Decoding the Genetic Complexity of Bicuspid Aortic Valve: From Genome-Wide Discovery to Clinical Risk Stratification

Identification of 36 genomic loci associated with Bicuspid Aortic Valve (BAV), including 32 previously undescribed loci, significantly expanding the known genetic landscape of the disease.
Transcriptome-wide prioritization identified KANK2, ERBB4, PRDM6, and STRN as key causal candidates, with KANK2 and ERBB4 validated through human aortic valve expression data.
Functional validation in zebrafish models confirmed that disruption of WNT4, LEF1, STRN, and KANK2 leads to significant defects in cardiac development.
A novel Polygenic Risk Score (PRS) demonstrates a twofold increase in BAV risk per standard deviation and reveals a robust genetic correlation with thoracic aortic aneurysm and atrial fibrillation.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Identification of 36 genomic loci associated with Bicuspid Aortic Valve (BAV), including 32 previously undescribed loci, significantly expanding the known genetic landscape of the disease.
Transcriptome-wide prioritization identified KANK2, ERBB4, PRDM6, and STRN as key causal candidates, with KANK2 and ERBB4 validated through human aortic valve expression data.
Functional validation in zebrafish models confirmed that disruption of WNT4, LEF1, STRN, and KANK2 leads to significant defects in cardiac development.
A novel Polygenic Risk Score (PRS) demonstrates a twofold increase in BAV risk per standard deviation and reveals a robust genetic correlation with thoracic aortic aneurysm and atrial fibrillation.

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