Cardiovascular genetics articles from across Nature Portfolio

This study identifies an altered chromatin conformation associated to a cardiac disorder observed in 7 independent families. A deletion of 2 diverging CTCF binding sites on 4q25 induces TAD fusion and leads to PITX2 expression dysregulation.

Here the authors report 20 novel genomic risk loci for calcific aortic valve stenosis, the most common heart valve disorder. Using RNA sequencing in 500 human aortic valves, they prioritize candidate causal genes including TWIST1, a gene involved in endothelial-mesenchymal transition.

Genome-wide association studies allow connecting genomic information with complex traits. Rodrigo Bonazzola et al. develop a framework consisting of several deep learning tools to improve the discoverability of genes that influence specific geometric features of the heart.

Shetty et al. report that individuals of African ancestry harboring a high-proportion spliced-in titin truncating variant have a similar increase in the risk of atrial fibrillation, dilated cardiomyopathy and heart failure as individuals of European ancestry.

Reduced expression of smooth muscle α-actin (αSMA), a crucial piece of the vascular smooth muscle cell cytoplasmic contractile apparatus, contributes to these cells’ dysfunction in vascular diseases. αSMA is now shown to localize in the nucleus and bind chromatin-remodeling complexes to regulate smooth muscle contractile gene expression.

Liu and colleagues demonstrate the crucial role of IL-6 signalling in the development of atherosclerosis driven by Tet2-related clonal haematopoiesis.

Clonal haematopoiesis of indeterminate potential (CHIP) is defined as an expansion of mutant blood stem cells in individuals without haematological malignancies. CHIP is linked to an increased risk of non-cancerous disorders such as atherosclerotic cardiovascular disease, possibly because mutant innate immune cells have pro-inflammatory phenotypes. Prospective studies are needed to determine whether individuals with CHIP might benefit from anti-inflammatory therapies.

Clonal hematopoiesis of indeterminate potential (CHIP) is a blood disorder that can increase the risk of cardiovascular disease. A new study reveals that CHIP driven by somatic mutations in DNA damage repair genes increases the risk of CVD in humans, and provides mechanistic insights in murine models.

Regulatory elements including promoters and enhancers control tissue- and context-dependent gene expression. A new study presents an atlas of transcribed regulatory elements in human heart compartments, and their changes in transcription in the failing heart.

Rupture or dissection of the aorta is often fatal. Tcheandjieu and colleagues now identify key pathways underlying aortic dilatation, a common prelude to acute aortic events, and assess the utility of a polygenic risk score to identify those at highest risk of aortic death in whom prophylactic surgical repair may be beneficial.