GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Couto Alves, Alexessander, De Silva, N. Maneka G., Karhunen, Ville, Sovio, Ulla, Das, Shikta, Taal, H. Rob, Warrington, Nicole M., Lewin, Alexandra M., Kaakinen, Marika, Cousminer, Diana L., Thiering, Elisabeth, Timpson, Nicholas J., Bond, Tom A., Lowry, Estelle, Brown, Christopher D., Estivill, Xavier, Lindi, Virpi, Bradfield, Jonathan P., Geller, Frank, Speed, Doug, Coin, Lachlan J. M., Loh, Marie, Barton, Sheila J., Beilin, Lawrence J., Bisgaard, Hans, Bonnelykke, Klaus, Alili, Rohia, Hatoum, Ida J., Schramm, Katharina, Cartwright, Rufus, Charles, Marie-Aline, Salerno, Vincenzo, Clement, Karine, Claringbould, Annique A. J., 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, Widen, Elisabeth, Hakonarson, Hakon, Hattersley, Andrew T., Rodriguez, Alina, Banterle, Marco, Heinrich, Joachim, Heude, Barbara, Holloway, John W., Hofman, Albert, Hypponen, Elina, Inskip, Hazel, Kaplan, Lee M., Hedman, Asa K., Laara, 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 J., Rivadeneira, Fernando, Standl, Marie, Sunyer, Jordi, Tiesler, Carla M. T., Uitterlinden, Andre G., Schierding, William, O'Sullivan, Justin M., Prokopenko, Inga, Herzig, Karl-Heinz, Smith, George Davey, O'Reilly, Paul, Felix, Janine F., Buxton, Jessica L., Blakemore, Alexandra I. F., Ong, Ken K., Jaddoe, Vincent W. V., Grant, Struan F. A., Sebert, Sylvain, McCarthy, Mark I. and Jarvelin, Marjo-Riitta (2019) GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. Science Advances, 5(9), eaaw3095. ISSN (online) 2375-2548

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Early 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.

Item Type: Article
Additional Information: This work was supported by: UK Medical Research Council and Wellcome Trust (grant reference 102215/2/13/2); NIH grant R01 HD056465; Danish National Research Foundation; NIH Genes, Environment and Health Initiative (GEI; U01HG004423); NIH GEI (U01HG004438); Lundbeck Foundation (R19-A2059); Danish Medical Research Council (09-065592); French Ministry of Research; INSERM; South West NHS Research and Development; Exeter NHS Research and Development; Netherlands Organization for Health Research and Development (VIDI 016. 136. 361); European Union’s Horizon 2020 research and innovation programme under grant agreement nos. 633595 (DynaHEALTH), 733206 (LIFECYCLE), and 721567 (CAPICE); European Research Council (ERC consolidator grant, ERC-2014-CoG-648916); Academy of Finland (project grants 209072 and 129255); British Heart Foundation and Academy of Finland (grants 134839 and 129287); National Public Health Institute, Helsinki, Finland; World Cancer Research Fund (WCRF UK) and World Cancer Research Fund International (2017/1641); Wellcome Trust (WT205915); European Commission under the Marie Curie Intra-European Fellowship (project MARVEL, PIEF-GA-2013-626461); Instituto de Salud Carlos III (CB06/02/0041, FIS PI041436, PI081151, PI041705, and PS09/00432 and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/02647); Spanish Ministry of Science and Innovation (SAF2008-00357); European Commission (ENGAGE project and grant agreement HEALTH-F4-2007-201413); Fundació La Marató de TV3; Generalitat de Catalunya-CIRIT 1999SGR 00241; Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296); National Health and Medical Research Council of Australia (grant IDs 403981 and 003209); Canadian Institutes of Health Research (grant ID MOP-82893); Royal Society of New Zealand Marsden Fund (grant 16-UOO-072); Academy of Finland (project grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics, and SALVE); University Hospital Oulu; Biocenter; University of Oulu, Finland (75617); European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643); NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01); NIH/NIMH (5R01MH63706:02); Medical Research Council, United Kingdom (G0500539 and G0600705, PrevMetSyn/SALVE, MR/M013138, G0802782); Wellcome Trust (project grant GR069224); and EU Framework Programme 7 EurHEALTHAgeing 277849.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing > School of Life Sciences, Pharmacy and Chemistry
Faculty of Science, Engineering and Computing
Depositing User: Jessica Buxton
Date Deposited: 20 Sep 2019 14:44
Last Modified: 20 Sep 2019 14:44

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