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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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