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The genetic architecture of sporadic and multiple consecutive miscarriage.

Laisk, Triin (author)
Soares, Ana Luiza G (author)
Ferreira, Teresa (author)
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Painter, Jodie N (author)
Censin, Jenny C (author)
Laber, Samantha (author)
Bacelis, Jonas (author)
Chen, Chia-Yen (author)
Lepamets, Maarja (author)
Lin, Kuang (author)
Liu, Siyang (author)
Millwood, Iona Y (author)
Ramu, Avinash (author)
Southcombe, Jennifer (author)
Andersen, Marianne S (author)
Yang, Ling (author)
Becker, Christian M (author)
Børglum, Anders D (author)
Gordon, Scott D (author)
Bybjerg-Grauholm, Jonas (author)
Helgeland, Øyvind (author)
Hougaard, David M (author)
Jin, Xin (author)
Johansson, Stefan (author)
Juodakis, Julius (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Kartsonaki, Christiana (author)
Kukushkina, Viktorija (author)
Lind, Penelope A (author)
Metspalu, Andres (author)
Montgomery, Grant W (author)
Morris, Andrew P (author)
Mors, Ole (author)
Mortensen, Preben B (author)
Njølstad, Pål R (author)
Nordentoft, Merete (author)
Nyholt, Dale R (author)
Lippincott, Margaret (author)
Seminara, Stephanie (author)
Salumets, Andres (author)
Snieder, Harold (author)
Zondervan, Krina (author)
Werge, Thomas (author)
Chen, Zhengming (author)
Conrad, Donald F (author)
Jacobsson, Bo, 1960 (author)
Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Li, Liming (author)
Martin, Nicholas G (author)
Neale, Benjamin M (author)
Nielsen, Rasmus (author)
Walters, Robin G (author)
Granne, Ingrid (author)
Medland, Sarah E (author)
Mägi, Reedik (author)
Lawlor, Deborah A (author)
Lindgren, Cecilia M (author)
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 (creator_code:org_t)
2020-11-25
2020
English.
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
Related links:
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https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)

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