ORCID Profile
0000-0002-3533-1999
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Publisher: Cold Spring Harbor Laboratory
Date: 12-03-2019
DOI: 10.1101/575167
Abstract: Miscarriage is a common complex trait that affects 10-25% of clinically confirmed pregnancies 1,2 . Here we present the first large-scale genetic association analyses with 69,118 cases from five different ancestries for sporadic miscarriage and 750 cases of European ancestry for recurrent miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association on chromosome 13 (rs146350366, minor allele frequency (MAF) 1.2%, P meta =3.2× -8 (CI) 1.2-1.6) for sporadic miscarriage in our European ancestry meta-analysis (50,060 cases and 174,109 controls), located near FGF9 involved in pregnancy maintenance 3 and progesterone production 4 . Additionally, we identified three genome-wide significant associations for recurrent miscarriage, including a signal on chromosome 9 (rs7859844, MAF=6.4%, P meta =1.3× -8 in controlling extravillous trophoblast motility 5 . We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability and, genetic correlation analyses. Our results implicate that miscarriage etiopathogenesis is partly driven by genetic variation related to gonadotropin regulation, placental biology and progesterone production.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2020
DOI: 10.1038/S41467-020-19742-5
Abstract: Miscarriage 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.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2017
DOI: 10.1038/NG.3743
Location: United States of America
No related grants have been discovered for Margaret Lippincott.