Phenome-wide analyses establish a specific association between aortic valve PALMD expression and calcific aortic valve stenosis.
Adult
Aged
Aortic Valve
/ pathology
Aortic Valve Stenosis
/ genetics
Calcinosis
/ genetics
Female
Gene Expression Regulation
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Male
Membrane Proteins
/ genetics
Middle Aged
Phenomics
Phenotype
Quantitative Trait Loci
/ genetics
Risk Factors
Stroke
/ genetics
Transcriptome
/ genetics
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
28 08 2020
28 08 2020
Historique:
received:
06
03
2020
accepted:
04
08
2020
entrez:
30
8
2020
pubmed:
30
8
2020
medline:
17
6
2021
Statut:
epublish
Résumé
Calcific aortic valve stenosis (CAVS) is a frequent heart disease with significant morbidity and mortality. Recent genomic studies have identified a locus near the gene PALMD (palmdelphin) strongly associated with CAVS. Here, we show that genetically-determined expression of PALMD in the aortic valve is inversely associated with CAVS, with a stronger effect in women, in a meta-analysis of two large cohorts totaling 2359 cases and 350,060 controls. We further demonstrate the specificity of this relationship by showing the absence of other significant association between the genetically-determined expression of PALMD in 9 tissues and 852 phenotypes. Using genome-wide association studies meta-analyses of cardiovascular traits, we identify a significant colocalized positive association between genetically-determined expression of PALMD in four non-cardiac tissues (brain anterior cingulate cortex, esophagus muscularis, tibial nerve and subcutaneous adipose tissue) and atrial fibrillation. The present work further establishes PALMD as a promising molecular target for CAVS.
Identifiants
pubmed: 32859967
doi: 10.1038/s42003-020-01210-x
pii: 10.1038/s42003-020-01210-x
pmc: PMC7455695
doi:
Substances chimiques
Membrane Proteins
0
PALMD protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
477Subventions
Organisme : CIHR
ID : PJT - 162344
Pays : Canada
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