The Genes Responsible for Dilated Cardiomyopathy
Six new genetic loci linked to the risk of Dilated Cardiomyopathy (DCM) have been discovered in a new study. The research, published in PLOS One, identified eleven single nucleotide polymorphisms (SNPs) across eight loci, six of which had not previously been linked to the condition.
The study was completed by an international team, led by researchers at the French Institut National de la Santé et de la Recherche Médicale (INSERM, the National Institute of Health and Medical Research). Using array-based exome profiling, the team examined the exome data of 2796 individuals with DCM and 6877 healthy people, from 6 populations with European ancestry. The participants were recruited in the USA, the UK, France, Germany, and Italy.
“We confirmed associations with variants in ZBTB17-HSPB7 and BAG3 and identified six novel loci,” the authors wrote. “Statistical analyses, cardiac tissue expression, and physiology suggest that the most likely causal genes are HSPB7, BAG3, TTN, SLC39A8, MLIP, FLNC, ALPK3, and FHOD3.”
DCM is a condition with strong familial ties that affects heart muscle, causing heart failure and often resulting in sudden death. Prior studies have identified a range of common and rare variants that account for some cases of hereditary DCM, but our understanding of the physiology of the condition is still not very clear.
To try to clarify the links between the genes and the disease, the team performed fine mapping to identify the genes with the most profound effect on DCM. Their results identified potential roles of the genes in heat shock response, muscle, and transport, alongside a variety of other pathways.
This research is step forwards in understanding DCM, but the authors warn that there are likely many more genetic loci that have yet to be identified.
“We also investigated a panel of 48 known cardiomyopathy genes,” they wrote. “Collectively, rare or common variants with elevated in silico severity scores were associated with DCM, indicating that the spectrum of genes contributing to sporadic DCM extends beyond those identified here.”