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Multitrait GWAS to connect disease variants and biological mechanisms
Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Ou...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437297/ https://www.ncbi.nlm.nih.gov/pubmed/34460823 http://dx.doi.org/10.1371/journal.pgen.1009713 |
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author | Julienne, Hanna Laville, Vincent McCaw, Zachary R. He, Zihuai Guillemot, Vincent Lasry, Carla Ziyatdinov, Andrey Nerin, Cyril Vaysse, Amaury Lechat, Pierre Ménager, Hervé Le Goff, Wilfried Dube, Marie-Pierre Kraft, Peter Ionita-Laza, Iuliana Vilhjálmsson, Bjarni J. Aschard, Hugues |
author_facet | Julienne, Hanna Laville, Vincent McCaw, Zachary R. He, Zihuai Guillemot, Vincent Lasry, Carla Ziyatdinov, Andrey Nerin, Cyril Vaysse, Amaury Lechat, Pierre Ménager, Hervé Le Goff, Wilfried Dube, Marie-Pierre Kraft, Peter Ionita-Laza, Iuliana Vilhjálmsson, Bjarni J. Aschard, Hugues |
author_sort | Julienne, Hanna |
collection | PubMed |
description | Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Our framework incorporates multitrait association mapping along with an investigation of the breakdown of genetic associations into clusters of variants harboring similar multitrait association profiles. Focusing on two subsets of immunity and metabolism phenotypes, we then demonstrate how genetic variants within clusters can be mapped to biological pathways and disease mechanisms. Finally, for the metabolism set, we investigate the link between gene cluster assignment and the success of drug targets in randomized controlled trials. |
format | Online Article Text |
id | pubmed-8437297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84372972021-09-14 Multitrait GWAS to connect disease variants and biological mechanisms Julienne, Hanna Laville, Vincent McCaw, Zachary R. He, Zihuai Guillemot, Vincent Lasry, Carla Ziyatdinov, Andrey Nerin, Cyril Vaysse, Amaury Lechat, Pierre Ménager, Hervé Le Goff, Wilfried Dube, Marie-Pierre Kraft, Peter Ionita-Laza, Iuliana Vilhjálmsson, Bjarni J. Aschard, Hugues PLoS Genet Research Article Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Our framework incorporates multitrait association mapping along with an investigation of the breakdown of genetic associations into clusters of variants harboring similar multitrait association profiles. Focusing on two subsets of immunity and metabolism phenotypes, we then demonstrate how genetic variants within clusters can be mapped to biological pathways and disease mechanisms. Finally, for the metabolism set, we investigate the link between gene cluster assignment and the success of drug targets in randomized controlled trials. Public Library of Science 2021-08-30 /pmc/articles/PMC8437297/ /pubmed/34460823 http://dx.doi.org/10.1371/journal.pgen.1009713 Text en © 2021 Julienne et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Julienne, Hanna Laville, Vincent McCaw, Zachary R. He, Zihuai Guillemot, Vincent Lasry, Carla Ziyatdinov, Andrey Nerin, Cyril Vaysse, Amaury Lechat, Pierre Ménager, Hervé Le Goff, Wilfried Dube, Marie-Pierre Kraft, Peter Ionita-Laza, Iuliana Vilhjálmsson, Bjarni J. Aschard, Hugues Multitrait GWAS to connect disease variants and biological mechanisms |
title | Multitrait GWAS to connect disease variants and biological mechanisms |
title_full | Multitrait GWAS to connect disease variants and biological mechanisms |
title_fullStr | Multitrait GWAS to connect disease variants and biological mechanisms |
title_full_unstemmed | Multitrait GWAS to connect disease variants and biological mechanisms |
title_short | Multitrait GWAS to connect disease variants and biological mechanisms |
title_sort | multitrait gwas to connect disease variants and biological mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437297/ https://www.ncbi.nlm.nih.gov/pubmed/34460823 http://dx.doi.org/10.1371/journal.pgen.1009713 |
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