Rachel M. FreathyDennis O. Mook-KanamoriUlla SovioInga ProkopenkoNicholas J. TimpsonDiane J. BerryNicole M. WarringtonElisabeth WidenJouke Jan HottengaMarika KaakinenLeslie A. LangeJonathan P. BradfieldMarjan KerkhofJulie A. MarshReedik MägiChih Mei ChenHelen N. LyonMirna KirinLinda S. AdairYurii S. AulchenkoAmanda J. BennettJudith B. BorjaNabila Bouatia-NajiPimphen CharoenLachlan J.M. CoinDiana L. CousminerEco J.C. De GeusPanos DeloukasPaul ElliottDavid M. EvansPhilippe FroguelBeate GlaserChristopher J. GrovesAnna Liisa HartikainenNeelam HassanaliJoel N. HirschhornAlbert HofmanJeff M.P. HollyElina HyppönenStavroula KanoniBridget A. KnightJaana LaitinenCecilia M. LindgrenWendy L. McArdlePaul F. O'ReillyCraig E. PennellDirkje S. PostmaAnneli PoutaAdaikalavan RamasamyNigel W. RaynerSusan M. RingFernando RivadeneiraBeverley M. ShieldsDavid P. StrachanIda SurakkaAnja TaanilaCarla TieslerAndre G. UitterlindenCornelia M. Van DuijnAlet H. WijgaGonneke WillemsenHaitao ZhangJianhua ZhaoJames F. WilsonEric A.P. SteegersAndrew T. HattersleyJohan G. ErikssonLeena PeltonenKaren L. MohlkeStruan F.A. GrantHakon HakonarsonUniversity of ExeterErasmus University Medical CenterImperial College LondonUniversity of OxfordWellcome Trust Centre for Human GeneticsMedical Research CouncilUCLUniversity of Western AustraliaHelsingin YliopistoVrije Universiteit AmsterdamOulun YliopistoThe University of North Carolina at Chapel HillThe Children's Hospital of PhiladelphiaUniversity of Groningen, University Medical Center GroningenHelmholtz Center Munich German Research Center for Environmental HealthKlinikum der Universitat MunchenChildren's Hospital BostonHarvard Medical SchoolUniversity of EdinburghUniversity of San CarlosCNRS Centre National de la Recherche ScientifiqueUniversity of LilleMahidol UniversityWellcome Trust Sanger InstituteHammersmith HospitalUniversity of BristolMassachusetts Institute of TechnologyHarokopio UniversityTyoterveyslaitosUniversity of Western Australia Faculty of Medicine and DentistryNational Institute for Health and WelfareNational Heart and Lung InstituteUniversity of LondonNational Institute of Public Health and the EnvironmentHelsinki University HospitalFolkhalsanNational Institute for Health and WelfareUniversity of Pennsylvania, School of MedicineUniversity Medical Center Groningen, Centre for Revalidation (Beatrix Children's Hospital)Churchill Hospital2018-09-242018-09-242010-05-01Nature Genetics. Vol.42, No.5 (2010), 430-43515461718106140362-s2.0-77951766379https://repository.li.mahidol.ac.th/handle/123456789/28728To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 × 10 35) and rs9883204 in ADCY5 (P = 7 × 10 15) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113g (95% CI 89-137g) lighter at birth than the 24% with zero or one alleles (P trend = 7 × 10 30). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy. © 2010 Nature America, Inc. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/ng.567