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Nat Commun. 2018 Mar 7;9(1):988. doi: 10.1038/s41467-018-03260-6.

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

Author information

1
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Quebec City, QC, G1V 4G5, Canada.
2
Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, QC, G1V 0A6, Canada.
3
Cardiology Department, AP-HP, Bichat Hospital, 75018, Paris, France.
4
INSERM U698 and University Paris 7, 75018, Paris, France.
5
Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Quebec City, QC, G1V 4G5, Canada. yohan.bosse@criucpq.ulaval.ca.
6
Department of Molecular Medicine, Laval University, Quebec City, QC, G1V 0A6, Canada. yohan.bosse@criucpq.ulaval.ca.

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.

PMID:
29511167
PMCID:
PMC5840407
DOI:
10.1038/s41467-018-03260-6
[Indexed for MEDLINE]
Free PMC Article

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