In:
Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-11-25)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-020-19742-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2020
detail.hit.zdb_id:
2553671-0
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