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The genetic architecture of sporadic and multiple consecutive miscarriage
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 m...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689465/ https://www.ncbi.nlm.nih.gov/pubmed/33239672 http://dx.doi.org/10.1038/s41467-020-19742-5 |
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| author | 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. Granne, Ingrid Medland, Sarah E. Mägi, Reedik Lawlor, Deborah A. Lindgren, Cecilia M. |
| author_facet | 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. Granne, Ingrid Medland, Sarah E. Mägi, Reedik Lawlor, Deborah A. Lindgren, Cecilia M. |
| author_sort | Laisk, Triin |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7689465 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-76894652020-12-03 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. Granne, Ingrid Medland, Sarah E. Mägi, Reedik Lawlor, Deborah A. Lindgren, Cecilia M. Nat Commun Article 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. Nature Publishing Group UK 2020-11-25 /pmc/articles/PMC7689465/ /pubmed/33239672 http://dx.doi.org/10.1038/s41467-020-19742-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article 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. Granne, Ingrid Medland, Sarah E. Mägi, Reedik Lawlor, Deborah A. Lindgren, Cecilia M. The genetic architecture of sporadic and multiple consecutive miscarriage |
| title | The genetic architecture of sporadic and multiple consecutive miscarriage |
| title_full | The genetic architecture of sporadic and multiple consecutive miscarriage |
| title_fullStr | The genetic architecture of sporadic and multiple consecutive miscarriage |
| title_full_unstemmed | The genetic architecture of sporadic and multiple consecutive miscarriage |
| title_short | The genetic architecture of sporadic and multiple consecutive miscarriage |
| title_sort | genetic architecture of sporadic and multiple consecutive miscarriage |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689465/ https://www.ncbi.nlm.nih.gov/pubmed/33239672 http://dx.doi.org/10.1038/s41467-020-19742-5 |
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