A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis

Sébastien Thériault, Nathalie Gaudreault, Maxime Lamontagne, Mickael Rosa, Marie-Chloé Boulanger, David Messika-Zeitoun, Marie-Annick Clavel, Romain Capoulade, François Dagenais, Philippe Pibarot, Patrick Mathieu and Yohan Bossé ()
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Sébastien Thériault: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Nathalie Gaudreault: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Maxime Lamontagne: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Mickael Rosa: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Marie-Chloé Boulanger: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
David Messika-Zeitoun: Bichat Hospital
Marie-Annick Clavel: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Romain Capoulade: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
François Dagenais: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Philippe Pibarot: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Patrick Mathieu: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval
Yohan Bossé: Institut universitaire de cardiologie et de pneumologie de Québec—Université Laval

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease and the current treatment options cannot stop or delay its progression. A GWAS on 1009 cases and 1017 ethnically matched controls was combined with a large-scale eQTL mapping study of human aortic valve tissues (n = 233) to identify susceptibility genes for CAVS. Replication was performed in the UK Biobank, including 1391 cases and 352,195 controls. A transcriptome-wide association study (TWAS) reveals PALMD (palmdelphin) as significantly associated with CAVS. The CAVS risk alleles and increasing disease severity are both associated with decreased mRNA expression levels of PALMD in valve tissues. The top variant identified shows a similar effect and strong association with CAVS (P = 1.53 × 10−10) in UK Biobank. The identification of PALMD as a susceptibility gene for CAVS provides insights into the genetic nature of this disease, opens avenues to investigate its etiology and to develop much-needed therapeutic options.

Date: 2018
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DOI: 10.1038/s41467-018-03260-6

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