Phenome-wide analyses establish a specific association between aortic valve PALMD expression and calcific aortic valve stenosis.
Zhonglin LiNathalie GaudreaultBenoit J ArsenaultPatrick MathieuYohan BosseSébastien ThériaultPublished in: Communications biology (2020)
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.
Keyphrases
- aortic valve
- transcatheter aortic valve replacement
- transcatheter aortic valve implantation
- aortic valve replacement
- poor prognosis
- aortic stenosis
- adipose tissue
- atrial fibrillation
- gene expression
- functional connectivity
- binding protein
- heart failure
- genome wide
- resting state
- long non coding rna
- randomized controlled trial
- left ventricular
- insulin resistance
- pulmonary hypertension
- white matter
- type diabetes
- dna methylation
- single molecule
- venous thromboembolism
- left atrial
- pregnant women
- pregnancy outcomes
- case control
- catheter ablation
- subarachnoid hemorrhage
- oral anticoagulants