A groundbreaking study led by researchers at University College London (UCL), Imperial College London, and the MRC Laboratory of Medical Sciences has revealed that dilated cardiomyopathy (DCM) may be driven by the combined influence of thousands of genetic variations rather than a single faulty gene as previously believed. The findings, published in Nature Genetics, significantly reshape the understanding of this potentially life-altering heart condition.
DCM is a progressive disease that affects approximately 260,000 people in the UK—about one in every 250 individuals—and is the leading cause of heart transplants. While it was long thought that DCM was primarily caused by a single defective gene passed through families, more than half of affected individuals lack an identifiable gene mutation.
The research demonstrated that around 25–33% of DCM risk stems from the cumulative effects of thousands of genetic variations across the genome. Researchers developed a polygenic risk score to assess a person’s likelihood of developing the condition based on these small genetic effects. Those in the top 1% of genetic risk scores were found to have a fourfold increased risk compared to individuals with an average score.
The study provides new insights into why some individuals with a faulty gene develop DCM while others do not, highlighting the significant role of these cumulative genetic effects. These findings could enable clinicians to better predict patient and family disease risk. Instead of attributing DCM to a single genetic mutation, this new research shows the condition is more akin to common diseases like coronary artery disease, where many genetic differences collectively influence risk.
By analysing data from 16 previous studies and new research with over 14,000 DCM patients and more than a million controls, the team identified 80 genomic regions associated with DCM, most previously unknown and 62 specific genes likely linked to the disease.
The polygenic risk score was further validated using data from 347,585 individuals in the UK Biobank. Among participants with a rare disease-causing variant, those in the top 20% of polygenic risk scores were four times more likely to develop DCM than those in the bottom 20%.
The study authors believe that these findings will improve the precision of clinical genetic testing, offering more patients a genetic explanation for their disease.
The research marks a step toward integrating polygenic risk scores into clinical practice, paving the way for personalised monitoring and preventive strategies. The newly identified genes also provide potential targets for future treatments.
The study sheds light on the complex genetic landscape of DCM, offering hope for improved diagnostics, risk prediction, and therapeutic interventions for this debilitating condition.
Source: University College London
Image Credit: iStock
