The genetic architecture of sporadic and multiple consecutive miscarriage

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Laisk , T , Soares , A L G , Ferreira , T , Painter , J N , Censin , J C , Laber , S , Bacelis , J , Chen , C-Y , Lepamets , M , Lin , K , Liu , S , Millwood , I Y , Ramu , A , Southcombe , J , Andersen , M S , Yang , L , Becker , C M , Borglum , A D , Gordon , S D , Bybjerg-Grauholm , J , Helgeland , O , Hougaard , D M , Jin , X , Johansson , S , Juodakis , J , Kartsonaki , C , Kukushkina , V , Lind , P A , Metspalu , A , Montgomery , G W , Morris , A P , Mors , O , Mortensen , P B , Njolstad , P R , Nordentoft , M , Nyholt , D R , Lippincott , M , Seminara , S , Salumets , A , Snieder , H , Zondervan , K , Werge , T , Chen , Z , Conrad , D F , Jacobsson , B , Li , L , Martin , N G , Neale , B M , Nielsen , R , Walters , R G , Granne , I , Medland , S E , Maegi , R , Lawlor , D A & Lindgren , C M 2020 , ' The genetic architecture of sporadic and multiple consecutive miscarriage ' , Nature Communications , vol. 11 , no. 1 , 5980 . https://doi.org/10.1038/s41467-020-19742-5

Title: The genetic architecture of sporadic and multiple consecutive miscarriage
Author: Laisk, Triin; Soares, Ana Luiza G.; Ferreira, Teresa; Painter, Jodie N.; Censin, Jenny C.; Laber, Samantha; Bacelis, Jonas; Chen, Chia-Yen; Lepamets, Maarja; Lin, Kuang; Liu, Siyang; Millwood, Iona Y.; Ramu, Avinash; Southcombe, Jennifer; Andersen, Marianne S.; Yang, Ling; Becker, Christian M.; Borglum, Anders D.; Gordon, Scott D.; Bybjerg-Grauholm, Jonas; Helgeland, Oyvind; Hougaard, David M.; Jin, Xin; Johansson, Stefan; Juodakis, Julius; Kartsonaki, Christiana; Kukushkina, Viktorija; Lind, Penelope A.; Metspalu, Andres; Montgomery, Grant W.; Morris, Andrew P.; Mors, Ole; Mortensen, Preben B.; Njolstad, Pal R.; Nordentoft, Merete; Nyholt, Dale R.; Lippincott, Margaret; Seminara, Stephanie; Salumets, Andres; Snieder, Harold; Zondervan, Krina; Werge, Thomas; Chen, Zhengming; Conrad, Donald F.; Jacobsson, Bo; Li, Liming; Martin, Nicholas G.; Neale, Benjamin M.; Nielsen, Rasmus; Walters, Robin G.; Granne, Ingrid; Medland, Sarah E.; Maegi, Reedik; Lawlor, Deborah A.; Lindgren, Cecilia M.
Contributor: University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2020-12-25
Language: eng
Number of pages: 12
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/324443
Abstract: Miscarriage is a common, complex trait affecting similar to 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 x 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 x 10(-8), OR=1.7; rs143445068, MAF=0.8%, P=5.2 x 10(-9), OR=3.4; rs183453668, MAF=0.5%, P=2.8 x 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.
Subject: GENOME-WIDE ASSOCIATION
BODY-MASS INDEX
MENDELIAN RANDOMIZATION
PREGNANCY LOSS
RISK
METAANALYSIS
VARIANTS
TERMINOLOGY
STILLBIRTH
REGRESSION
3111 Biomedicine
1184 Genetics, developmental biology, physiology
3123 Gynaecology and paediatrics
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