GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.

Autor:	Couto Alves A; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK., De Silva NMG; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK., Karhunen V; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK., Sovio U; Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK.; NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Das S; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK., Taal HR; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Paediatrics, Erasmus MC, Sophia Children's Hospital, Rotterdam, Netherlands., Warrington NM; Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.; The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia., Lewin AM; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK., Kaakinen M; Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.; Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK.; Department of Clinical and Experimental Medicine, School of Biosciences and Medicine, University of Surrey, Surrey, UK., Cousminer DL; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland.; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Thiering E; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany.; Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children's Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Timpson NJ; MRC Integrative Epidemiology Unit at the University of Bristol and NIHR Bristol Biomedical Research Center, Bristol, UK.; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK., Bond TA; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK., Lowry E; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland., Brown CD; Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Estivill X; Genomics and Disease Group, Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain.; Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain.; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain., Lindi V; Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland., Bradfield JP; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Geller F; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark., Speed D; Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark.; UCL Genetics Institute, University College London, London, UK., Coin LJM; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Loh M; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (ASTAR) Singapore, Singapore., Barton SJ; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK., Beilin LJ; Medical School, Royal Perth Hospital, University of Western Australia, Perth, Western Australia, Australia., Bisgaard H; COPSAC, The Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Bønnelykke K; COPSAC, The Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Alili R; CRNH Ile de France, Hôpital Pitié-Salpêtrière, Paris, France., Hatoum IJ; CRNH Ile de France, Hôpital Pitié-Salpêtrière, Paris, France.; Obesity, Metabolism, and Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Schramm K; Institute of Human Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Human Genetics, Technische Universität München, München, Germany., Cartwright R; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Institute for Reproductive and Developmental Biology, Imperial College London, London, UK., Charles MA; Inserm, UMR 1153 (CRESS), Paris Descartes University, Villejuif, Paris, France., Salerno V; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK., Clément K; CRNH Ile de France, Hôpital Pitié-Salpêtrière, Paris, France.; Inserm, UMR 1153 (CRESS), Paris Descartes University, Villejuif, Paris, France., Claringbould AAJ; University Medical Centre Groningen, Department of Genetics, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands., van Duijn CM; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Moltchanova E; Department of Mathematics and Statistics, University of Canterbury, Christchurch, New Zealand., Eriksson JG; Department of General Practice and Primary Health Care, University of Helsinki, and Helsinki University Hospital, Helsinki, Finland.; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.; Folkhalsan Research Center, Helsinki, Finland., Elks C; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK., Feenstra B; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark., Flexeder C; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany., Franks S; Institute for Reproductive and Developmental Biology, Imperial College London, London, UK., Frayling TM; Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK., Freathy RM; Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK., Elliott P; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; National Institute for Health Research, Imperial College Biomedical Research Centre, London, UK.; Health Data Research UK London, Imperial College London, London, UK., Widén E; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland., Hakonarson H; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Hattersley AT; Institute of Biomedical and Clinical Science, University of Exeter Medical School, University of Exeter, Royal Devon and Exeter Hospital, Exeter, UK., Rodriguez A; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; School of Psychology, College of Social Science, University of Lincoln Brayford Pool Lincoln, Lincolnshire, UK., Banterle M; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK., Heinrich J; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany., Heude B; Inserm, UMR 1153 (CRESS), Paris Descartes University, Villejuif, Paris, France., Holloway JW; Human Genetics and Medical Genomics, Faculty of Medicine, University of Southampton, Southampton, UK., Hofman A; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Hyppönen E; South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.; Great Ormond Street Hospital Institute of Child Health, University College London, London, UK.; Australian Centre for Precision Health, University of South Australia Cancer Research Institute, North Terrace, Adelaide, South Australia, Australia., Inskip H; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK., Kaplan LM; Obesity, Metabolism, and Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Hedman AK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden., Läärä E; Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland., Prokisch H; Institute of Human Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.; Institute of Human Genetics, Technische Universität München, München, Germany., Grallert H; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Lakka TA; Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland.; Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland., Lawlor DA; MRC Integrative Epidemiology Unit at the University of Bristol and NIHR Bristol Biomedical Research Center, Bristol, UK.; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK., Melbye M; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Medicine, Stanford University Medical School, Stanford, CA, USA., Ahluwalia TS; COPSAC, The Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark., Marinelli M; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain.; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.; ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain., Millwood IY; Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), University of Oxford, Old Road Campus, Oxford, UK.; Medical Research Council Population Health Research Unit (MRC PHRU) at the University of Oxford, Oxford, UK., Palmer LJ; School of Public Health and Robinson Research Institute, University of Adelaide, Adelaide, Australia., Pennell CE; Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia., Perry JR; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK., Ring SM; MRC Integrative Epidemiology Unit at the University of Bristol and NIHR Bristol Biomedical Research Center, Bristol, UK.; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.; Avon Longitudinal Study of Parents and Children, School of Social and Community Medicine, University of Bristol, Bristol, UK., Savolainen MJ; Division of Internal Medicine, and Biocenter of Oulu, Faculty of Medicine, Oulu University, Oulu, Finland., Rivadeneira F; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Standl M; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany., Sunyer J; Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain.; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.; ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain., Tiesler CMT; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany.; Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children's Hospital, Ludwig-Maximilians University Munich, Munich, Germany., Uitterlinden AG; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Schierding W; Liggins Institute, University of Auckland, Auckland, New Zealand., O'Sullivan JM; Liggins Institute, University of Auckland, Auckland, New Zealand.; A Better Start-National Science, Challenge, University of Auckland, Auckland, New Zealand., Prokopenko I; Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.; Department of Clinical and Experimental Medicine, School of Biosciences and Medicine, University of Surrey, Surrey, UK.; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, UK., Herzig KH; Biocenter Oulu, University of Oulu, Oulu, Finland.; Research Unit of Biomedicine, University Oulu, Oulu, Finland.; Medical Research Center and Oulu University Hospital, University of Oulu, Oulu, Finland.; Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland., Smith GD; MRC Integrative Epidemiology Unit at the University of Bristol and NIHR Bristol Biomedical Research Center, Bristol, UK.; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK., O'Reilly P; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK., Felix JF; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Paediatrics, Erasmus MC, Sophia Children's Hospital, Rotterdam, Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Buxton JL; School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston upon Thames, UK., Blakemore AIF; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.; Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK., Ong KK; MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK., Jaddoe VWV; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.; Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands., Grant SFA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.; Institute of Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Sebert S; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland., McCarthy MI; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, UK.; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK., Järvelin MR; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland.; Medical Research Center and Oulu University Hospital, University of Oulu, Oulu, Finland.; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, UK.; Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2019 Sep 04; Vol. 5 (9), pp. eaaw3095. Date of Electronic Publication: 2019 Sep 04 (Print Publication: 2019).
DOI:	10.1126/sciadv.aaw3095
Abstrakt:	Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies. (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu