6533b82ffe1ef96bd1294710
RESEARCH PRODUCT
Genome-wide associations for birth weight and correlations with adult disease
Anubha MahajanGeorge McmahonCharlotta PisingerTimothy M. FraylingElisabeth M. Van LeeuwenFelix R. DayVirpi LindiAllan VaagAllan VaagDebbie A LawlorNatalie R. Van ZuydamPeter KovacsDavid TorrentsBjarke FeenstraPeter VollenweiderDavid P. StrachanKrina T. ZondervanJohn R. B. PerryJorma ViikariPedro Marques-vidalKalliope PanoutsopoulouRuifang Li-gaoJuan Fernández-tajesCarolina Medina-gomezNicole M. WarringtonNicole M. WarringtonJosep M. MercaderAntje KörnerDavid M. EvansDavid M. EvansAlbert HofmanHans BisgaardAmanda J. BennettEleanor DaviesLinda S. AdairOluf PedersenMustafa AtalaySylvain SebertSylvain SebertYing WuHaja N. KadarmideenRonald C.w. MaLawrence J. BeilinDavid M. HougaardDiana L. CousminerDiana L. CousminerDiana L. CousminerLouise A. DiverJing Hua ZhaoNilufer RahmiogluPeter K. JoshiNeil R. RobertsonJohannes WaageHugoline G. De HaanJens-christian HolmDale R. NyholtTorben HansenSara M. WillemsSílvia Bonàs-guarchCarol A. WangRico RueediRico RueediLavinia PaternosterJames F. WilsonCilius Esmann FonvigLeo-pekka LyytikäinenHanieh YaghootkarMomoko HorikoshiGonneke WillemsenDennis O. Mook-kanamoriLisbeth CarstensenMariona BustamanteEmil V. R. AppelChristian Theil HaveRebecca M. ReynoldsNiels GrarupSeang-mei SawYik Ying TeoBrian R. WalkerAnke TönjesChristopher J. GrovesAndrew P. MorrisAndrew P. MorrisAndrew P. MorrisKatja PahkalaMarjolein N. KooijmanKyle J. GaultonKyle J. GaultonEskil KreinerMichael StumvollEleftheria ZegginiVincent W. V. JaddoeZoltán KutalikZoltán KutalikScott M. MackenzieGeorge Davey SmithChristine PowerDenise M. ScholtensJoachim HeinrichSamuel E. JonesWilliam L. LoweEco J. C. De GeusEco J. C. De GeusJonathan P. BradfieldAndrew T. HattersleyJanine F. FelixWing Hung TamFrits R. RosendaalWieland KiessClaudia H. T. TamInga ProkopenkoInga ProkopenkoTerho LehtimäkiFrank D. MentchMarjo-riitta JärvelinStruan F.a. GrantSanthi K. GaneshFernando RivadeneiraThorkild I. A. SørensenAndré G. UitterlindenMarie StandlJian'an LuanGibran HemaniMarcus A. TukeAndrew R. WoodRobert A. ScottCæcilie TrierTarunveer S. AhluwaliaTarunveer S. AhluwaliaMichael NodzenskiJouke-jan HottengaKen K. OngPo-ru LohNicholas J. TimpsonGeorge DedoussisFriman SánchezMark I. MccarthyMark I. MccarthyMark I. MccarthyFrank GellerHarri NiinikoskiMartine VrijheidHakon HakonarsonJohn P. NewnhamXu WangElina HyppönenElina HyppönenJohan ErikssonJohan G. ErikssonCraig E. PennellNiina PitkänenRachel M. FreathyRachel M. FreathyElisabeth WidenJudith B. BorjaKaren L. MohlkeMads MelbyeMads MelbyeMads MelbyeCarla M. T. TieslerSusan M. RingJessica TyrrellElisabeth ThieringTimo A. LakkaEileen Tai-hui BohOlli T. RaitakariNicholas J. WarehamMario MurciaNatalia Vilor-tejedorKatherine S. RuthDorret I. BoomsmaHarry CampbellVasiliki LagouVasiliki LagouRobin N BeaumontKlaus BønnelykkeClaudia LangenbergCatharina E. M. Van BeijsterveldtMika KähönenMads V. HollegaardFrank J.a. Van RooijKatharina E. SchrautIoanna NtallaIoanna NtallaRaimo JoroCornelia M. Van Duijnsubject
Male0301 basic medicineNetherlands Twin Register (NTR)AgingDatasets as TopicPhysiologyBlood PressureGenome-wide association studyCoronary Artery DiseaseType 2 diabetesBioinformaticsCHARGE Consortium Hematology Working GroupCohort Studies0302 clinical medicineBirth WeightInsulinGlucose homeostasis030212 general & internal medicineeducation.field_of_studyMultidisciplinaryAnthropometry3. Good healthPhenotype/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_beingFemaleGlycogenSignal TransductionAdulthypertensionGenotypeGeneral Science & TechnologyBirth weightintrauterine growthPopulationQuantitative trait locusBiologyArticlequantitative traitGenomic Imprinting03 medical and health sciencesFetusSDG 3 - Good Health and Well-beingEarly Growth Genetics (EGG) ConsortiumMD MultidisciplinaryGenetic variation/dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_medicineHumansmetabolic disordersGenetic Predisposition to DiseaseeducationgenomeGenetic associationGenetic Variationbirth weightta3121Chromatin Assembly and Disassemblymedicine.diseaseta3123Glucose030104 developmental biologyDiabetes Mellitus Type 2Genetic Locigenome-wide association studiesadult diseaseGenome-Wide Association Studydescription
Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-10-13 |