New research from University College London (UCL), Imperial College London, and the MRC Laboratory of Medical Sciences has revealed that dilated cardiomyopathy (DCM), a serious heart condition, is influenced by the cumulative effects of thousands of genetic variations, rather than being solely caused by a single faulty gene.
Published in Nature Genetics, the study marks a significant shift in understanding the genetic underpinnings of DCM, a condition that affects up to 260,000 people in the UK and is the leading cause of heart transplants. The findings provide a framework for better risk assessment and pave the way for more personalized treatment strategies.
DCM occurs when the heart becomes enlarged and weakened, impairing its ability to pump blood efficiently. While the condition is often linked to single-gene mutations passed through families, the study reveals that about 25-33% of DCM risk is driven by thousands of small genetic differences dispersed throughout the genome.
The research team analyzed data from 16 studies and new datasets, comparing the genomes of 14,256 people with DCM to over a million individuals without the condition. This large-scale analysis identified 80 regions of the genome linked to DCM and 62 specific genes likely associated with the disease.
One of the study’s key breakthroughs is the development of a polygenic risk score, which combines the effects of many genetic variations to assess an individual’s likelihood of developing DCM.
The team tested the risk score on a dataset from the UK Biobank involving 347,585 participants. Results showed that individuals with a rare disease-causing variant and a high polygenic risk score (top 20%) were four times more likely to develop DCM compared to those with low scores.
“This finding provides a new way to predict disease risk more precisely, especially for patients and families where cardiomyopathy runs in the family,” said Dr. Tom Lumbers, co-lead author and UCL Institute of Health Informatics researcher. “By identifying those at highest risk, clinicians can offer closer monitoring and early participation in preventive trials.”The study not only offers new insights into the genetic complexity of DCM but also opens doors for enhancing clinical genetic testing.
Professor James Ware of Imperial College London explained, “Our findings increase the number of patients who can receive a genetic explanation for their condition. It also allows us to identify high-risk individuals who could benefit from more personalized care.”Moreover, the identified genes shed light on biological pathways associated with DCM, offering potential targets for future treatments.
As reported by medicalxpress, the findings have been welcomed by experts, including Professor Metin Avkiran of the British Heart Foundation, who said, “This study provides a clearer picture of individual risk for those without a known single-gene mutation. These insights could lead to more personalized care and reveal potential treatment targets.”
Researchers aim to further integrate polygenic risk scores into genetic testing, improving risk prediction and offering more people a genetic explanation for DCM.This breakthrough not only advances the understanding of DCM but also represents a significant step toward precision medicine for a condition that has few treatment options once it progresses.