PT - JOURNAL ARTICLE AU - N. Maneka G. De Silva AU - Sylvain Sebert AU - Alexessander Couto Alves AU - Ulla Sovio AU - Shikta Das AU - Rob Taal AU - Nicole M. Warrington AU - Alexandra M. Lewin AU - Marika Kaakinen AU - Diana Cousminer AU - Elisabeth Thiering AU - Nicholas J. Timpson AU - Ville Karhunen AU - Tom Bond AU - Xavier Estivill AU - Virpi Lindi AU - Jonathan P. Bradfield AU - Frank Geller AU - Lachlan J.M. Coin AU - Marie Loh AU - Sheila J. Barton AU - Lawrence J. Beilin AU - Hans Bisgaard AU - Klaus Bønnelykke AU - Rohia Alili AU - Ida J. Hatoum AU - Katharina Schramm AU - Rufus Cartwright AU - Marie-Aline Charles AU - Vincenzo Salerno AU - Karine Clément AU - Cornelia M. van Duijn AU - Elena Moltchanova AU - Johan G. Eriksson AU - Cathy Elks AU - Bjarke Feenstra AU - Claudia Flexeder AU - Stephen Franks AU - Timothy M. Frayling AU - Rachel M. Freathy AU - Paul Elliott AU - Elisabeth Widén AU - Hakon Hakonarson AU - Andrew T. Hattersley AU - Alina Rodriguez AU - Marco Banterle AU - Joachim Heinrich AU - Barbara Heude AU - John W. Holloway AU - Albert Hofman AU - Elina Hyppönen AU - Hazel Inskip AU - Lee M. Kaplan AU - Asa K. Hedman AU - Esa Läärä AU - Holger Prokisch AU - Harald Grallert AU - Timo A. Lakka AU - Debbie A. Lawlor AU - Mads Melbye AU - Tarunveer S. Ahluwalia AU - Marcella Marinelli AU - Iona Y. Millwood AU - Lyle J. Palmer AU - Craig E. Pennell AU - John R. Perry AU - Susan M. Ring AU - Markku Savolainen AU - Kari Stefansson AU - Gudmar Thorleifsson AU - Fernando Rivadeneira AU - Marie Standl AU - Jordi Sunyer AU - Carla M.T. Tiesler AU - Andre G. Uitterlinden AU - Inga Prokopenko AU - Karl-Heinz Herzig AU - George Davey Smith AU - Paul O'Reilly AU - Janine F. Felix AU - Jessica L. Buxton AU - Alexandra I.F. Blakemore AU - Ken K. Ong AU - Struan F.A. Grant AU - Vincent W.V. Jaddoe AU - Mark I. McCarthy AU - Marjo-Riitta Järvelin ED - , TI - Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity AID - 10.1101/150516 DP - 2017 Jan 01 TA - bioRxiv PG - 150516 4099 - http://biorxiv.org/content/early/2017/06/16/150516.short 4100 - http://biorxiv.org/content/early/2017/06/16/150516.full AB - 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.