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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.
Couto Alves, Alexessander; De Silva, N Maneka G; Karhunen, Ville; Sovio, Ulla; Das, Shikta; Taal, H Rob; Warrington, Nicole M; Lewin, Alexandra M; Kaakinen, Marika; Cousminer, Diana L; Thiering, Elisabeth; Timpson, Nicholas J; Bond, Tom A; Lowry, Estelle; Brown, Christopher D; Estivill, Xavier; Lindi, Virpi; Bradfield, Jonathan P; Geller, Frank; Speed, Doug; Coin, Lachlan J M; Loh, Marie; Barton, Sheila J; Beilin, Lawrence J; Bisgaard, Hans; Bønnelykke, Klaus; Alili, Rohia; Hatoum, Ida J; Schramm, Katharina; Cartwright, Rufus; Charles, Marie-Aline; Salerno, Vincenzo; Clément, Karine; Claringbould, Annique A J; van Duijn, Cornelia M; Moltchanova, Elena; Eriksson, Johan G; Elks, Cathy; Feenstra, Bjarke; Flexeder, Claudia; Franks, Stephen; Frayling, Timothy M; Freathy, Rachel M; Elliott, Paul; Widén, Elisabeth; Hakonarson, Hakon; Hattersley, Andrew T; Rodriguez, Alina; Banterle, Marco; Heinrich, Joachim.
Afiliación
  • Couto Alves A; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • De Silva NMG; School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, 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 Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Das S; Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK.
  • Taal HR; NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
  • Warrington NM; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Lewin AM; MRC Unit for Lifelong Health and Ageing at UCL, University College London, London, UK.
  • Kaakinen M; The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
  • Cousminer DL; Department of Paediatrics, Erasmus MC, Sophia Children's Hospital, Rotterdam, Netherlands.
  • Thiering E; Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.
  • Timpson NJ; The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Queensland, Australia.
  • 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; Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
  • Brown CD; Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
  • Estivill X; Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Department of Medicine, Imperial College London, Hammersmith Hospital, London, UK.
  • Lindi V; Department of Clinical and Experimental Medicine, School of Biosciences and Medicine, University of Surrey, Surrey, UK.
  • Bradfield JP; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Geller F; Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland.
  • Speed D; Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Coin LJM; Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich Neuherberg, Germany.
  • Loh M; Division of Metabolic Diseases and Nutritional Medicine, Dr von Hauner Children's Hospital, Ludwig-Maximilians University Munich, Munich, Germany.
  • Barton SJ; MRC Integrative Epidemiology Unit at the University of Bristol and NIHR Bristol Biomedical Research Center, Bristol, UK.
  • Beilin LJ; Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK.
  • Bisgaard H; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Bønnelykke K; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
  • Alili R; Department of Genetics and Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Hatoum IJ; Genomics and Disease Group, Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain.
  • Schramm K; Pompeu Fabra University (UPF), Barcelona, Catalonia, Spain.
  • Cartwright R; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Catalonia, Spain.
  • Charles MA; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Madrid, Spain.
  • Salerno V; Institute of Biomedicine, Department of Physiology, University of Eastern Finland, Kuopio, Finland.
  • Clément K; Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Claringbould AAJ; Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
  • van Duijn CM; UCL Genetics Institute, University College London, London, UK.
  • Moltchanova E; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Eriksson JG; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Elks C; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
  • Feenstra B; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
  • Flexeder C; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (ASTAR) Singapore, Singapore.
  • Franks S; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
  • Frayling TM; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  • Freathy RM; Medical School, Royal Perth Hospital, University of Western Australia, Perth, Western Australia, Australia.
  • Elliott P; COPSAC, The Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Widén E; COPSAC, The Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Hakonarson H; CRNH Ile de France, Hôpital Pitié-Salpêtrière, Paris, France.
  • Hattersley AT; CRNH Ile de France, Hôpital Pitié-Salpêtrière, Paris, France.
  • Rodriguez A; Obesity, Metabolism, and Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Banterle M; Department of Medicine, Harvard Medical School, Boston, MA, USA.
  • Heinrich J; Institute of Human Genetics, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Sci Adv ; 5(9): eaaw3095, 2019 09.
Article en En | MEDLINE | ID: mdl-31840077
ABSTRACT
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Índice de Masa Corporal / Carácter Cuantitativo Heredable / Sitios de Carácter Cuantitativo / Estudio de Asociación del Genoma Completo / Estudios de Asociación Genética Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Child / Female / Humans / Infant / Male Idioma: En Año: 2019 Tipo del documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Índice de Masa Corporal / Carácter Cuantitativo Heredable / Sitios de Carácter Cuantitativo / Estudio de Asociación del Genoma Completo / Estudios de Asociación Genética Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Límite: Adult / Child / Female / Humans / Infant / Male Idioma: En Año: 2019 Tipo del documento: Article