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dc.contributor.authorHorikoshi, Men
dc.contributor.authorBeaumont, RNen
dc.contributor.authorDay, Felixen
dc.contributor.authorWarrington, NMen
dc.contributor.authorKooijman, MNen
dc.contributor.authorFernandez-Tajes, Jen
dc.contributor.authorFeenstra, Ben
dc.contributor.authorvan Zuydam, NRen
dc.contributor.authorGaulton, KJen
dc.contributor.authorGrarup, Nen
dc.contributor.authorBradfield, JPen
dc.contributor.authorStrachan, DPen
dc.contributor.authorLi-Gao, Ren
dc.contributor.authorAhluwalia, TSen
dc.contributor.authorKreiner, Een
dc.contributor.authorRueedi, Ren
dc.contributor.authorLyytikäinen, L-Pen
dc.contributor.authorCousminer, DLen
dc.contributor.authorWu, Yen
dc.contributor.authorThiering, Een
dc.contributor.authorWang, CAen
dc.contributor.authorHave, CTen
dc.contributor.authorHottenga, J-Jen
dc.contributor.authorVilor-Tejedor, Nen
dc.contributor.authorJoshi, PKen
dc.contributor.authorBoh, ETHen
dc.contributor.authorNtalla, Ien
dc.contributor.authorPitkänen, Nen
dc.contributor.authorMahajan, Aen
dc.contributor.authorvan Leeuwen, EMen
dc.contributor.authorJoro, Ren
dc.contributor.authorLagou, Ven
dc.contributor.authorNodzenski, Men
dc.contributor.authorDiver, LAen
dc.contributor.authorZondervan, KTen
dc.contributor.authorBustamante, Men
dc.contributor.authorMarques-Vidal, Pen
dc.contributor.authorMercader, JMen
dc.contributor.authorBennett, AJen
dc.contributor.authorRahmioglu, Nen
dc.contributor.authorNyholt, DRen
dc.contributor.authorMa, RCWen
dc.contributor.authorTam, CHTen
dc.contributor.authorTam, WHen
dc.contributor.authorCHARGE Consortium Hematology Working Group,en
dc.contributor.authorGanesh, SKen
dc.contributor.authorvan Rooij, FJAen
dc.contributor.authorJones, SEen
dc.contributor.authorLoh, P-Ren
dc.contributor.authorRuth, KSen
dc.contributor.authorTuke, MAen
dc.contributor.authorTyrrell, Jen
dc.contributor.authorWood, ARen
dc.contributor.authorYaghootkar, Hen
dc.contributor.authorScholtens, DMen
dc.contributor.authorPaternoster, Len
dc.contributor.authorProkopenko, Ien
dc.contributor.authorKovacs, Pen
dc.contributor.authorAtalay, Men
dc.contributor.authorWillems, Saraen
dc.contributor.authorPanoutsopoulou, Ken
dc.contributor.authorWang, Xen
dc.contributor.authorCarstensen, Len
dc.contributor.authorGeller, Fen
dc.contributor.authorSchraut, KEen
dc.contributor.authorMurcia, Men
dc.contributor.authorvan Beijsterveldt, CEMen
dc.contributor.authorWillemsen, Gen
dc.contributor.authorAppel, EVRen
dc.contributor.authorFonvig, CEen
dc.contributor.authorTrier, Cen
dc.contributor.authorTiesler, CMTen
dc.contributor.authorStandl, Men
dc.contributor.authorKutalik, Zen
dc.contributor.authorBonàs-Guarch, Sen
dc.contributor.authorHougaard, DMen
dc.contributor.authorSánchez, Fen
dc.contributor.authorTorrents, Den
dc.contributor.authorWaage, Jen
dc.contributor.authorHollegaard, MVen
dc.contributor.authorde Haan, HGen
dc.contributor.authorRosendaal, FRen
dc.contributor.authorMedina-Gomez, Cen
dc.contributor.authorRing, SMen
dc.contributor.authorHemani, Gen
dc.contributor.authorMcMahon, Gen
dc.contributor.authorRobertson, NRen
dc.contributor.authorGroves, CJen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorLuan, Jian'anen
dc.contributor.authorScott, Roberten
dc.contributor.authorZhao, Jing Huaen
dc.contributor.authorMentch, FDen
dc.contributor.authorMacKenzie, SMen
dc.contributor.authorReynolds, RMen
dc.contributor.authorEarly Growth Genetics (EGG) Consortium,en
dc.contributor.authorLowe, WLen
dc.contributor.authorTönjes, Aen
dc.contributor.authorStumvoll, Men
dc.contributor.authorLindi, Ven
dc.contributor.authorLakka, TAen
dc.contributor.authorvan Duijn, CMen
dc.contributor.authorKiess, Wen
dc.contributor.authorKörner, Aen
dc.contributor.authorSørensen, TIAen
dc.contributor.authorNiinikoski, Hen
dc.contributor.authorPahkala, Ken
dc.contributor.authorRaitakari, OTen
dc.contributor.authorZeggini, Een
dc.contributor.authorDedoussis, GVen
dc.contributor.authorTeo, Y-Yen
dc.contributor.authorSaw, S-Men
dc.contributor.authorMelbye, Men
dc.contributor.authorCampbell, Hen
dc.contributor.authorWilson, JFen
dc.contributor.authorVrijheid, Men
dc.contributor.authorde Geus, EJCNen
dc.contributor.authorBoomsma, DIen
dc.contributor.authorKadarmideen, HNen
dc.contributor.authorHolm, J-Cen
dc.contributor.authorHansen, Ten
dc.contributor.authorSebert, Sen
dc.contributor.authorHattersley, ATen
dc.contributor.authorBeilin, LJen
dc.contributor.authorNewnham, JPen
dc.contributor.authorPennell, CEen
dc.contributor.authorHeinrich, Jen
dc.contributor.authorAdair, LSen
dc.contributor.authorBorja, JBen
dc.contributor.authorMohlke, KLen
dc.contributor.authorEriksson, JGen
dc.contributor.authorWidén, Een
dc.contributor.authorKähönen, Men
dc.contributor.authorViikari, JSen
dc.contributor.authorLehtimäki, Ten
dc.contributor.authorVollenweider, Pen
dc.contributor.authorBønnelykke, Ken
dc.contributor.authorBisgaard, Hen
dc.contributor.authorMook-Kanamori, DOen
dc.contributor.authorHofman, Aen
dc.contributor.authorRivadeneira, Fen
dc.contributor.authorUitterlinden, AGen
dc.contributor.authorPisinger, Cen
dc.contributor.authorPedersen, Oen
dc.contributor.authorPower, Cen
dc.contributor.authorHyppönen, Een
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorHakonarson, Hen
dc.contributor.authorDavies, Een
dc.contributor.authorWalker, BRen
dc.contributor.authorJaddoe, VWVen
dc.contributor.authorJärvelin, M-Ren
dc.contributor.authorGrant, SFAen
dc.contributor.authorVaag, AAen
dc.contributor.authorLawlor, DAen
dc.contributor.authorFrayling, TMen
dc.contributor.authorSmith, GDen
dc.contributor.authorMorris, APen
dc.contributor.authorOng, Kennethen
dc.contributor.authorFelix, JFen
dc.contributor.authorTimpson, NJen
dc.contributor.authorPerry, Johnen
dc.contributor.authorEvans, DMen
dc.contributor.authorMcCarthy, MIen
dc.contributor.authorFreathy, RMen
dc.date.accessioned2016-12-01T11:29:26Z
dc.date.available2016-12-01T11:29:26Z
dc.date.issued2016-10-13en
dc.identifier.issn0028-0836
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/261375
dc.description.abstractBirth 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 ($\textit{P}$  < 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 ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 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 ($\textit{P}$ = 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.
dc.description.sponsorshipFor a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust.
dc.languageENGen
dc.publisherNature Publishing Group
dc.subjectmetabolic disordersen
dc.subjectquantitative traiten
dc.subjectintrauterine growthen
dc.subjecthypertensionen
dc.subjectgenome-wide association studiesen
dc.titleGenome-wide associations for birth weight and correlations with adult diseaseen
dc.typeArticle
prism.endingPage252
prism.issueIdentifier7624en
prism.publicationDate2016en
prism.publicationNameNatureen
prism.startingPage248
prism.volume538en
dc.identifier.doi10.17863/CAM.6542
dcterms.dateAccepted2016-09-22en
rioxxterms.versionofrecord10.1038/nature19806en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-10-13en
dc.contributor.orcidDay, Felix [0000-0003-3789-7651]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidLuan, Jian'an [0000-0003-3137-6337]
dc.contributor.orcidZhao, Jing Hua [0000-0003-4930-3582]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.identifier.eissn1476-4687
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idMRC (MC_UU_12015/1)
cam.issuedOnline2016-09-28en
rioxxterms.freetoread.startdate2017-03-28


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