Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
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Abstract
A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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The record
- Venue
- Human Molecular Genetics
- Topic
- Genetic Associations and Epidemiology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Center for Advancing Translational SciencesNational Institute of Child Health and Human DevelopmentNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesNational Human Genome Research InstituteNational Institute of Mental HealthItä-Suomen YliopistoBiotechnology and Biological Sciences Research CouncilNational Heart, Lung, and Blood InstituteNational Institute for Health and Care ResearchBiocenter, University of OuluMünchner Zentrum für Gesundheitswissenschaften, Ludwig-Maximilians-Universität MünchenNIHR Imperial Biomedical Research CentreInstituto de Salud Carlos IIINational Institutes of HealthNational Institute of Neurological Disorders and StrokeGeorgia Clinical and Translational Science AllianceLung Foundation NetherlandsWellcome TrustUniversität LeipzigNederlandse Organisatie voor Wetenschappelijk OnderzoekDeutsche ForschungsgemeinschaftSvenska LäkaresällskapetSuomen KulttuurirahastoOulun YliopistoErasmus Medisch CentrumHelmholtz-Zentrum für UmweltforschungPaavo Nurmen SäätiöNovo NordiskJuho Vainion SäätiöEuropean CommissionEngineering and Physical Sciences Research CouncilGeneralitat de CatalunyaGeneralitat ValencianaErasmus Universiteit RotterdamKelaStrategiske ForskningsrådZonMwNorges ForskningsrådUniversity of OxfordKuopion Yliopistollinen SairaalaUniversity of BristolCancer Research UKAsthma and Lung UKMedical Research CouncilFundació la Marató de TV3Bundesministerium für Bildung und ForschungNational Cancer InstituteLundbeckfondenMinisterio de Ciencia e InnovaciónCanadian Institutes of Health ResearchDiabetes UKJuvenile Diabetes Research Foundation International
- Keywords
- BiologyGeneticsGenome-wide association studyBody mass indexGenetic associationGenomeGeneGenotypeSingle-nucleotide polymorphism
- Has abstract in OpenAlex
- yes