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

Da Silva 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, Consortium, BIOS, van Duijin, Cornelia M., Moltchanova, Elena, Eriksson, Johan G., Elks, Cathy, Feenstra, Bjarke, Flexeder, Claudia, Franks, Stephen, Frayling, Timothy M., Freathy, Rachel M., Elliot, 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 L. F, Ong, Ken K., Jaddoe, Vincent W.V, Grant, Struan F.A, Sebert, Sylvain, McCarthy, Mark L. and Jarvelin, Marjo-Riitta (2019) GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI Science Advances, 5 (9).

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Abstract

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
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Da Silva Couto Alves, Alexessandera.coutoalves@surrey.ac.uk
De Silva, N. Maneka G.
Karhunen, Ville
Sovio, Ulla
Das, Shikta
Taal, H. Rob
Warrington, Nicole M.
Lewin, Alexandra M.
Kaakinen, Marikam.kaakinen@surrey.ac.uk
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
Consortium, BIOS
van Duijin, Cornelia M.
Moltchanova, Elena
Eriksson, Johan G.
Elks, Cathy
Feenstra, Bjarke
Flexeder, Claudia
Franks, Stephen
Frayling, Timothy M.
Freathy, Rachel M.
Elliot, 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, Ingai.prokopenko@surrey.ac.uk
Herzig, Karl-Heinz
Smith, George Davey
O'Reilly, Paul
Felix, Janine F.
Buxton, Jessica L.
Blakemore, Alexandra L. F
Ong, Ken K.
Jaddoe, Vincent W.V
Grant, Struan F.A
Sebert, Sylvain
McCarthy, Mark L.
Jarvelin, Marjo-Riitta
Date : 4 September 2019
DOI : 10.1126/sciadv.aaw3095
OA Location : https://advances.sciencemag.org/content/5/9/eaaw3095
Copyright Disclaimer : Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
Depositing User : James Marshall
Date Deposited : 16 Mar 2020 10:04
Last Modified : 16 Mar 2020 14:58
URI: http://epubs.surrey.ac.uk/id/eprint/853928

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