Vogelezang, SuzanneBradfield, Jonathan PAhluwalia, Tarunveer SCurtin, John ALakka, Timo AGrarup, NielsScholz, Markusvan der Most, Peter JMonnereau, ClaireStergiakouli, EvieHeiskala, AnniHorikoshi, MomokoFedko, Iryna OVilor-Tejedor, NataliaCousminer, Diana LStandl, MarieWang, Carol AViikari, JormaGeller, Frankiniguez, CarmenPitkanen, NiinaChesi, AlessandraBacelis, JonasYengo, LoicTorrent Quetglas, MatiesNtalla, IoannaHelgeland, ØyvindSelzam, SaskiaVonk, Judith MZafarmand, Mohammed HHeude, BarbaraFarooqi, Ismaa SadafAlyass, AkramBeaumont, Robin NHave, Christian TRzehak, PeterBilbao, Jose RamonSchnurr, Theresia MBarroso, InesBonnelykke, KlausBeilin, Lawrence JCarstensen, LisbethCharles, Marie-AlineChawes, BoClement, KarineClosa-Monasterolo, RicardoCustovic, AdnanEriksson, Johan GEscribano, JoaquinGroen-Blokhuis, MariaGrote, VeitGruszfeld, DariuszHakonarson, HakonHansen, TorbenHattersley, Andrew THollensted, MetteHottenga, Jouke-JanHyppönen, ElinaJohansson, StefanJoro, RaimoKähönen, MikaKarhunen, VilleKiess, WielandKnight, Bridget AKoletzko, BertholdKüehnapfel, AndreasLandgraf, KathrinLanghendries, Jean-PaulLehtimäki, TerhoLeinonen, Jaakko TLi, AihualiLindi, VirpiLowry, EstelleBustamante, MarionaMedina-Gomez, CarolinaMelbye, MadsMichaelsen, Kim FMorgen, Camilla SMori, Trevor ANielsen, Tenna RHNiinikoski, HarriOldehinkel, Albertine JPahkala, KatjaPanoutsopoulou, KalliopePedersen, OlufPennell, Craig EPower, ChristineReijneveld, Sijmen ARivadeneira, FernandoSimpson, AngelaSly, Peter DStokholm, JakobTeo, Kook KThiering, ElisabethTimpson, Nicholas JUitterlinden, Andre Gvan Beijsterveldt, Catharina E. Mvan Schaik, Barbera D. CVaudel, MarcVerduci, ElviraVinding, Rebecca KVogel, MandyZeggini, EleftheriaSebert, SylvainLind, Mads VBrown, Christopher DSanta-Marina, LoretoReischl, EvaFrithioff-Bøjsøe, ChristineMeyre, DavidWheeler, EleanorOng, KenNohr, Ellen AVrijkotte, Tanja G. MKoppelman, Gerard HPlomin, RobertNjølstad, Pal RDedoussis, George DFroguel, PhilippeSorensen, Thorkild I. AJacobsson, BoFreathy, Rachel MZemel, Babette SRaitakari, OlliVrijheid, MartineFeenstra, BjarkeLyytikäinen, Leo-PekkaSnieder, HaroldKirsten, HolgerHolt, Patrick GHeinrich, JoachimWiden, ElisabethSunyer, JordiBoomsma, Dorret IJärvelin, Marjo-RiittaKöerner, AntjeDavey Smith, GeorgeHolm, Jens-ChristianAtalay, MustafaMurray, ClareBisgaard, HansMcCarthy, Mark IEarly Growth Genetics ConsortiumJaddoe, Vincent WVGrant, Struan FAFelix, Janine F2024-09-132024-09-132020-10Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, et al. Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genet. 2020 Oct;16(10):e1008718.1553-7404http://hdl.handle.net/20.500.13003/9198https://hdl.handle.net/20.500.12105/23028The 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.enghttp://creativecommons.org/licenses/by/4.0/Cardiovascular DiseasesChildDiabetes Mellitus, Type 2Genetic Predisposition to DiseaseCardiometabolic Risk FactorsAdultHumansMendelian Randomization AnalysisChild, PreschoolAdolescentWaist-Hip RatioBlood PressureMonosaccharide Transport ProteinsMaleMenarcheNedd4 Ubiquitin Protein LigasesFemaleBody Mass IndexGenome-Wide Association Studyresearch articleAttribution 4.0 International330450051610e100871810.1371/journal.pgen.1008718PloS Geneticsopen accessÍndice de Masa CorporalAnálisis de la Aleatorización MendelianaRelación Cintura-CaderaFactores de Riesgo CardiometabólicoPredisposición Genética a la EnfermedadFemeninoUbiquitina-Proteína Ligasas Nedd4Proteínas de Transporte de MonosacáridosAdolescenteMasculinoMenarquiaEstudio de Asociación del Genoma CompletoPreescolarPresión SanguíneaHumanosDiabetes Mellitus Tipo 2Enfermedades CardiovascularesNiñoAdulto2-s2.0-85092931223582197600001L2008348102