Circulation, Volume 153, Issue 14 , Page 1060-1076, April 7, 2026. BACKGROUND:Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability.
Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV.METHODS:A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed.
Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified in zebrafish.
A polygenic risk score was developed, its association with BAV was evaluated in an independent cohort, and its association with a wide range of phenotypes (n=976) was evaluated in UK Biobank (n=355 618 individuals).RESULTS:Thirty-six genomic loci were identified, including 32 that were not described previously.
Circulation published a clinical update in Cardiology on 06 Feb 2026.
The item focuses on Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve.
Review the original article for the full source wording and details.