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Get Free AccessEarly childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Alexessander Couto Alves, N. Maneka G. De Silva, Ville Karhunen, Ulla Sovio, Shikta Das, H. Rob Taal, Nicole M. Warrington, Alex Lewin, Marika Kaakinen, Diana L. Cousminer, Elisabeth Thiering, Nicholas J. Timpson, Tom A. Bond, Estelle Lowry, Christopher D. Brown, Xavier Estivill, Virpi Lindi, Jonathan P. Bradfield, Frank Geller, Doug Speed, Lachlan Coin, Marie Loh, Sheila J. Barton, Lawrence J. Beilin, Hans Bisgaard, Klaus Bønnelykke, Rohia Alili, Ida J. Hatoum, Katharina Schramm, Rufus Cartwright, Marie‐Aline Charles, Vincenzo Salerno, Karine Clément, Annique Claringbould, Cornelia M. van Duijn, Elena Moltchanova, Johan G. Eriksson, Cathy E. Elks, Bjarke Feenstra, Claudia Flexeder, Paul W. Franks, Timothy M. Frayling, Rachel M. Freathy, Paul Elliott, Elisabeth Widén, Hákon Hákonarson, Andrew T. Hattersley, Alina Rodriguez, Marco Banterle, Joachim Heinrich, Barbara Heude, John W. Holloway, Albert Hofman, Elina Hyppönen, Hazel Inskip, Lee M. Kaplan, Åsa K. Hedman, Esa Läärä, Holger Prokisch, Harald Grallert, Timo A. Lakka, Debbie A. Lawlor, Mads Melbye, Tarunveer S. Ahluwalia, M. Marinelli, Iona Y. Millwood, Lyle J. Palmer, Craig E. Pennell, John R. B. Perry, Susan M. Ring, Markku J. Savolainen, Fernando Rivadeneira, Marie Standl, Jordi Sunyer, Carla M. T. Tiesler, André G. Uitterlinden, William Schierding, Justin M. O’Sullivan, Inga Prokopenko, Karl‐Heinz Herzig, George Davey Smith, Paul F. O’Reilly, Janine F. Felix, Jessica L. Buxton, Alexandra I. F. Blakemore, Ken K. Ong, Vincent W. V. Jaddoe, Struan F.A. Grant, Sylvain Sebért, Mark I. McCarthy, Paul M Ridker (2019). GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. , 5(9), DOI: https://doi.org/10.1126/sciadv.aaw3095.
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Type
Article
Year
2019
Authors
91
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1126/sciadv.aaw3095
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