Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 65,690 bioRxiv papers from 290,986 authors.

Calcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease with no drug that can stop or delay its progression. Elucidating the genetic factors underpinning CAVS is an urgent priority to find new therapeutic targets. Major landmarks in genetics of CAVS include the discoveries of NOTCH1 and LPA. However, genetic variants in these genes accounted for a small number of cases and low population-attributable risk. Here we mapped a new susceptibility locus for CAVS on chromosome 1p21.2 and identified PALMD (palmdelphin) as the causal gene. PALMD was revealed using a transcriptome-wide association study (TWAS), which combines a genome-wide association study (GWAS) of 1,009 cases and 1,017 ethnically-matched controls with the first large-scale expression quantitative trait loci (eQTL) mapping study on human aortic valve tissues (n=233). The CAVS risk alleles and increasing disease severity were both associated with lowered mRNA expression levels of PALMD in valve tissues. The top variant explained up to 12.5% of the population-attributable risk and showed similar effect and strong association with CAVS (P=1.53x10-10) in UK Biobank comparing 1,391 cases and 352,195 controls. 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.

Download data

• Downloaded 338 times
• Download rankings, all-time:
  • Site-wide: 31,436 out of 65,724
  • In genomics: 3,079 out of 4,480
• Year to date:
  • Site-wide: 53,471 out of 65,724
• Since beginning of last month:
  • Site-wide: 49,746 out of 65,724

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide