GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.
Alexessander Couto AlvesN Maneka G De SilvaVille KarhunenUlla SovioShikta DasH Rob TaalNicole M WarringtonAlexandra M LewinMarika A KaakinenDiana L CousminerElisabeth ThieringNicholas John TimpsonTom A BondEstelle LowryChristopher D BrownXavier EstivilVirpi LindiJonathan P BradfieldFrank GellerDoug SpeedLachlan J M CoinMarie LohSheila J BartonLawrence J BeilinHans BisgaardKlaus BønnelykkeRohia AliliIda J HatoumKatharina SchrammRufus CartwrightMarie Aline CharlesVincenzo SalernoKarine ClémentAnnique A J Claringbouldnull nullCornelia M Van DuijnElena MoltchanovaJohan G ErikssonCathy ElksBjarke FeenstraClaudia FlexederStephen FranksTimothy M FraylingRachel M FreathyPaul ElliottElisabeth WidenHakon H HakonarsonAndrew T HattersleyAlina RodriguezMarco BanterleJoachim HeinrichBarbara HeudeJohn W HollowayAlbert HofmanElina HyppӧnenHazel M InskipLee M KaplanAsa K HedmanEsa LääräHolger ProkischHarald GrallertTimo A LakkaDebbie A LawlorMads MelbyeTarunveer Singh AhluwaliaMarcella MarinelliIona Y MillwoodLyle J PalmerCraig E PennellJohn R B PerrySusan M RingMarkku J SavolainenFernando RivadeneiraMarie StandlJordi SunyerCarla M T TieslerAndre G UitterlindenWilliam SchierdingJustin Martin O'SullivanInga ProkopenkoKarl-Heinz HerzigGeorge Davey SmithPaul O'ReillyJanine F FelixJessica L BuxtonAlexandra I F BlakemoreKen K OngVincent W V JaddoeStruan F A GrantSylvain SebertMark I McCarthyMarjo-Riitta Jarvelinnull nullPublished in: Science advances (2019)
Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.