%0 Journal Article %A N. Maneka G. De Silva %A Sylvain Sebert %A Alexessander Couto Alves %A Ulla Sovio %A Shikta Das %A Rob Taal %A Nicole M. Warrington %A Alexandra M. Lewin %A Marika Kaakinen %A Diana Cousminer %A Elisabeth Thiering %A Nicholas J. Timpson %A Ville Karhunen %A Tom Bond %A Xavier Estivill %A Virpi Lindi %A Jonathan P. Bradfield %A Frank Geller %A Lachlan J.M. Coin %A Marie Loh %A Sheila J. Barton %A Lawrence J. Beilin %A Hans Bisgaard %A Klaus Bønnelykke %A Rohia Alili %A Ida J. Hatoum %A Katharina Schramm %A Rufus Cartwright %A Marie-Aline Charles %A Vincenzo Salerno %A Karine Clément %A Cornelia M. van Duijn %A Elena Moltchanova %A Johan G. Eriksson %A Cathy Elks %A Bjarke Feenstra %A Claudia Flexeder %A Stephen Franks %A Timothy M. Frayling %A Rachel M. Freathy %A Paul Elliott %A Elisabeth Widén %A Hakon Hakonarson %A Andrew T. Hattersley %A Alina Rodriguez %A Marco Banterle %A Joachim Heinrich %A Barbara Heude %A John W. Holloway %A Albert Hofman %A Elina Hyppönen %A Hazel Inskip %A Lee M. Kaplan %A Asa K. Hedman %A Esa Läärä %A Holger Prokisch %A Harald Grallert %A Timo A. Lakka %A Debbie A. Lawlor %A Mads Melbye %A Tarunveer S. Ahluwalia %A Marcella Marinelli %A Iona Y. Millwood %A Lyle J. Palmer %A Craig E. Pennell %A John R. Perry %A Susan M. Ring %A Markku Savolainen %A Kari Stefansson %A Gudmar Thorleifsson %A Fernando Rivadeneira %A Marie Standl %A Jordi Sunyer %A Carla M.T. Tiesler %A Andre G. Uitterlinden %A Inga Prokopenko %A Karl-Heinz Herzig %A George Davey Smith %A Paul O'Reilly %A Janine F. Felix %A Jessica L. Buxton %A Alexandra I.F. Blakemore %A Ken K. Ong %A Struan F.A. Grant %A Vincent W.V. Jaddoe %A Mark I. McCarthy %A Marjo-Riitta Järvelin %A for the Early Growth Genetics (EGG) Consortium %T Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity %D 2017 %R 10.1101/150516 %J bioRxiv %P 150516 %X Early childhood growth patterns are associated with adult metabolic health, but the underlying mechanisms are unclear. We performed genome-wide meta-analyses and follow-up in up to 22,769 European children for six early growth phenotypes derived from longitudinal data: peak height and weight velocities, age and body mass index (BMI) at adiposity peak (AP ~9 months) and rebound (AR ~5-6 years). We identified four associated loci (P< 5x10−8): LEPR/LEPROT with BMI at AP, FTO and TFAP2B with Age at AR and GNPDA2 with BMI at AR. The observed AR-associated SNPs at FTO, TFAP2B and GNPDA2 represent known adult BMI-associated variants. The common BMI at AP associated variant at LEPR/LEPROT was not associated with adult BMI but was associated with LEPROT gene expression levels, especially in subcutaneous fat (P<2x10−51). We identify strong positive genetic correlations between early growth and later adiposity traits, and analysis of the full discovery stage results for Age at AR revealed enrichment for insulin-like growth factor 1 (IGF-1) signaling and apolipoprotein pathways. This genome-wide association study suggests mechanistic links between early childhood growth and adiposity in later childhood and adulthood, highlighting these early growth phenotypes as potential targets for the prevention of obesity. %U https://www.biorxiv.org/content/biorxiv/early/2017/06/16/150516.full.pdf