TY - JOUR T1 - Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity JF - bioRxiv DO - 10.1101/150516 SP - 150516 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 A2 - , Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/16/150516.abstract N2 - 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. ER -