The genetic architecture of sporadic and multiple consecutive miscarriage

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dc.contributor.authorLaisk, Triin
dc.contributor.authorSoares, Ana Luiza G.
dc.contributor.authorLindgren, Cecilia M.
dc.contributor.authorFerreira, Teresa
dc.contributor.authorPainter, Jodie N.
dc.contributor.authorCensin, Jenny C.
dc.contributor.authorLaber, Samantha
dc.contributor.authorBacelis, Jonas
dc.contributor.authorChen, Chia-Yen
dc.contributor.authorLepamets, Maarja
dc.contributor.authorLawlor, Deborah A.
dc.contributor.authorMägi, Reedik
dc.contributor.authorMedland, Sarah E.
dc.contributor.authorGranne, Ingrid
dc.contributor.authorWalters, Robin G.
dc.contributor.authorNielsen, Rasmus
dc.contributor.authorNeale, Benjamin M.
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorLi, Liming
dc.contributor.authorJacobsson, Bo
dc.contributor.authorConrad, Donald F.
dc.contributor.authorChen, Zhengming
dc.contributor.authorWerge, Thomas
dc.contributor.authorZondervan, Krina
dc.contributor.authorSnieder, Harold
dc.contributor.authorSalumets, Andres
dc.contributor.authorSeminara, Stephanie
dc.contributor.authorLippincott, Margaret
dc.contributor.authorNyholt, Dale R.
dc.contributor.authorNordentoft, Merete
dc.contributor.authorNjølstad, Pål R.
dc.contributor.authorMortensen, Preben B.
dc.contributor.authorMors, Ole
dc.contributor.authorMorris, Andrew P.
dc.contributor.authorMontgomery, Grant W.
dc.contributor.authorMetspalu, Andres
dc.contributor.authorLind, Penelope A.
dc.contributor.authorKukushkina, Viktorija
dc.contributor.authorKartsonaki, Christiana
dc.contributor.authorJuodakis, Julius
dc.contributor.authorJohansson, Stefan
dc.contributor.authorJin, Xin
dc.contributor.authorHougaard, David M.
dc.contributor.authorHelgeland, Øyvind
dc.contributor.authorBybjerg-Grauholm, Jonas
dc.contributor.authorGordon, Scott D.
dc.contributor.authorBørglum, Anders D.
dc.contributor.authorBecker, Christian M.
dc.contributor.authorYang, Ling
dc.contributor.authorAndersen, Marianne S.
dc.contributor.authorSouthcombe, Jennifer
dc.contributor.authorRamu, Avinash
dc.contributor.authorMillwood, Iona Y.
dc.contributor.authorLiu, Siyang
dc.contributor.authorLin, Kuang
dc.date.accessioned2020-11-30T10:48:48Z
dc.date.available2020-11-30T10:48:48Z
dc.date.issued2020-11-25
dc.description.abstractMiscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10−8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10−8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10−9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10−8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.et
dc.identifier.urihttps://doi.org/10.1038/s41467-020-19742-5
dc.identifier.urihttp://hdl.handle.net/10062/70511
dc.language.isoenget
dc.publisherNature Communicationset
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/692065///WIDENLIFEet
dc.relation.ispartofseriesNat Commun 11.;5980 (2020)
dc.rightsinfo:eu-repo/semantics/openAccesset
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleThe genetic architecture of sporadic and multiple consecutive miscarriageet
dc.typeinfo:eu-repo/semantics/articleet

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