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Author Cousminer, D.L.; Berry, D.J.; Timpson, N.J.; Ang, W.; Thiering, E.; Byrne, E.M.; Taal, H.R.; Huikari, V.; Bradfield, J.P.; Kerkhof, M.; Groen-Blokhuis, M.M.; Kreiner-Moller, E.; Marinelli, M.; Holst, C.; Leinonen, J.T.; Perry, J.R.B.; Surakka, I.; Pietilainen, O.; Kettunen, J.; Anttila, V.; Kaakinen, M.; Sovio, U.; Pouta, A.; Das, S.; Lagou, V.; Power, C.; Prokopenko, I.; Evans, D.M.; Kemp, J.P.; St Pourcain, B.; Ring, S.; Palotie, A.; Kajantie, E.; Osmond, C.; Lehtimaki, T.; Viikari, J.S.; Kahonen, M.; Warrington, N.M.; Lye, S.J.; Palmer, L.J.; Tiesler, C.M.T.; Flexeder, C.; Montgomery, G.W.; Medland, S.E.; Hofman, A.; Hakonarson, H.; Guxens, M.; Bartels, M.; Salomaa, V.; Murabito, J.M.; Kaprio, J.; Sorensen, T.I.A.; Ballester, F.; Bisgaard, H.; Boomsma, D.I.; Koppelman, G.H.; Grant, S.F.A.; Jaddoe, V.W.V.; Martin, N.G.; Heinrich, J.; Pennell, C.E.; Raitakari, O.T.; Eriksson, J.G.; Smith, G.D.; Hypponen, E.; Jarvelin, M.-R.; McCarthy, M.I.; Ripatti, S.; Widen, E. url  doi
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  Title Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity Type Journal Article
  Year (down) 2013 Publication Human Molecular Genetics Abbreviated Journal Hum Mol Genet  
  Volume 22 Issue 13 Pages 2735-2747  
  Keywords Adiposity/*genetics; Adolescent; Age Factors; Body Height/*genetics; Body Mass Index; Child; Female; Follow-Up Studies; Gene Expression; Genetic Linkage; *Genome-Wide Association Study; Humans; Male; Menarche; Mitogen-Activated Protein Kinase 3/genetics/metabolism; Neoplasms/genetics/metabolism; Phenotype; Puberty/*genetics; *Quantitative Trait Loci; Signal Transduction; Transforming Growth Factor beta/metabolism; Young Adult  
  Abstract 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 x 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.  
  Address Institute for Molecular Medicine, and Department of Public Health, University of Helsinki, Helsinki, Finland  
  Corporate Author Early Growth Genetics (EGG) Consortium Thesis  
  Impact Factor 06,393 First Author Cousminer, D.L. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Widen, E.  
  ISSN 0964-6906 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23449627; PMCID:PMC3674797 Approved no  
  Call Number Serial 95  
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