A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 29511167.
- Also identified by DOI 10.1038/s41467-018-03260-6 and PMC identifier 5840407.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-10</sup>) 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.
Medical subject headings
- Aortic Valve
- Aortic Valve Stenosis
- Calcinosis
- Membrane Proteins
- Transcriptome