Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity

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dc.contributor.authorCousminer, D.
dc.contributor.authorBerry, D.
dc.contributor.authorTimpson, N.
dc.contributor.authorAng, W.
dc.contributor.authorThiering, E.
dc.contributor.authorByrne, E.
dc.contributor.authorTaal, H.
dc.contributor.authorHuikari, V.
dc.contributor.authorBradfield, J.
dc.contributor.authorKerkhof, M.
dc.contributor.authorGroen-Blokhuis, M.
dc.contributor.authorKreiner-Møller, E.
dc.contributor.authorMarinelli, M.
dc.contributor.authorHolst, C.
dc.contributor.authorLeinonen, J.
dc.contributor.authorPerry, J.
dc.contributor.authorSurakka, I.
dc.contributor.authorKettunen, J.
dc.contributor.authorAnttila, V.
dc.contributor.authorKaakinen, M.
dc.contributor.authoret al.
dc.date.issued2013
dc.description.abstractThe 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.
dc.description.statementofresponsibilityDiana L. Cousminer ... Lyle J. Palmer ... The ReproGen Consortium ... et al. for the Early Growth Genetics (EGG) Consortium
dc.identifier.citationHuman Molecular Genetics, 2013; 22(13):2735-2747
dc.identifier.doi10.1093/hmg/ddt104
dc.identifier.issn0964-6906
dc.identifier.issn1460-2083
dc.identifier.orcidPalmer, L. [0000-0002-1628-3055]
dc.identifier.urihttp://hdl.handle.net/2440/97675
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/arc/A7960034
dc.relation.granthttp://purl.org/au-research/grants/arc/A79906588
dc.relation.granthttp://purl.org/au-research/grants/arc/A79801419
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0770096
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0212016
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0343921
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/613608
dc.rights© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com
dc.source.urihttps://doi.org/10.1093/hmg/ddt104
dc.subjectReproGen Consortium
dc.subjectEarly Growth Genetics (EGG) Consortium
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectMitogen-Activated Protein Kinase 3
dc.subjectTransforming Growth Factor beta
dc.subjectBody Mass Index
dc.subjectBody Height
dc.subjectFollow-Up Studies
dc.subjectAge Factors
dc.subjectSignal Transduction
dc.subjectGene Expression
dc.subjectPuberty
dc.subjectMenarche
dc.subjectPhenotype
dc.subjectQuantitative Trait Loci
dc.subjectAdolescent
dc.subjectChild
dc.subjectFemale
dc.subjectMale
dc.subjectAdiposity
dc.subjectGenome-Wide Association Study
dc.subjectYoung Adult
dc.subjectGenetic Linkage
dc.titleGenome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
dc.typeJournal article
pubs.publication-statusPublished

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