Year: 2019
Type: preprint
Study design: Observational Study
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.
DOI: 10.1101/575167
Authors: Triin Laisk, Ana Luiza G Soares, Teresa Ferreira, Jodie N Painter, Samantha Laber, Jonas Bacelis, Chia-Yen Chen, Maarja Lepamets, Kuang Lin, Siyang Liu, Iona Y Millwood, Avinash Ramu, Jennifer Southcombe, Marianne S Andersen, Ling Yang, Christian M Becker, Scott D Gordon, Jonas Bybjerg-Grauholm, Øyvind Helgeland, David M Hougaard, Xin Jin, Stefan Johansson, Julius Juodakis, Christiana Kartsonaki, Viktorija Kukushkina, Lifelines Cohort Study, Penelope A Lind, Andres Metspalu, Grant W Montgomery, Andrew P Morris, Preben B Mortensen, Pål R Njølstad, Dale R Nyholt, Margaret Lippincott, Stephanie Seminara, Andres Salumets, Harold Snieder, Krina Zondervan, Zhengming Chen, Donald F Conrad, Bo Jacobsson, Liming Li, Nicholas G Martin, Benjamin M Neale, Rasmus Nielsen, Robin G Walters, Ingrid Granne, Sarah E Medland, Reedik Mägi, Deborah A Lawlor, Cecilia M Lindgren
Institutions: Competence Centre on Health Technologies (Estonia), University of Tartu, University of Bristol, MRC Integrative Epidemiology Unit, University of Oxford, QIMR Berghofer Medical Research Institute, Centre for Human Genetics, Sahlgrenska University Hospital, Broad Institute, Massachusetts General Hospital, BGI Group (China), University of Copenhagen, MRC Population Health Research Unit, Washington University in St. Louis, Odense University Hospital, Statens Serum Institut, Lundbeck Foundation, Norwegian Institute of Public Health, University of Bergen, South China University of Technology, Haukeland University Hospital, University of Gothenburg, Lifelines, The University of Queensland, University of Liverpool, Aarhus University, Queensland University of Technology, University of Helsinki, Helsinki University Hospital, University Medical Center Groningen, University of Groningen, Peking University, Natural History Museum of Denmark, University of California, Berkeley, NIHR Bristol Biomedical Research Centre
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: European Commission
OpenAlex ID: W2921291238