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The genetic architecture of sporadic and multiple consecutive miscarriage.
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; Børglum, Anders D; Gordon, Scott D; Bybjerg-Grauholm, Jonas; Helgeland, Øyvind; 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; Njølstad, Pål 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.
Afiliação
  • Laisk T; Department of Obstetrics and Gynecology, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. triin.laisk@ut.ee.
  • Soares ALG; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia. triin.laisk@ut.ee.
  • Ferreira T; Competence Centre on Health Technologies, Tartu, Estonia. triin.laisk@ut.ee.
  • Painter JN; MRC Integrated Epidemiology Unit at the University of Bristol, Bristol, UK.
  • Censin JC; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Laber S; Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK.
  • Bacelis J; QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
  • Chen CY; Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK.
  • Lepamets M; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Lin K; Big Data Institute, Li Ka Shing Center for Health for Health Information and Discovery, Oxford University, Oxford, UK.
  • Liu S; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Millwood IY; Department of Obstetrics and Gynecology, Sahlgrenska University Hospital Östra, Gothenburg, Sweden.
  • Ramu A; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Southcombe J; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Andersen MS; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Yang L; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Becker CM; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
  • Børglum AD; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Gordon SD; BGI-Shenzhen, Shenzhen, 518083, Guangdong, China.
  • Bybjerg-Grauholm J; Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark.
  • Helgeland Ø; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Hougaard DM; Medical Research Council Population Health Research Unit (PHRU), University of Oxford, Oxford, UK.
  • Jin X; Department of Genetics, Washington University in St. Louis, Saint Louis, MO, USA.
  • Johansson S; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.
  • Juodakis J; Department of Endocrinology, Odense University Hospital, Odense, Denmark.
  • Kartsonaki C; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Kukushkina V; Medical Research Council Population Health Research Unit (PHRU), University of Oxford, Oxford, UK.
  • Lind PA; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.
  • Metspalu A; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
  • Montgomery GW; Department of Biomedicine and Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
  • Morris AP; Center for Genomics and Personalized Medicine, Aarhus University and University Hospital, Aarhus, Denmark.
  • Mors O; QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
  • Mortensen PB; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
  • Njølstad PR; Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  • Nordentoft M; Department of Genetics and Bioinformatics, Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway.
  • Nyholt DR; KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
  • Lippincott M; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
  • Seminara S; Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
  • Salumets A; BGI-Shenzhen, Shenzhen, 518083, Guangdong, China.
  • Snieder H; School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China.
  • Zondervan K; KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
  • Werge T; Department of Medical Genetics, Haukeland University Hospital, N-5021, Bergen, Norway.
  • Chen Z; Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Conrad DF; Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Jacobsson B; Medical Research Council Population Health Research Unit (PHRU), University of Oxford, Oxford, UK.
  • Li L; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Martin NG; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
  • Neale BM; QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
  • Nielsen R; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Walters RG; University of Queensland, St Lucia, QLD, Australia.
Nat Commun ; 11(1): 5980, 2020 11 25.
Article em En | MEDLINE | ID: mdl-33239672
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Placenta / Aborto Espontâneo / Aborto Habitual / Predisposição Genética para Doença Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Aged / Female / Humans / Middle aged / Pregnancy Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Placenta / Aborto Espontâneo / Aborto Habitual / Predisposição Genética para Doença Tipo de estudo: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adult / Aged / Female / Humans / Middle aged / Pregnancy Idioma: En Ano de publicação: 2020 Tipo de documento: Article