• Common genetic variants significantly impact heart failure risk, potentially exceeding the impact of rare variants.
• The study identified 176 new genetic variants associated with heart failure through a meta-analysis of over two million individuals.
• Identifying common genetic variants can improve patient risk stratification and potentially lead to new therapies by understanding shared pathways between heart failure and other diseases.

A recent study published in Nature Genetics, led by researchers at Northwestern University Feinberg School of Medicine and the Perelman School of Medicine at the University of Pennsylvania, reveals the significant impact of common genetic variants on heart failure risk. The study involved a meta-analysis of genome-wide association studies, including genetic data from over 207,000 individuals with heart failure and more than two million without. The findings challenge the traditional focus on rare genetic variants and highlight the importance of considering common variants for improved risk assessment and potential therapeutic interventions.

• What: A study identifying the significant contribution of common genetic variants to heart failure risk, revealing 176 new associated variants.
• Who: David Lee, MD, PhD (lead author), Megan Roy-Puckelwartz, PhD, Elizabeth McNally, MD, PhD (co-authors), investigators at Northwestern University Feinberg School of Medicine and the Perelman School of Medicine at the University of Pennsylvania.
• When: Study recently published in Nature Genetics.
• Where: Research conducted at Northwestern University Feinberg School of Medicine and the Perelman School of Medicine at the University of Pennsylvania.

The study's findings represent a significant shift in understanding heart failure risk assessment. By demonstrating the substantial role of common genetic variants, the research suggests a more comprehensive approach to patient stratification. This could lead to earlier identification of individuals at risk, even in the absence of rare genetic variants traditionally associated with the condition. Furthermore, the identification of shared pathways between heart failure and other diseases, such as diabetes, opens avenues for developing targeted therapies that address the underlying biological processes.

Much of the focus, at least on the clinical side, has been looking at rare genetic variants and testing for them and determining your heart failure risk. But based on our results, the common genetic variants in your genome can contribute just as much, if not more than, rare genetic variants to your heart failure risk.

If you consider an individual’s common variant genetic background, we can identify individuals who are also at high risk for acquiring heart failure, even if they don’t have these rare genetic variants that typically are associated with high penetrance and causing disease. Our study shows that even for individuals who are carriers of these rare genetic variants, their common variant background can modify their risks.

Because we were able to identify so many common genetic variants that contribute to heart failure risk, we could cluster those and look across different diseases and find shared pathways between these diseases and heart failure to better understand the fundamental biological processes that are dysregulated in heart failure.

The study published in Nature Genetics underscores the importance of considering common genetic variants in addition to rare variants when assessing heart failure risk. This comprehensive approach has the potential to improve patient risk stratification, identify shared disease pathways, and ultimately inform the development of more effective therapies. Future research will likely focus on further elucidating the specific mechanisms by which these common variants contribute to heart failure and translating these findings into clinical applications.