6533b821fe1ef96bd127b810
RESEARCH PRODUCT
Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Inês BarrosoInês BarrosoPeter D. SlyPeter D. SlyJose Ramon BilbaoNicholas J. TimpsonJohan G. ErikssonJohan G. ErikssonMaria M. Groen-blokhuisSijmen A. ReijneveldDariusz GruszfeldGeorge Davey SmithChristine PowerEva ReischlMandy VogelAndrew T. HattersleyØYvind HelgelandØYvind HelgelandNiina PitkänenNiina PitkänenAkram AlyassJean-paul LanghendriesElina HyppönenElina HyppönenKathrin LandgrafLoreto Santa-marinaFrank GellerChristopher D. BrownElvira VerduciKatja PahkalaKatja PahkalaOlli T. RaitakariOlli T. RaitakariJoaquin EscribanoTorben HansenHakon HakonarsonHakon HakonarsonBarbara HeudeBridget A. KnightMaties TorrentRobin N BeaumontJudith M. VonkEstelle LowryEstelle LowryPatrick G. HoltHarold SniederCarol A. WangMark I. MccarthyMark I. MccarthyChristine Frithioff-bøjsøeChristine Frithioff-bøjsøeTanja G. M. VrijkotteNatalia Vilor-tejedorLisbeth CarstensenCatharina E. M. Van BeijsterveldtVille KarhunenVirpi LindiMarjo-riitta JärvelinMarjo-riitta JärvelinTarunveer S. AhluwaliaJordi SunyerJaakko T. LeinonenClare S. MurrayKlaus BønnelykkeThorkild I. A. SørensenThorkild I. A. SørensenAndré G. UitterlindenAndré G. UitterlindenJanine F. FelixJohn A. CurtinMika KähönenJorma ViikariJorma ViikariLeo-pekka LyytikäinenOluf PedersenCarmen IñiguezHarri NiinikoskiWieland KiessKim F. MichaelsenEvie StergiakouliAnni HeiskalaAlessandra ChesiCraig E. PennellMohammed H ZafarmandMohammed H ZafarmandPeter RzehakKook K TeoAihuali LiMarie StandlVeit GroteMomoko HorikoshiEllen A. NohrEleanor WheelerEleanor WheelerRachel M. FreathyRachel M. FreathyIryna O. FedkoGerard H. KoppelmanElisabeth WidenJens-christian HolmJens-christian HolmRaimo JoroDavid MeyreMustafa AtalayTheresia M. SchnurrCamilla Schmidt MorgenCamilla Schmidt MorgenAdnan CustovicNiels GrarupTrevor A. MoriTerho LehtimäkiChristian Theil HaveAngela SimpsonMads MelbyeMads MelbyeBjarke FeenstraLawrence J. BeilinStefan JohanssonStefan JohanssonIoanna NtallaMartine VrijheidMariona BustamanteGeorge DedoussisSylvain SebertSylvain SebertSylvain SebertJonas BacelisJonas BacelisCarolina Medina-gomezCarolina Medina-gomezElisabeth ThieringKen K. OngEleftheria ZegginiEleftheria ZegginiBerthold KoletzkoKarine ClémentBo L. ChawesMette HollenstedBabette S. ZemelBabette S. ZemelMarkus ScholzHolger KirstenAntje KörnerAlbertine J. OldehinkelBarbera D. C. Van SchaikPhilippe FroguelPhilippe FroguelVincent W. V. JaddoeDorret I. BoomsmaDorret I. BoomsmaStruan F.a. GrantLoic YengoLoic YengoJonathan P. BradfieldTenna Ruest Haarmark NielsenTenna Ruest Haarmark NielsenSuzanne VogelezangSuzanne VogelezangJakob StokholmPål R. NjølstadPål R. NjølstadPål R. NjølstadBo JacobssonBo JacobssonBo JacobssonMarc VaudelMarc VaudelPeter J. Van Der MostAndreas KühnapfelMads Vendelbo LindTimo A. LakkaSaskia SelzamRobert PlominMarie-aline CharlesJouke-jan HottengaKalliope PanoutsopoulouFernando RivadeneiraFernando RivadeneiraRebecca K. VindingHans BisgaardI. S. FarooqiJoachim HeinrichJoachim HeinrichDiana L. CousminerDiana L. CousminerRicardo Closa-monasteroloClaire MonnereauClaire Monnereausubject
MaleGenetic-variationNedd4 Ubiquitin Protein LigasesPooled AnalysisBlood Pressure0302 clinical medicineHuman geneticsMendelian RandomizationYoung adultChildhealth care economics and organizationsBody mass indexAdiposityGenetics & Heredity0303 health sciencesStatistics1184 Genetics developmental biology physiologyGenomicsadulto3. Good healthCardiovascular DiseasesChild PreschoolPhysical SciencesMenarchegenetic-variationpresión sanguíneaMonosaccharide Transport ProteinsGenetic locieducationenfermedades cardiovascularesProstate-specific AntigenGenetic correlation03 medical and health sciencesSDG 3 - Good Health and Well-beingDiabetes MellitusGeneticsHumansprostate-specific antigenStatistical MethodsMolecular BiologyEcology Evolution Behavior and Systematicschildhood0604 Genetics[SDV.GEN]Life Sciences [q-bio]/GeneticsScience & TechnologyEarly Growth Genetics ConsortiumBiology and Life SciencesComputational Biologynutritional and metabolic diseasesSingle nucleotide polymorphismsMendelian Randomization AnalysisBiological TissueDiabetes Mellitus Type 2estudio de asociación genómica completagenetic factorsmendelian randomizationanálisis de la aleatorización mendelianaproteínas de transporte de monosacáridosBody mass index030217 neurology & neurosurgeryMathematicsDemographyDevelopmental BiologyCardiovascular RiskCancer ResearchobesityPhysiologyhumanosadolescenteOverweightQH426-470Genome-wide association studiesWaist–hip ratioMathematical and Statistical TechniquesMedicine and Health Sciencesbody mass index (BMI)Genetics of diseaseGenetics (clinical)2. Zero hungeradiposityMetaanalysisPhysiological ParametersConnective Tissue/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemalemedicine.symptomAnatomypooled analysisLife Sciences & BiomedicineResearch ArticleAdultcardiovascular riskAdolescentBirth weightmenarquiaAdipose tissueBiology3121 Internal medicineResearch and Analysis MethodsmedicineoverweightGenetic Predisposition to DiseaseObesity030304 developmental biologyMenarcheWaist-Hip Ratioíndice de masa corporalBody WeightCardiometabolic Risk Factorspredisposición genética a la enfermedadHeritabilityOverweightGenome Analysisyoung-adultsGenome-wide Associationíndice cintura-caderaYoung-adultsgenome-wide associationGenome-Wide Association Studydescription
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located nearNEDD4LandSLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (R(g)ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood. Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-10-12 | PLoS genetics |