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Influence of autozygosity on common disease risk across the phenotypic spectrum
Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F(ROH)) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184)...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580289/ https://www.ncbi.nlm.nih.gov/pubmed/37757828 http://dx.doi.org/10.1016/j.cell.2023.08.028 |
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author | Malawsky, Daniel S. van Walree, Eva Jacobs, Benjamin M. Heng, Teng Hiang Huang, Qin Qin Sabir, Ataf H. Rahman, Saadia Sharif, Saghira Malik Khan, Ahsan Mirkov, Maša Umićević Kuwahara, Hiroyuki Gao, Xin Alkuraya, Fowzan S. Posthuma, Danielle Newman, William G. Griffiths, Christopher J. Mathur, Rohini van Heel, David A. Finer, Sarah O’Connell, Jared Martin, Hilary C. |
author_facet | Malawsky, Daniel S. van Walree, Eva Jacobs, Benjamin M. Heng, Teng Hiang Huang, Qin Qin Sabir, Ataf H. Rahman, Saadia Sharif, Saghira Malik Khan, Ahsan Mirkov, Maša Umićević Kuwahara, Hiroyuki Gao, Xin Alkuraya, Fowzan S. Posthuma, Danielle Newman, William G. Griffiths, Christopher J. Mathur, Rohini van Heel, David A. Finer, Sarah O’Connell, Jared Martin, Hilary C. |
author_sort | Malawsky, Daniel S. |
collection | PubMed |
description | Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F(ROH)) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F(ROH). Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F(ROH) and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%–18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity. |
format | Online Article Text |
id | pubmed-10580289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105802892023-10-18 Influence of autozygosity on common disease risk across the phenotypic spectrum Malawsky, Daniel S. van Walree, Eva Jacobs, Benjamin M. Heng, Teng Hiang Huang, Qin Qin Sabir, Ataf H. Rahman, Saadia Sharif, Saghira Malik Khan, Ahsan Mirkov, Maša Umićević Kuwahara, Hiroyuki Gao, Xin Alkuraya, Fowzan S. Posthuma, Danielle Newman, William G. Griffiths, Christopher J. Mathur, Rohini van Heel, David A. Finer, Sarah O’Connell, Jared Martin, Hilary C. Cell Article Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F(ROH)) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F(ROH). Within this group in G&H+UK Biobank, we found experiment-wide significant associations between F(ROH) and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%–18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity. Cell Press 2023-10-12 /pmc/articles/PMC10580289/ /pubmed/37757828 http://dx.doi.org/10.1016/j.cell.2023.08.028 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Malawsky, Daniel S. van Walree, Eva Jacobs, Benjamin M. Heng, Teng Hiang Huang, Qin Qin Sabir, Ataf H. Rahman, Saadia Sharif, Saghira Malik Khan, Ahsan Mirkov, Maša Umićević Kuwahara, Hiroyuki Gao, Xin Alkuraya, Fowzan S. Posthuma, Danielle Newman, William G. Griffiths, Christopher J. Mathur, Rohini van Heel, David A. Finer, Sarah O’Connell, Jared Martin, Hilary C. Influence of autozygosity on common disease risk across the phenotypic spectrum |
title | Influence of autozygosity on common disease risk across the phenotypic spectrum |
title_full | Influence of autozygosity on common disease risk across the phenotypic spectrum |
title_fullStr | Influence of autozygosity on common disease risk across the phenotypic spectrum |
title_full_unstemmed | Influence of autozygosity on common disease risk across the phenotypic spectrum |
title_short | Influence of autozygosity on common disease risk across the phenotypic spectrum |
title_sort | influence of autozygosity on common disease risk across the phenotypic spectrum |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580289/ https://www.ncbi.nlm.nih.gov/pubmed/37757828 http://dx.doi.org/10.1016/j.cell.2023.08.028 |
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