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Journal articles
Multitrait GWAS to connect disease variants and biological mechanisms
Hanna Julienne
1, *
Vincent Laville
1
Zachary Mccaw
2
Zihuai He
3, 4
Vincent Guillemot
1
Carla Lasry
1
Andrey Ziyatdinov
2
Cyril Nerin
1
Amaury Vaysse
1
Pierre Lechat
1
Hervé Ménager
1
Wilfried Le Goff
5
Marie-Pierre Dube
6
Peter Kraft
2
Iuliana Ionita-Laza
7
Bjarni Vilhjálmsson
8
Hugues Aschard
1, *
*
Corresponding author
Hanna Julienne 1
Correspondent author IdHAL : hanna-julienne ORCID : https://orcid.org/0000-0001-8214-9412
Vincent Laville 1
Author
Zachary Mccaw 2
Author ORCID : https://orcid.org/0000-0002-2006-9828
Zihuai He 3, 4
Author ORCID : https://orcid.org/0000-0002-8220-4183
Vincent Guillemot 1
Author ORCID : https://orcid.org/0000-0002-7421-0655
Carla Lasry 1
Author
Andrey Ziyatdinov 2
Author
Cyril Nerin 1
Author
Amaury Vaysse 1
Author IdHAL : avaysse ORCID : https://orcid.org/0000-0003-2397-4230
Pierre Lechat 1
Author ORCID : https://orcid.org/0000-0003-1050-5582
Hervé Ménager 1
Author IdHAL : herve-menager ORCID : https://orcid.org/0000-0002-7552-1009
Wilfried Le Goff 5
Author
Marie-Pierre Dube 6
Author ORCID : https://orcid.org/0000-0001-8442-4393
Peter Kraft 2
Author ORCID : https://orcid.org/0000-0002-4472-8103
Iuliana Ionita-Laza 7
Author
Bjarni Vilhjálmsson 8
Author ORCID : https://orcid.org/0000-0003-2277-9249
Hugues Aschard 1
Correspondent author ORCID : https://orcid.org/0000-0002-7554-6783
1
Département de Biologie Computationnelle - Department of Computational Biology (25-28 rue du Docteur Roux, 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- CNRS - Centre National de la Recherche Scientifique : USR 3756 (France)
2
Harvard T.H. Chan School of Public Health ( 677 Huntington Avenue, Boston, MA 02115 - United States)
3
Stanford University School of Medicine [CA, USA] (291 Campus Drive, Stanford, CA 94305. - United States)
4
Stanford University (450 Serra Mall, Stanford, CA 94305-2004 - United States)
5
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN] (Faculté de Médecine - 91 boulevard de l'Hôpital 75634 Paris Cedex 13 - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1166 (101, rue de Tolbiac, 75013 Paris - France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
- IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (Hôpital la Pitié Salpêtrière
47-83 boulevard de l’Hôpital
75013 Paris 13 - France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
- AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) (France)
- SU - Sorbonne Université (21 rue de l’École de médecine - 75006 Paris - France)
- CHU Pitié-Salpêtrière [AP-HP] (47-83 Boulevard de l'Hôpital, 75013 Paris - France)
6
Montreal Heart Institute - Institut de Cardiologie de Montréal (5000 Rue Bélanger, Montréal, QC H1T 1C8, Canada - Canada)
7
Columbia University [New York] (Columbia University in the City of New York, 2960 Broadway, New York, NY 10027-6902 - United States)
8
Aarhus University [Aarhus] (Nordre Ringgade 1 DK-8000 Aarhus C - Denmark)
Abstract : 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.
Document type :
Journal articles
Complete list of metadata
https://hal-pasteur.archives-ouvertes.fr/pasteur-03526210
Contributor : Hugues Aschard Connect in order to contact the contributor
Submitted on : Friday, January 14, 2022 - 12:31:52 PM
Last modification on : Tuesday, January 18, 2022 - 2:46:04 PM
Contributor : Hugues Aschard Connect in order to contact the contributor
Submitted on : Friday, January 14, 2022 - 12:31:52 PM
Last modification on : Tuesday, January 18, 2022 - 2:46:04 PM
Licence
Distributed under a Creative Commons Attribution 4.0 International License
Identifiers
- HAL Id : pasteur-03526210, version 1
- DOI : 10.1371/journal.pgen.1009713
- PUBMED : 34460823
- PUBMEDCENTRAL : PMC8437297
Collections
PASTEUR | ICAN | SORBONNE-UNIVERSITE | SU-MEDECINE | SU-TI | ANR | CNRS | INSERM
Citation
Hanna Julienne, Vincent Laville, Zachary Mccaw, Zihuai He, Vincent Guillemot, et al.. Multitrait GWAS to connect disease variants and biological mechanisms. PLoS Genetics, Public Library of Science, 2021, 17 (8), pp.e1009713. ⟨10.1371/journal.pgen.1009713⟩. ⟨pasteur-03526210⟩
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