@article {De Silva150516, author = {N. Maneka G. De Silva and Sylvain Sebert and Alexessander Couto Alves and Ulla Sovio and Shikta Das and Rob Taal and Nicole M. Warrington and Alexandra M. Lewin and Marika Kaakinen and Diana Cousminer and Elisabeth Thiering and Nicholas J. Timpson and Ville Karhunen and Tom Bond and Xavier Estivill and Virpi Lindi and Jonathan P. Bradfield and Frank Geller and Lachlan J.M. Coin and Marie Loh and Sheila J. Barton and Lawrence J. Beilin and Hans Bisgaard and Klaus B{\o}nnelykke and Rohia Alili and Ida J. Hatoum and Katharina Schramm and Rufus Cartwright and Marie-Aline Charles and Vincenzo Salerno and Karine Cl{\'e}ment and Cornelia M. van Duijn and Elena Moltchanova and Johan G. Eriksson and Cathy Elks and Bjarke Feenstra and Claudia Flexeder and Stephen Franks and Timothy M. Frayling and Rachel M. Freathy and Paul Elliott and Elisabeth Wid{\'e}n and Hakon Hakonarson and Andrew T. Hattersley and Alina Rodriguez and Marco Banterle and Joachim Heinrich and Barbara Heude and John W. Holloway and Albert Hofman and Elina Hypp{\"o}nen and Hazel Inskip and Lee M. Kaplan and Asa K. Hedman and Esa L{\"a}{\"a}r{\"a} and Holger Prokisch and Harald Grallert and Timo A. Lakka and Debbie A. Lawlor and Mads Melbye and Tarunveer S. Ahluwalia and Marcella Marinelli and Iona Y. Millwood and Lyle J. Palmer and Craig E. Pennell and John R. Perry and Susan M. Ring and Markku Savolainen and Kari Stefansson and Gudmar Thorleifsson and Fernando Rivadeneira and Marie Standl and Jordi Sunyer and Carla M.T. Tiesler and Andre G. Uitterlinden and Inga Prokopenko and Karl-Heinz Herzig and George Davey Smith and Paul O{\textquoteright}Reilly and Janine F. Felix and Jessica L. Buxton and Alexandra I.F. Blakemore and Ken K. Ong and Struan F.A. Grant and Vincent W.V. Jaddoe and Mark I. McCarthy and Marjo-Riitta J{\"a}rvelin}, editor = {,}, title = {Genetic architecture of early childhood growth phenotypes gives insights into their link with later obesity}, elocation-id = {150516}, year = {2017}, doi = {10.1101/150516}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2017/06/16/150516}, eprint = {https://www.biorxiv.org/content/early/2017/06/16/150516.full.pdf}, journal = {bioRxiv} }