RT Journal Article SR Electronic T1 Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity JF bioRxiv FD Cold Spring Harbor Laboratory SP 150516 DO 10.1101/150516 A1 N. Maneka G. De Silva A1 Sylvain Sebert A1 Alexessander Couto Alves A1 Ulla Sovio A1 Shikta Das A1 Rob Taal A1 Nicole M. Warrington A1 Alexandra M. Lewin A1 Marika Kaakinen A1 Diana Cousminer A1 Elisabeth Thiering A1 Nicholas J. Timpson A1 Ville Karhunen A1 Tom Bond A1 Xavier Estivill A1 Virpi Lindi A1 Jonathan P. Bradfield A1 Frank Geller A1 Lachlan J.M. Coin A1 Marie Loh A1 Sheila J. Barton A1 Lawrence J. Beilin A1 Hans Bisgaard A1 Klaus Bønnelykke A1 Rohia Alili A1 Ida J. Hatoum A1 Katharina Schramm A1 Rufus Cartwright A1 Marie-Aline Charles A1 Vincenzo Salerno A1 Karine Clément A1 Cornelia M. van Duijn A1 Elena Moltchanova A1 Johan G. Eriksson A1 Cathy Elks A1 Bjarke Feenstra A1 Claudia Flexeder A1 Stephen Franks A1 Timothy M. Frayling A1 Rachel M. Freathy A1 Paul Elliott A1 Elisabeth Widén A1 Hakon Hakonarson A1 Andrew T. Hattersley A1 Alina Rodriguez A1 Marco Banterle A1 Joachim Heinrich A1 Barbara Heude A1 John W. Holloway A1 Albert Hofman A1 Elina Hyppönen A1 Hazel Inskip A1 Lee M. Kaplan A1 Asa K. Hedman A1 Esa Läärä A1 Holger Prokisch A1 Harald Grallert A1 Timo A. Lakka A1 Debbie A. Lawlor A1 Mads Melbye A1 Tarunveer S. Ahluwalia A1 Marcella Marinelli A1 Iona Y. Millwood A1 Lyle J. Palmer A1 Craig E. Pennell A1 John R. Perry A1 Susan M. Ring A1 Markku Savolainen A1 Kari Stefansson A1 Gudmar Thorleifsson A1 Fernando Rivadeneira A1 Marie Standl A1 Jordi Sunyer A1 Carla M.T. Tiesler A1 Andre G. Uitterlinden A1 Inga Prokopenko A1 Karl-Heinz Herzig A1 George Davey Smith A1 Paul O'Reilly A1 Janine F. Felix A1 Jessica L. Buxton A1 Alexandra I.F. Blakemore A1 Ken K. Ong A1 Struan F.A. Grant A1 Vincent W.V. Jaddoe A1 Mark I. McCarthy A1 Marjo-Riitta Järvelin A1 for the Early Growth Genetics (EGG) Consortium YR 2017 UL http://biorxiv.org/content/early/2017/06/16/150516.abstract 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.