| Title: | Phenome-wide analyses establish a specific association between aortic valve PALMD expression and calcific aortic valve stenosis |
| Journal: | Communications Biology |
| Published: | 28 Aug 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32859967/ |
| DOI: | https://doi.org/10.1038/s42003-020-01210-x |
| URL: | https://www.nature.com/articles/s42003-020-01210-x.pdf |
| Citations: | 13 (7 in last 2 years) as of 8 Aug 2024 |
Publication 7634
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Abstract
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.19 Keywords
- Adult
- Aged
- Aortic Valve
- Aortic Valve Stenosis
- Calcinosis
- Female
- Gene Expression Regulation
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Membrane Proteins
- Middle Aged
- Phenomics
- Phenotype
- Quantitative Trait Loci
- Risk Factors
- Stroke
- Transcriptome
6 Authors
- Zhonglin Li
- Nathalie Gaudreault
- Benoit J. Arsenault
- Patrick Mathieu
- Yohan Bossé
- Sébastien Thériault
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