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  • Laisk, Triin (author)

The genetic architecture of sporadic and multiple consecutive miscarriage.

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-11-25
  • Springer Science and Business Media LLC,2020

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/298297
  • https://gup.ub.gu.se/publication/298297URI
  • https://doi.org/10.1038/s41467-020-19742-5DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

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  • Soares, Ana Luiza G (author)
  • Ferreira, Teresa (author)
  • Painter, Jodie N (author)
  • Censin, Jenny C (author)
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  • Hougaard, David M (author)
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  • Juodakis, JuliusGothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xjouju (author)
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  • Conrad, Donald F (author)
  • Jacobsson, Bo,1960Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xjacbo (author)
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  • Lawlor, Deborah A (author)
  • Lindgren, Cecilia M (author)
  • Göteborgs universitetInstitutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi (creator_code:org_t)

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  • In:Nature communications: Springer Science and Business Media LLC11:12041-1723

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