期刊
HUMAN MOLECULAR GENETICS
卷 22, 期 13, 页码 2735-2747出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddt104
关键词
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资金
- Academy of Finland [120315, 134839, 129297, 218029, 209072, 129255, 126925, 121584, 124282, 129378, 117787, 41071, 100499, 205585, 118555, 104781, 129418, 141054]
- Academy of Finland Center of Excellence in Complex Disease Genetics [213506, 129680]
- Australian National Health and Medical Research Council [241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498]
- Australian Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016, DP0343921]
- British Heart Foundation
- Canadian Institutes of Health Research [MOP-82893]
- Conselleria de Sanitat Generalitat Valenciana
- Fundacion Roger Torne
- Dutch Asthma Fonds
- Emil Aaltonen Foundation
- Erasmus Medical Center, Rotterdam
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development [21000074, ZonMw 90700303, 916.10159]
- European Commission (ENGAGE project) [HEALTH-F4-2007-201413]
- European Commission (EURO-BLCS) [QLG1-CT-2000-01643]
- European Research Council [ERC-230374]
- Finnish Cultural Foundation
- Finnish Foundation of Cardiovascular Research
- Fundacio La Marato de TV3
- Generalitat de Catalunya [CIRIT 1999SGR 00241]
- Genomics of Developmental Trajectories in Twins [1RC2MH089 995-01]
- German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]
- Infants Research Foundation
- Institute Development Award from the Children's Hospital of Philadelphia
- Instituto de Salud Carlos III [CB06/02/0041, G03/176, FIS PI041436, PI081151, PI041705, PS09/00432, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647]
- Juho Vainio Foundation
- Ludwig-Maximilians-University's innovative research priority project MC-Health
- Medical Research Council [G0601653, G0000934, G0500539, G0600705]
- National Institutes of Health [R01 HD056465, 5R01MH63706:02]
- National Institute for Alcohol Abuse and Alcoholism [AA-12502, AA-09203, AA-08315]
- NIH Heart, Lung and Blood Institute [5R01HL087679-02]
- NIH Heart, Lung and Blood Institute through the STAMPEED program [1RL1MH083268-01]
- National Health and Medical Research Council of Australia [403981, 003209]
- Netherlands Organization for Scientific research [NWO/SPI 56-464-14192]
- Spanish Ministry of Science and Innovation [SAF2008-00357]
- Stichting Astmabestrijding and Ministry of the Environment
- Social Insurance Institution of Finland
- Telethon Institute for Child Health Research and Women
- Twin-family database for behavior genetics and genomics studies [NWO 480-04-004]
- Type 1 Diabetes Genetics Consortium [U01 DK062418]
- Paavo Nurmi Foundation
- Raine Medical Research Foundation
- Research Development Award from the Cotswold Foundation
- UK Medical Research Council [74882]
- University of Bristol
- University of Western Australia
- University Hospital Oulu
- University of Oulu [75617]
- UWA Faculty of Medicine, Dentistry and Health Sciences
- Wellcome Trust [076467, 068545/Z/02, 084762MA, 092447/Z/10/Z, WT083431MA]
- ZonMw: the Netherlands Organisation for Health Research and Development
- Helsinki Biomedical Graduate Program
- MRC Centre for Causal Analyses in Translational Epidemiology [RD1634]
- European Community's Seventh Framework Programme [FP7/2007-2013]
- European Community's ENGAGE project [HEALTH-F4-2007-201413]
- Tampere and Turku University Hospital Medical Funds [9M048, 9N035]
- Tampere Tuberculosis Foundation
- National Health and Medical Research Council [613608]
- Academy of Finland (AKA) [218029, 134839, 209072, 218029, 209072, 129418, 134839, 129418] Funding Source: Academy of Finland (AKA)
- Medical Research Council [MC_PC_15018, MC_UP_A620_1017, G0801056B, G0000934, MC_PC_U127592696, G0600705, U1475000001, MC_U127592696, MC_UU_12011/1, MC_UU_12013/3, G0601653, MC_UP_A620_1014, MC_UU_12013/4, MC_UU_12011/4, G9815508] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10082, NF-SI-0611-10099, NF-SI-0611-10219] Funding Source: researchfish
- Novo Nordisk Fonden [NNF12OC1016374] Funding Source: researchfish
- MRC [MC_U127592696, G0000934, MC_UU_12011/4, G0600705, MC_PC_U127592696, MC_UU_12013/3, MC_UU_12013/4, G0601653, MC_UP_A620_1017] Funding Source: UKRI
- Wellcome Trust [092447/Z/10/Z] Funding Source: Wellcome Trust
The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P 1.67 10(8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.
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