Author:
De Silva N. Maneka G.,Sebert Sylvain,Alves Alexessander Couto,Sovio Ulla,Das Shikta,Taal Rob,Warrington Nicole M.,Lewin Alexandra M.,Kaakinen Marika,Cousminer Diana,Thiering Elisabeth,Timpson Nicholas J.,Karhunen Ville,Bond Tom,Estivill Xavier,Lindi Virpi,Bradfield Jonathan P.,Geller Frank,Coin Lachlan J.M.,Loh Marie,Barton Sheila J.,Beilin Lawrence J.,Bisgaard Hans,Bønnelykke Klaus,Alili Rohia,Hatoum Ida J.,Schramm Katharina,Cartwright Rufus,Charles Marie-Aline,Salerno Vincenzo,Clément Karine,van Duijn Cornelia M.,Moltchanova Elena,Eriksson Johan G.,Elks Cathy,Feenstra Bjarke,Flexeder Claudia,Franks Stephen,Frayling Timothy M.,Freathy Rachel M.,Elliott Paul,Widén Elisabeth,Hakonarson Hakon,Hattersley Andrew T.,Rodriguez Alina,Banterle Marco,Heinrich Joachim,Heude Barbara,Holloway John W.,Hofman Albert,Hyppönen Elina,Inskip Hazel,Kaplan Lee M.,Hedman Asa K.,Läärä Esa,Prokisch Holger,Grallert Harald,Lakka Timo A.,Lawlor Debbie A.,Melbye Mads,Ahluwalia Tarunveer S.,Marinelli Marcella,Millwood Iona Y.,Palmer Lyle J.,Pennell Craig E.,Perry John R.,Ring Susan M.,Savolainen Markku,Stefansson Kari,Thorleifsson Gudmar,Rivadeneira Fernando,Standl Marie,Sunyer Jordi,Tiesler Carla M.T.,Uitterlinden Andre G.,Prokopenko Inga,Herzig Karl-Heinz,Smith George Davey,O'Reilly Paul,Felix Janine F.,Buxton Jessica L.,Blakemore Alexandra I.F.,Ong Ken K.,Grant Struan F.A.,Jaddoe Vincent W.V.,McCarthy Mark I.,Järvelin Marjo-Riitta
Abstract
AbstractEarly 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.
Publisher
Cold Spring Harbor Laboratory