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Couto Alves, A., De Silva, N. M. G., Karhunen, V., Sovio, U., Das, S., … Taal, H. R. (2019). GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. Science Advances, 5(9), eaaw3095. https://doi.org/10.1126/sciadv.aaw3095

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

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Author: Alves, Alexessander Couto1,2; De Silva, N. Maneka G.1; Karhunen, Ville1;
Sovio, Ulla3,4; Das, Shikta1,5; Taal, H. Rob6,7; Warrington, Nicole M.8,9; Lewin, Alexandra M.1,10; Kaakinen, Marika11,12,13; Cousminer, Diana L.14,15,16; Thiering, Elisabeth17,18; Timpson, Nicholas J.19,20,21; Bond, Tom A.1; Lowry, Estelle22; Brown, Christopher D.23,24; Estivill, Xavier25,26,27,28,29; Lindi, Virpi15; Bradfield, Jonathan P.30; Geller, Frank31; Speed, Doug32,33; Coin, Lachlan J. M.1,34; Loh, Marie1,22,35; Barton, Sheila J.36,37,38; Beilin, Lawrence J.39; Bisgaard, Hans40; Bonnelykke, Klaus40; Alili, Rohia41; Hatoum, Ida J.41,42,43; Schramm, Katharina44,45; Cartwright, Rufus1,46; Charles, Marie-Aline47; Salerno, Vincenzo1; Clement, Karine41,47; Claringbould, Annique A. J.48; van Duijn, Cornelia M.49; Moltchanova, Elena50; Eriksson, Johan G.51,52,53,54; Elks, Cathy55; Feenstra, Bjarke31; Flexeder, Claudia17; Franks, Stephen46; Frayling, Timothy M.56; Freathy, Rachel M.56; Elliott, Paul1,57,58; Widen, Elisabeth16; Hakonarson, Hakon14,30,59,60; Hattersley, Andrew T.56; Rodriguez, Alina1,61; Banterle, Marco10; Heinrich, Joachim17; Heude, Barbara47; Holloway, John W.62; Hofman, Albert6,49; Hypponen, Elina63,64,65; Inskip, Hazel36,37,38; Kaplan, Lee M.42,43; Hedman, Asa K.66,67; Läärä, Esa68; Prokisch, Holger44,45; Grallert, Harald69,70; Lakka, Timo A.15,71,72; Lawlor, Debbie A.19,20,21; Melbye, Mads31,73,74; Ahluwalia, Tarunveer S.40; Marinelli, Marcella27,28,75; Millwood, Iona Y.76,77,78; Palmer, Lyle J.; Pennell, Craig E.8; Perry, John R.55; Ring, Susan M.19,20,21,79; Savolainen, Markku J.80,81; Rivadeneira, Fernando49,82; Standl, Marie17; Sunyer, Jordi26,27,28,75; Tiesler, Carla M. T.17,18; Uitterlinden, Andre G.49,82; Schierding, William83; O'Sullivan, Justin M.83,84; Prokopenko, Inga11,13,66,85; Herzig, Karl-Heinz86,87,88,89,90; Smith, George Davey19,20,21; O'Reilly, Paul1,91; Felix, Janine F.6,7,49; Buxton, Jessica L.92; Blakemore, Alexandra I. F.93,94; Ong, Ken K.55; Jaddoe, Vincent W. V.6,49; Grant, Struan F. A.14,30,59,60; Sebert, Sylvain1,22,86; McCarthy, Mark I.66,85,95,96; Jarvelin, Marjo-Riitta1,22,86,88,89,93,97
Organizations: 1Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
2Univ Surrey, Fac Hlth & Med Sci, Sch Biosci & Med, Guildford, Surrey, England.
3Univ Cambridge, Dept Obstet & Gynaecol, Cambridge, England.
4NIHR Cambridge Biomed Res Ctr, Cambridge, England.
5UCL, MRC Unit Lifelong Hlth & Ageing UCL, London, England.
6Erasmus MC, Univ Med Ctr Rotterdam, Generat R Study Grp, Rotterdam, Netherlands.
7Sophia Childrens Univ Hosp, Erasmus MC, Dept Paediat, Rotterdam, Netherlands.
8Univ Western Australia, Div Obstet & Gynaecol, Perth, WA, Australia.
9Univ Queensland, Diamantina Inst, Woolloongabba, Qld, Australia.
10London Sch Hyg & Trop Med, Dept Med Stat, London, England.
11Imperial Coll London, Hammersmith Hosp, Sch Publ Hlth, Dept Genom Common Dis, London, England.
12Imperial Coll London, Hammersmith Hosp, Dept Med, Ctr Pharmacol & Therapeut,Div Expt Med, London, England.
13Univ Surrey, Sch Biosci & Med, Dept Clin & Expt Med, Guildford, Surrey, England.
14Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.
15Univ Eastern Finland, Dept Physiol, Inst Biomed, Kuopio, Finland.
16Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
17German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Munich, Germany.
18Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Div Metab Dis & Nutrit Med, Munich, Germany.
19Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
20NIHR Bristol Biomed Res Ctr, Bristol, Avon, England.
21Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England.
22Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.
23Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
24Univ Penn, Perelman Sch Med, Inst Biomed Informat, Philadelphia, PA 19104 USA.
25Ctr Genom Regulat CRG, Bioinformat & Genom Programme, Genom & Dis Grp, Barcelona, Catalonia, Spain.
26Pompeu Fabra Univ UPF, Barcelona, Catalonia, Spain.
27Hosp del Mar Med Res Inst IMIM, Barcelona, Catalonia, Spain.
28Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Madrid, Spain.
29Sidra Med & Res Ctr, Doha, Qatar.
30Childrens Hosp Philadelphia, Abramson Res Ctr, Ctr Appl Genom, Philadelphia, PA 19104 USA.
31Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark.
32Aarhus Univ, AIAS, Aarhus, Denmark.
33UCL, UCL Genet Inst, London, England.
34Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
35ASTAR, TLGM, Singapore, Singapore.
36Univ Southampton, Southampton Gen Hosp, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
37Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England.
38Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England.
39Univ Western Australia, Royal Perth Hosp, Med Sch, Perth, WA, Australia.
40Univ Copenhagen, Fac Hlth Sci, Copenhagen Prospect Studies Asthma Childhood, COPSAC, Copenhagen, Denmark.
41Hop La Pitie Salpetriere, CRNH Ile France, Paris, France.
42Massachusetts Gen Hosp, Obes Metab & Nutr Inst & Gastrointestinal Unit, Boston, MA 02114 USA.
43Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
44German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany.
45Tech Univ Munich, Inst Human Genet, Munich, Germany.
46Imperial Coll London, Inst Reprod & Dev Biol, London, England.
47Paris Descartes Univ, INSERM, UMR 1153, CRESS, Paris, France.
48Univ Med Ctr Groningen, Dept Genet, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands.
49Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
50Univ Canterbury, Dept Math & Stat, Christchurch, New Zealand.
51Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
52Helsinki Univ Hosp, Helsinki, Finland.
53Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
54Folkhalsan Res Ctr, Helsinki, Finland.
55Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge, England.
56Univ Exeter, Med Sch, Inst Biomed & Clin Sci, Royal Devon & Exeter Hosp, Exeter, Devon, England.
57Imperial Coll, Biomed Res Ctr, Natl Inst Hlth Res, London, England.
58Imperial Coll London, Hlth Data Res UK London, London, England.
59Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
60Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
61Univ Lincoln Brayford Pool Lincoln, Coll Social Sci, Sch Psychol, Lincoln, Lincs, England.
62Univ Southampton, Fac Med, Human Genet & Med Genom, Southampton, Hants, England.
63South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
64UCL, Great Ormond St Hosp Inst Child Hlth, London, England.
65Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, North Terrace, Adelaide, SA, Australia.
66Univ Oxford, Wellcome Ctr Human Genet, Oxford, England.
67Karolinska Inst, Dept Med, Cardiovasc Med Unit, Stockholm, Sweden.
68Univ Oulu, Res Unit Math Sci, Oulu, Finland.
69German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
70German Ctr Diabet Res DZD, Neuherberg, Germany.
71Kuopio Res Inst Exercise Med, Kuopio, Finland.
72Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland.
73Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark.
74Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA.
75Ctr Res Environm Epidemiol CREAL, ISGlobal, Barcelona, Spain.
76Univ Oxford, Clin Trial Serv Unit, Old Rd Campus, Oxford, England.
77Univ Oxford, Epidemiol Studies Unit CTSU, Old Rd Campus, Oxford, England.
78Univ Oxford, MRC PHRU, Oxford, England.
79Univ Bristol, Sch Social & Community Med, Avon Longitudinal Study Parents & Children, Bristol, Avon, England.
80Oulu Univ, Fac Med, Div Internal Med, Oulu, Finland.
81Oulu Univ, Fac Med, Bioctr Oulu, Oulu, Finland.
82Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
83Univ Auckland, Liggins Inst, Auckland, New Zealand.
84Univ Auckland, A Better Start Natl Sci, Challenge, Auckland, New Zealand.
85Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
86Univ Oulu, Bioctr Oulu, Oulu, Finland.
87Univ Oulu, Res Unit Biomed, Oulu, Finland.
88Univ Oulu, Med Res Ctr, Oulu, Finland.
89Univ Oulu, Oulu Univ Hosp, Oulu, Finland.
90Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland.
91Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, Crespigny Pk, London, England.
92Univ Kingston, Sch Life Sci Pharm & Chem, Kingston Upon Thames, Surrey, England.
93Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England.
94Imperial Coll London, Div Diabet Endocrinol & Metab, Sect Investigat Med, London, England.
95Oxford Univ Hosp NHS Fdn Trust, John Radcliffe Hosp, Oxford NIHR Biomed Res Ctr, Oxford, England.
96Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
97Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2019112043229
Language: English
Published: American Association for the Advancement of Science, 2019
Publish Date: 2019-11-20
Description:

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.

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Series: Science advances
ISSN: 2375-2548
ISSN-E: 2375-2548
ISSN-L: 2375-2548
Volume: 5
Issue: 9
Article number: eaaw3095
DOI: 10.1126/sciadv.aaw3095
OADOI: https://oadoi.org/10.1126/sciadv.aaw3095
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Article
Funding: All the authors acknowledge the following sponsors for support: 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.
EU Grant Number: (633595) DYNAHEALTH - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging
(733206) LIFECYCLE - Early-life stressors and LifeCycle health
(277849) EURHEALTHAGEING - European ResearcH on DevElopmentAL, BirtH and Genetic Determinants of Ageing
Academy of Finland Grant Number: 129269
114194
Detailed Information: 129269 (Academy of Finland Funding decision)
114194 (Academy of Finland Funding decision)
Copyright information: © 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).
  https://creativecommons.org/licenses/by/4.0/