Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

Suzanne VogelezangJonathan P BradfieldTarunveer S AhluwaliaJohn A CurtinTimo A LakkaNiels GrarupMarkus ScholzPeter J van der MostClaire MonnereauEvie StergiakouliAnni HeiskalaMomoko HorikoshiIryna O FedkoNatalia Vilor-TejedorDiana L CousminerMarie StandlCarol A WangJorma ViikariFrank GellerCarmen ÍñiguezNiina PitkänenAlessandra ChesiJonas BacelisLoic YengoMaties TorrentIoanna NtallaØyvind HelgelandSaskia SelzamJudith M VonkMohammed H ZafarmandBarbara HeudeIsmaa Sadaf FarooqiAkram AlyassRobin N BeaumontChristian T HavePeter RzehakJose Ramon BilbaoTheresia M SchnurrInês BarrosoKlaus BønnelykkeLawrence J BeilinLisbeth CarstensenMarie-Aline CharlesBo ChawesKarine ClémentRicardo Closa-MonasteroloAdnan CustovicJohan G ErikssonJoaquin EscribanoMaria Groen-BlokhuisVeit GroteDariusz GruszfeldHakon HakonarsonTorben HansenAndrew T HattersleyMette HollenstedJouke-Jan HottengaElina HyppönenStefan JohanssonRaimo JoroMika KähönenVille KarhunenWieland KiessBridget A KnightBerthold KoletzkoAndreas KühnapfelKathrin LandgrafJean-Paul LanghendriesTerho LehtimäkiJaakko T LeinonenAihuali LiVirpi LindiEstelle LowryMariona BustamanteCarolina Medina-GomezMads MelbyeKim F MichaelsenCamilla S MorgenTrevor A MoriTenna R H NielsenHarri NiinikoskiAlbertine J OldehinkelKatja PahkalaKalliope PanoutsopoulouOluf PedersenCraig E PennellChristine PowerSijmen A ReijneveldFernando RivadeneiraAngela SimpsonPeter D SlyJakob StokholmKook K TeoElisabeth ThieringNicholas J TimpsonAndré G UitterlindenCatharina E M van BeijsterveldtBarbera D C van SchaikMarc VaudelElvira VerduciRebecca K VindingMandy VogelEleftheria ZegginiSylvain SebertMads V LindChristopher D BrownLoreto Santa-MarinaEva ReischlChristine Frithioff-BøjsøeDavid MeyreEleanor WheelerKen OngEllen A NohrTanja G M VrijkotteGerard H KoppelmanRobert PlominPål R NjølstadGeorge D DedoussisPhilippe FroguelThorkild I A SørensenBo JacobssonRachel M FreathyBabette S ZemelOlli RaitakariMartine VrijheidBjarke FeenstraLeo-Pekka LyytikäinenHarold SniederHolger KirstenPatrick G HoltJoachim HeinrichElisabeth WidénJordi SunyerDorret I BoomsmaMarjo-Riitta JärvelinAntje KörnerGeorge Davey SmithJens-Christian HolmMustafa AtalayClare MurrayHans BisgaardMark I McCarthynull nullVincent W V JaddoeStruan F A GrantJanine F Felix

Published in: PLoS genetics (2020)

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 near NEDD4L and SLC45A3, 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 (Rg 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.