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

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DOI

  • Alexessander Couto Alves, Imperial College London, London, UK., University of Surrey, UK
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  • N. Maneka G. De Silva, Imperial College London, London, UK.
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  • Ville Karhunen, Imperial College London, London, UK.
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  • Ulla Sovio, University of Cambridge, NIHR Cambridge Biomedical Research Centre
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  • Shikta Das, Imperial College London, London, UK., UCL
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  • H. Rob Taal, Erasmus University Medical Center, Erasmus University Rotterdam
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  • Nicole M. Warrington, University of Western Australia, University of Queensland
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  • Alexandra M. Lewin, Imperial College London, London, UK., London School of Hygiene and Tropical Medicine
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  • Marika Kaakinen, Imperial College London, University of Surrey, UK
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  • Diana L. Cousminer, University of Pennsylvania, University of Eastern Finland, Helsingin yliopisto
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  • Elisabeth Thiering, Helmholtz Zentrum München - German Research Center for Environmental Health, Klinikum Grosshaden
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  • Nicholas J. Timpson, Bristol University, University of Bristol, Faculty of Medicine and Dentistry
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  • Tom A. Bond, Imperial College London, London, UK.
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  • Estelle Lowry, University of Oulu
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  • Christopher D. Brown, University of Pennsylvania
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  • Xavier Estivill, Barcelona Institute of Science and Technology, Universitat Pompeu Fabra, Barcelona, Pompeu Fabra University, Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Sidra Medical and Research Center
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  • Virpi Lindi, University of Eastern Finland
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  • Jonathan P. Bradfield, University of Pennsylvania
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  • Frank Geller, Statens Serum Institut
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  • Doug Speed
  • Lachlan J.M. Coin, Imperial College London, London, UK., University of Queensland
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  • Marie Loh, Imperial College London, London, UK., University of Oulu, Agency for Science, Technology and Research
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  • Sheila J. Barton, Medical Research Council, University of Southampton
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  • Lawrence J. Beilin, University of Western Australia
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  • Hans Bisgaard, University of Copenhagen
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  • Klaus Bønnelykke, University of Copenhagen
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  • Rohia Alili, Sorbonne Université
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  • Ida J. Hatoum, Sorbonne Université, Massachusetts General Hospital, Boston, Harvard Medical School
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  • Katharina Schramm, Helmholtz Zentrum München - German Research Center for Environmental Health, Technical University of Munich
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  • Rufus Cartwright, Imperial College London, London, UK.
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  • Marie Aline Charles, Universite Paris 5
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  • Vincenzo Salerno, Imperial College London, London, UK.
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  • Karine Clément, Sorbonne Université, Universite Paris 5
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  • Annique A.J. Claringbould, University of Groningen
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  • BIOS Consortium
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  • Cornelia M. Van Duijn, Erasmus University Medical Center
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  • Elena Moltchanova, University of Canterbury
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  • Johan G. Eriksson, Helsingin yliopisto, The National Institute for Health and Welfare, Samfundet Folkhälsan
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  • Cathy Elks, University of Cambridge, School of Clinical Medicine.
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  • Bjarke Feenstra, Statens Serum Institut
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  • Claudia Flexeder, Helmholtz Zentrum München - German Research Center for Environmental Health
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  • Stephen Franks, Imperial College London, London, UK.
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  • Timothy M. Frayling, University of Exeter Medical School
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  • Rachel M. Freathy, University of Exeter Medical School
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  • Paul Elliott, Imperial College London, London, UK.
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  • Elisabeth Widén, Helsingin yliopisto
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  • Hakon Hakonarson, University of Pennsylvania
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  • Andrew T. Hattersley, University of Exeter Medical School
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  • Alina Rodriguez, Imperial College London, London, UK., Lincoln University
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  • Marco Banterle, London School of Hygiene and Tropical Medicine
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  • Joachim Heinrich, Helmholtz Zentrum München - German Research Center for Environmental Health
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  • Early Growth Genetics (EGG) Consortium

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.

Original languageEnglish
Article numbereaaw3095
JournalScience Advances
Volume5
Issue9
Number of pages18
ISSN2375-2548
DOIs
Publication statusPublished - 2019

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