Journal article
Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
Human molecular genetics, Vol.22(13), pp.2735-2747
07/01/2013
DOI: 10.1093/hmg/ddt104
PMCID: PMC3674797
PMID: 23449627
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 × 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.
Details
- Title: Subtitle
- Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity
- Creators
- Diana L Cousminer - ,Diane J Berry - UCL Institute of Child HealthNicholas J Timpson - ,Wei Ang - The University of Western AustraliaElisabeth Thiering - Helmholtz Zentrum München— German Research Center for Environmental HealthEnda M Byrne - Queensland Institute of Medical ResearchH. Rob Taal - Erasmus Medical CenterVille Huikari - ,Jonathan P Bradfield - ,Marjan Kerkhof - ,Maria M Groen-Blokhuis - VU UniversityEskil Kreiner-Møller - University of Copenhagen, Copenhagen University HospitalMarcella Marinelli - Center for Research in Environmental Epidemiology (CREAL)Claus Holst - Copenhagen University HospitalJaakko T Leinonen - ,John R.B Perry - University of ExeterIda Surakka - ,Olli Pietiläinen - Wellcome Trust Genome CampusJohannes Kettunen - ,Verneri Anttila - Wellcome Trust Genome CampusMarika Kaakinen - University of OuluUlla Sovio - London School of Hygiene and Tropical MedicineAnneli Pouta - University of OuluShikta Das - ,Vasiliki Lagou - ,Chris Power - UCL Institute of Child HealthInga Prokopenko - ,David M Evans - ,John P Kemp - University of BristolBeate St Pourcain - University of BristolSusan Ring - University of BristolAarno Palotie - Wellcome Trust Genome CampusEero Kajantie - ,Clive Osmond - University of SouthamptonTerho Lehtimäki - University Hospital and University of TampereJorma S Viikari - ,Mika Kähönen - ,Nicole M Warrington - The University of Western AustraliaStephen J Lye - Mount Sinai HospitalLyle J Palmer - Mount Sinai HospitalCarla M.T Tiesler - Helmholtz Zentrum München— German Research Center for Environmental HealthClaudia Flexeder - Helmholtz Zentrum München— German Research Center for Environmental HealthGrant W Montgomery - Queensland Institute of Medical ResearchSarah E Medland - Queensland Institute of Medical ResearchAlbert Hofman - ,Hakon Hakonarson - The Children's Hospital of PhiladelphiaMònica Guxens - Center for Research in Environmental Epidemiology (CREAL)Meike Bartels - VU UniversityVeikko Salomaa - ,Joanne M Murabito - Boston University School of MedicineJaakko Kaprio - National Institute for Health and WelfareThorkild I.A Sørensen - Copenhagen University HospitalFerran Ballester - CIBER Epidemiologia y Salud Pública (CIBERESP)Hans Bisgaard - University of Copenhagen, Copenhagen University HospitalDorret I Boomsma - VU UniversityGerard H Koppelman - GRIAC Research Institute, Beatrix Children's Hospital, University of Groningen, University Medical Center GroningenStruan F.A Grant - The Children's Hospital of PhiladelphiaVincent W.V Jaddoe - Erasmus Medical CenterNicholas G Martin - Queensland Institute of Medical ResearchJoachim Heinrich - Helmholtz Zentrum München— German Research Center for Environmental HealthCraig E Pennell - The University of Western AustraliaOlli T Raitakari - ,Johan G Eriksson - University of HelsinkiGeorge Davey Smith - ,Elina Hyppönen - UCL Institute of Child HealthMarjo-Riitta Järvelin - University of OuluMark I McCarthy - Churchill HospitalSamuli Ripatti - Wellcome Trust Genome CampusElisabeth Widén - ,Early Growth Genetics (EGG) Consortium
- Contributors
- Jeffrey C Murray (Contributor) - University of Iowa, Dental Research
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.22(13), pp.2735-2747
- DOI
- 10.1093/hmg/ddt104
- PMID
- 23449627
- PMCID
- PMC3674797
- NLM abbreviation
- Hum Mol Genet
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 07/01/2013
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025345402771
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