposity Diseases, University of Leipzig, 04103 Leipzig, Germany

    • Peter Kovacs
    • , Michael Stumvoll
    •  & Antje Körner
  59. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK

    • Kalliope Panoutsopoulou
    •  & Eleftheria Zeggini
  60. FISABIO–Universitat Jaume I–Universitat de València, Joint Research Unit of Epidemiology and Environmental Health, Valencia 46020, Spain

    • Mario Murcia
  61. The Children’s Obesity Clinic, Department of Pediatrics, Copenhagen University Hospital Holbæk, Holbæk DK-4300, Denmark

    • Cilius E. Fonvig
    • , Caecilie Trier
    •  & Jens-Christian Holm
  62. Institute of Social and Preventive Medicine, Lausanne University Hospital (CHUV), Lausanne 1010, Switzerland

    • Zoltán Kutalik
  63. Danish Center for Neonatal Screening, Statens Serum Institute, Copenhagen DK-2300, Denmark

    • David M. Hougaard
    •  & Mads V. Hollegaard
  64. Department for Congenital Disorders, Statens Serum Institute, Copenhagen DK-2300, Denmark

    • David M. Hougaard
    •  & Mads V. Hollegaard
  65. Computer Sciences Department, Barcelona Supercomputing Center, Barcelona 08034, Spain

    • Friman Sánchez
  66. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain

    • David Torrents
  67. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015 CE, the Netherlands

    • Carolina Medina-Gomez
    • , Fernando Rivadeneira
    •  & André G. Uitterlinden
  68. BHF Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK

    • Rebecca M. Reynolds
    •  & Brian R. Walker
  69. Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA

    • William L. Lowe
  70. Medical Department, University of Leipzig, 04103 Leipzig, Germany

    • Anke Tönjes
    •  & Michael Stumvoll
  71. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio FI-70029, Finland

    • Timo A. Lakka
  72. Kuopio Research Institute of Exercise Medicine, Kuopio FI-70100, Finland

    • Timo A. Lakka
  73. Pediatric Research Center, Department of Women´s & Child Health, University of Leipzig, 04103 Leipzig, Germany

    • Wieland Kiess
    •  & Antje Körner
  74. Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark

    • Thorkild I. A. Sørensen
  75. Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen DK-2000, Denmark

    • Thorkild I. A. Sørensen
  76. Department of Pediatrics, Turku University Hospital, Turku 20521, Finland

    • Harri Niinikoski
  77. Department of Physiology, University of Turku, Turku 20014, Finland

    • Harri Niinikoski
  78. Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, Turku 20014, Finland

    • Katja Pahkala
  79. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland

    • Olli T. Raitakari
  80. Department of Statistics and Applied Probability, National University of Singapore, Singapore 117546, Singapore

    • Yik-Ying Teo
  81. Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore

    • Yik-Ying Teo
  82. Singapore Eye Research Institute, Singapore 168751, Singapore

    • Seang-Mei Saw
  83. Department of Clinical Medicine, University of Copenhagen, Copenhagen DK-2200, Denmark

    • Mads Melbye
    •  & Allan A. Vaag
  84. Department of Medicine, Stanford School of Medicine, Stanford, California 94305, USA

    • Mads Melbye
  85. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK

    • James F. Wilson
  86. EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam 1081 HV, the Netherlands

    • Eco J. C. N. de Geus
  87. Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C DK-1870, Denmark

    • Haja N. Kadarmideen
  88. Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu 90014, Finland

    • Sylvain Sebert
    •  & Marjo-Riitta Järvelin
  89. Biocenter Oulu, University of Oulu, Oulu 90014, Finland

    • Sylvain Sebert
    •  & Marjo-Riitta Järvelin
  90. School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, Western Australia 6000, Australia

    • Lawrence J. Beilin
  91. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Inner City Clinic, University Hospital Munich, Ludwig Maximilian University of Munich, 80336 Munich, Germany

    • Joachim Heinrich
  92. Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA

    • Linda S. Adair
  93. USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu City 6000, Philippines

    • Judith B. Borja
  94. Department of Nutrition and Dietetics, University of San Carlos, Cebu City 6000, Philippines

    • Judith B. Borja
  95. National Institute for Health and Welfare, Helsinki 00271, Finland

    • Johan G. Eriksson
  96. Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki 00014, Finland

    • Johan G. Eriksson
  97. Folkhälsan Research Center, Helsinki 00250, Finland

    • Johan G. Eriksson
  98. Department of Clinical Physiology, Tampere University Hopital, Tampere 33521, Finland

    • Mika Kähönen
  99. Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland

    • Mika Kähönen
  100. Division of Medicine, Turku University Hospital, Turku 20521, Finland

    • Jorma S. Viikari
  101. Department of Medicine, University of Turku, Turku 20014, Finland

    • Jorma S. Viikari
  102. Department of Public Health and Primary Care, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands

    • Dennis O. Mook-Kanamori
  103. 3Epidemiology Section, BESC Department, King Faisal Specialist Hospital and Research Centre, Riyadh 12713, Saudi Arabia

    • Dennis O. Mook-Kanamori
  104. Research Center for Prevention and Health Capital Region, Center for Sundhed, Rigshospitalet – Glostrup, Copenhagen University, Glostrup DK-2600, Denmark

    • Charlotta Pisinger
  105. Population, Policy and Practice, UCL Institute of Child Health, University College London, London WC1N 1EH, UK

    • Christine Power
    •  & Elina Hyppönen
  106. Centre for Population Health Research, School of Health Sciences, and Sansom Institute, University of South Australia, Adelaide, South Australia 5001, Australia

    • Elina Hyppönen
  107. South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia

    • Elina Hyppönen
  108. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

    • Hakon Hakonarson
    •  & Struan F. A. Grant
  109. Department of Epidemiology and Biostatistics, MRC–PHE Centre for Environment & Health, School of Public Health, Imperial College London, London SW7 2AZ, UK

    • Marjo-Riitta Järvelin
  110. Unit of Primary Care, Oulu University Hospital, Oulu 90220, Finland

    • Marjo-Riitta Järvelin
  111. Division of Endocrinology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA

    • Struan F. A. Grant
  112. Department of Endocrinology, Rigshospitalet, Copenhagen DK-2100, Denmark

    • Allan A. Vaag
  113. AstraZeneca, Innovative Medicines and Early Development | Early Clinical Development, Mölndal 431 83, Sweden

    • Allan A. Vaag
  114. Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK

    • Andrew P. Morris
  115. Estonian Genome Center, University of Tartu, Tartu 50090, Estonia

    • Andrew P. Morris
  116. Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK

    • Ken K. Ong
  117. Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Oxford OX3 7LE, UK

    • Mark I. McCarthy

Consortia

  1. CHARGE Consortium Hematology Working Group

    A list of consortium members appears in the Supplementary Information.

  2. Early Growth Genetics (EGG) Consortium

    A list of consortium members appears in the Supplementary Information.

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Contributions

Core analyses and writing: M.H., R.N.B., F.R.D., N.M.W., M.N.K., J.F.-T., N.R.v.Z., K.J.G., A.P.M., K.K.O., J.F.F., N.J.T., J.R.P., D.M.E., M.I.M., R.M.F. Statistical analysis in individual studies: M.H., R.N.B., F.R.D., N.M.W., M.N.K., B.F., N.G., J.P.B., D.P.S., R.L.-G., T.S.A., E.K., R.R., L.-P.L., D.L.C., Y.W., E.T., C.A.W., C.T.H., J.-J.H., N.V.-T., P.K.J., E.T.H.B., I.N., N.P., A.M., E.M.v.L., R.J., V.La., M.N., J.M.M., S.E.J., P.-R.L., K.S.R., M.A.T., J.T., A.R.W., H.Y., D.M.S., I.P., K.Pan., X.W., L.C., F.G., K.E.S., M.Mu., E.V.R.A., Z.K., S.B.-G., F.S., D.T., J.W., C.M.-G., N.R.R., E.Z., G.V.D., Y.-Y.T., H.N.K., A.P.M., J.F.F., N.J.T., J.R.P., D.M.E., R.M.F. GWAS look-up in unpublished datasets: K.T.Z., N.R., D.R.N., R.C.W.M., C.H.T.T., W.H.T., S.K.G., F.J.v.R. Sample collection and data generation in individual studies: F.R.D., M.N.K., B.F., N.G., J.P.B., D.P.S., R.L.-G., R.R., L.-P.L., J.-J.H., I.N., E.M.v.L., M.B., P.M.-V., A.J.B., L.P., P.K., M.A., S.M.W., F.G., C.E.v.B., G.W., E.V.R.A., C.E.F., C.T., C.M.T., M.Sta., Z.K., D.M.H., M.V.H., H.G.d.H., F.R.R., C.M.-G., S.M.R., G.H., G.M., N.R.R., C.J.G., C.L., J.L., R.A.S., J.H.Z., F.D.M., W.L.L.Jr, A.T., M.Stu., V.Li., T.A.L., C.M.v.D., A.K., T.I.S., H.N., K.Pah., O.T.R., E.Z., G.V.D., S.-M.S., M.Me., H.C., J.F.W., M.V., J.-C.H., T.H., S.S., L.J.B., J.P.N., C.E.P., L.S.A., J.B.B., K.L.M., J.G.E., E.E.W., M.K., J.S.V., T.L., P.V., K.B., H.B., D.O.M.-K., F.R., A.G.U., C.Pi., O.P., N.J.W., H.H., V.W.J., S.F.G., A.A.V., D.A.L., G.D.S., K.K.O., J.F.F., N.J.T., J.R.P., M.I.M. Functional follow-up experiment: L.A.D., S.M.M., R.M.R., E.D., B.R.W. Individual study design and principal investigators: J.P.B., I.N., M.A., F.D.M., W.L.L.Jr, A.T., M.Stu., V.Li., T.A.L., C.M.v.D., W.K., A.K., T.I.S., H.N., K.Pah., O.T.R., G.V.D., Y.-Y.T., S.-M.S., M.Me., H.C., J.F.W., M.V., E.J.d.G., D.I.B., H.N.K., J.-C.H., T.H., A.T.H., L.J.B., J.P.N., C.E.P., J.H., L.S.A., J.B.B., K.L.M., J.G.E., E.E.W., M.K., J.S.V., T.L., P.V., K.B., H.B., D.O.M-K., A.H., F.R., A.G.U., C.Pi., O.P., C.Po., E.H., N.J.W., H.H., V.W.J., M.-R.J., S.F.G., A.A.V., T.M.F., A.P.M., K.K.O., N.J.T., J.R.P., M.I.M., R.M.F.

Competing interests

K.Z. has a scientific collaboration with Bayer HealthCare Ltd. and Population Diagnostics Inc.

Corresponding authors

Correspondence to Mark I. McCarthy or Rachel M. Freathy.

Summary statistics from the meta-analyses are available at http://egg-consortium.org/.

Reviewer Information Nature thanks J. Whitfield and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Tables 1-16 and 18-19 (see separate excel file for Supplementary Table 17), Supplementary Figures 1-2, details of grants and funding supports and a list of acknowledgements. This file was updated on 03 October 2016 to include the consortium membership lists.

  2. 2.

    Supplementary Data

    This file contains 60 regional plots for birth weight association.

Excel files

  1. 1.

    Supplementary Table 17

    This file shows the association of BW signals with various adult metabolic and anthropometric traits. (GWAS look-ups).

About this article

Publication history

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DOI

https://doi.org/10.1038/nature19806

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