Titre :

Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

Auteur(s) :

Yu, Mengyao [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Kyryachenko, Sergiy [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Debette, Stephanie [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Bordeaux population health [BPH]
Amouyel, Philippe [Auteur]
Excellence Laboratory LabEx DISTALZ
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Schott, Jean-Jacques [Auteur]
ITX - unité de recherche de l'institut du thorax [ITX]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Le Tourneau, Thierry [Auteur]
ITX - unité de recherche de l'institut du thorax [ITX]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Dina, Christian [Auteur]
ITX - unité de recherche de l'institut du thorax [ITX]
Centre Hospitalier Universitaire de Nantes = Nantes University Hospital [CHU Nantes]
Norris, Russell [Auteur]
Medical University of South Carolina [Charleston] [MUSC]
Hagège, Albert [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Jeunemaitre, Xavier [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]
Bouatia-Naji, Nabila [Auteur]
Paris-Centre de Recherche Cardiovasculaire [PARCC (UMR_S 970/ U970)]

Titre de la revue :

Circulation: Genomic and Precision Medicine

Éditeur :

American Heart Association

Date de publication :

2021-10

Mot(s)-clé(s) en anglais :

association
computational biology
heart valve diseases
meta-analysis
mitral valve prolapse

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study has identified 6 risk loci for MVP. But these loci explained ...
Lire la suite >Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study has identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. Methods: We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used Functional Mapping and Annotation of Genome-Wide Association Studies for post-genome-wide association study annotations and Multi-marker Analysis of GenoMic Annotation for gene-based and gene-set analyses. Results: We found Trans-Omics for Precision Medicine imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1 . We identified an additional risk locus on Chr1 ( SYT2 ) and 2 suggestive risk loci on chr8 ( MSRA ) and chr19 ( FBXO46 ), all driven by common variants. Gene-based association using Multi-marker Analysis of GenoMic Annotation revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. Conclusions: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.Lire moins >

Langue :

Anglais

Comité de lecture :

Oui

Audience :

Internationale

Vulgarisation :

Non

Projet ANR :

Prolapsus Valvulaire Mitral: De la génétique à l'amélioration de la prise en charge du patient

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL