1. Genetic Association Analyses Highlight
- Author
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Sébastien, Thériault, Christian, Dina, David, Messika-Zeitoun, Solena, Le Scouarnec, Romain, Capoulade, Nathalie, Gaudreault, Sidwell, Rigade, Zhonglin, Li, Floriane, Simonet, Maxime, Lamontagne, Marie-Annick, Clavel, Benoit J, Arsenault, Anne-Sophie, Boureau, Simon, Lecointe, Estelle, Baron, Stéphanie, Bonnaud, Matilde, Karakachoff, Eric, Charpentier, Imen, Fellah, Jean-Christian, Roussel, Jean, Philippe Verhoye, Christophe, Baufreton, Vincent, Probst, Ronan, Roussel, Richard, Redon, François, Dagenais, Philippe, Pibarot, Patrick, Mathieu, Thierry, Le Tourneau, Yohan, Bossé, and Jean-Jacques, Schott
- Subjects
Cohort Studies ,Interleukin-6 ,Aortic Valve ,Calcinosis ,Humans ,Genetic Predisposition to Disease ,Aortic Valve Stenosis ,Alkaline Phosphatase ,Microtubule-Associated Proteins ,Polymorphism, Single Nucleotide ,Genome-Wide Association Study - Abstract
Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes,A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits.In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci:Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.
- Published
- 2020