| Title | The genetic architecture of sporadic and multiple consecutive miscarriage |
| Authors | 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. |
| Affiliation | Univ Tartu, Inst Clin Med, Dept Obstet & Gynecol, Tartu, Estonia Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia Competence Ctr Hlth Technol, Tartu, Estonia Univ Bristol, MRC Integrated Epidemiol Unit, Bristol, Avon, England Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Hlth Informat & Discovery, Oxford, England QIMR Berghofer Med Res Inst, Herston, Qld, Australia Univ Oxford, Wellcome Ctr Human Genet, Oxford, England Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Cambridge, MA 02142 USA Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-2200 Copenhagen, Denmark Univ Oxford, Med Res Council, Populat Hlth Res Unit PHRU, Oxford, England Washington Univ, Dept Genet, St Louis, MO 63110 USA Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England Odense Univ Hosp, Dept Endocrinol, Odense, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res, iPSYCH, Aarhus, Denmark Aarhus Univ, Dept Biomed, iSEQ, Aarhus, Denmark Aarhus Univ, Ctr Integrat Sequencing, iSEQ, Aarhus, Denmark Aarhus Univ, Ctr Genom & Personalized Med, Aarhus, Denmark Univ Hosp, Aarhus, Denmark Statens Serum Inst, Dept Congenital Disorders, Copenhagen, Denmark Norwegian Inst Publ Hlth, Dept Genet & Bioinformat, Hlth Data & Digitalisat, Oslo, Norway Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, N-5020 Bergen, Norway South China Univ Technol, Sch Med, Guangzhou 510006, Guangdong, Peoples R China Haukeland Hosp, Dept Med Genet, N-5021 Bergen, Norway Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden Univ Queensland, St Lucia, Qld, Australia Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England Aarhus Univ Hosp Psychiat, Psychosis Res Unit, Psychiat, Aarhus, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, Denmark Haukeland Hosp, Dept Pediat, Bergen, Norway Copenhagen Univ Hosp, Mental Hlth Ctr Copenhagen, Mental Hlth Serv Capital Reg Denmark, Copenhagen, Denmark Queensland Univ Technol, Fac Hlth, Sch Biomed Sci, Brisbane, Qld, Australia Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA Univ Tartu, Inst Bio & Translat Med, Tartu, Estonia Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland Helsinki Univ Hosp, Helsinki, Finland Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands Mental Hlth Serv Copenhagen, Inst Biol Psychiat, MHC Sct Hans, Roskilde, Denmark Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark Peking Univ, Hlth Sci Ctr, Dept Epidemiol & Biostat, Beijing, Peoples R China Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA Univ Copenhagen, Ctr GeoGenet, Nat Hist Museum Denmark, Copenhagen, Denmark Bristol Natl Inst Hlth Res, Biomed Res Ctr, Bristol, Avon, England Broad Inst, Program Med & Populat Genet, Boston, MA 02142 USA |
| Keywords | GENOME-WIDE ASSOCIATION BODY-MASS INDEX MENDELIAN RANDOMIZATION PREGNANCY LOSS RISK METAANALYSIS VARIANTS TERMINOLOGY STILLBIRTH REGRESSION |
| Issue Date | 25-Dec-2020 |
| Publisher | NATURE COMMUNICATIONS |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/599922 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-020-19742-5 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
