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Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits
The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2018
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220258/ https://www.ncbi.nlm.nih.gov/pubmed/30405126 http://dx.doi.org/10.1038/s41467-018-07070-8 |
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| author | Gilly, Arthur Suveges, Daniel Kuchenbaecker, Karoline Pollard, Martin Southam, Lorraine Hatzikotoulas, Konstantinos Farmaki, Aliki-Eleni Bjornland, Thea Waples, Ryan Appel, Emil V. R. Casalone, Elisabetta Melloni, Giorgio Kilian, Britt Rayner, Nigel W. Ntalla, Ioanna Kundu, Kousik Walter, Klaudia Danesh, John Butterworth, Adam Barroso, Inês Tsafantakis, Emmanouil Dedoussis, George Moltke, Ida Zeggini, Eleftheria |
| author_facet | Gilly, Arthur Suveges, Daniel Kuchenbaecker, Karoline Pollard, Martin Southam, Lorraine Hatzikotoulas, Konstantinos Farmaki, Aliki-Eleni Bjornland, Thea Waples, Ryan Appel, Emil V. R. Casalone, Elisabetta Melloni, Giorgio Kilian, Britt Rayner, Nigel W. Ntalla, Ioanna Kundu, Kousik Walter, Klaudia Danesh, John Butterworth, Adam Barroso, Inês Tsafantakis, Emmanouil Dedoussis, George Moltke, Ida Zeggini, Eleftheria |
| author_sort | Gilly, Arthur |
| collection | PubMed |
| description | The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10(−8); APOC3 and triglyceride levels, P = 1.5 × 10(−26)), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10(−8)), indicating a role for this gene in lipid metabolism. |
| format | Online Article Text |
| id | pubmed-6220258 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-62202582018-11-08 Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits Gilly, Arthur Suveges, Daniel Kuchenbaecker, Karoline Pollard, Martin Southam, Lorraine Hatzikotoulas, Konstantinos Farmaki, Aliki-Eleni Bjornland, Thea Waples, Ryan Appel, Emil V. R. Casalone, Elisabetta Melloni, Giorgio Kilian, Britt Rayner, Nigel W. Ntalla, Ioanna Kundu, Kousik Walter, Klaudia Danesh, John Butterworth, Adam Barroso, Inês Tsafantakis, Emmanouil Dedoussis, George Moltke, Ida Zeggini, Eleftheria Nat Commun Article The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10(−8); APOC3 and triglyceride levels, P = 1.5 × 10(−26)), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10(−8)), indicating a role for this gene in lipid metabolism. Nature Publishing Group UK 2018-11-07 /pmc/articles/PMC6220258/ /pubmed/30405126 http://dx.doi.org/10.1038/s41467-018-07070-8 Text en © The Author(s) 2018 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 Gilly, Arthur Suveges, Daniel Kuchenbaecker, Karoline Pollard, Martin Southam, Lorraine Hatzikotoulas, Konstantinos Farmaki, Aliki-Eleni Bjornland, Thea Waples, Ryan Appel, Emil V. R. Casalone, Elisabetta Melloni, Giorgio Kilian, Britt Rayner, Nigel W. Ntalla, Ioanna Kundu, Kousik Walter, Klaudia Danesh, John Butterworth, Adam Barroso, Inês Tsafantakis, Emmanouil Dedoussis, George Moltke, Ida Zeggini, Eleftheria Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title | Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title_full | Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title_fullStr | Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title_full_unstemmed | Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title_short | Cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| title_sort | cohort-wide deep whole genome sequencing and the allelic architecture of complex traits |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220258/ https://www.ncbi.nlm.nih.gov/pubmed/30405126 http://dx.doi.org/10.1038/s41467-018-07070-8 |
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