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

Sébastien Thériault, Nathalie Gaudreault, Maxime Lamontagne, David Messika-Zeitoun, Marie-Annick Clavel, Romain Capoulade, François Dagenais, Philippe Pibarot, Patrick Mathieu, Yohan Bossé

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Received: 14th November 17

Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease with no drug that can stop or delay its progression. A GWAS on 1,009 cases and 1,017 ethnically-matched controls was combined with the first large-scale eQTL mapping study of human aortic valve tissues (n=233) to identify susceptibility genes for CAVS. Replication was performed in UK Biobank including 1,391 cases and 352,195 controls. Transcriptome-wide association study (TWAS) revealed PALMD(palmdelphin) as significantly associated with CAVS. The CAVS risk alleles and increasing disease severity were both associated with lowered mRNA expression levels of PALMD in valve tissues. The top variant identified showed similar effect and strong association with CAVS (P=1.53x10-10) in UK Biobank. The identification of PALMD as a susceptibility gene for CAVS provides new insights about the genetic nature of this disease and opens new avenues to investigate its etiology and develop much-needed therapeutic options.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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