Heart failure hits Black communities harder – but now we know why a single gene might be the culprit. Imagine discovering that a tiny change in your DNA could double your chances of developing a serious heart condition, yet this revelation has been hiding in plain sight, especially affecting people of African descent. It's a stark reality that's spurred groundbreaking research, and trust me, the implications are nothing short of mind-blowing.
Dilated cardiomyopathy, or DCM for short, is a major player in heart failure cases. This condition weakens the heart's pumping ability, leading to fatigue, shortness of breath, and potentially life-threatening complications. Alarmingly, it's about twice as prevalent in Black individuals compared to white individuals. And get this: traditional risk factors like high blood pressure or even barriers to accessing quality healthcare don't fully account for this disparity. But here's where it gets controversial – what if genetics, long overlooked in diverse populations, holds the key to explaining this inequality?
Enter a team of researchers from Mass General Brigham, the Broad Institute of MIT and Harvard, and VA Boston. By tapping into massive, genetically diverse databases, they've pinpointed a common gene variant that significantly ramps up DCM risk. Published in Nature Genetics, their findings reveal that in people of African ancestry, this one genetic tweak could be just as influential for DCM as high blood pressure itself. It's a discovery that challenges the status quo, suggesting biology plays a bigger role than we thought – and this is the part most people miss, because it opens doors to personalized medicine that could level the playing field.
Krishna G. Aragam, MD, MS, the senior and corresponding author, puts it bluntly: 'We've known for ages that people who identify as Black, likely due to their African genetic roots, face a much higher DCM risk that clinical or societal issues alone can't explain. The causes have been mysterious, but thanks to expanding diverse biobanks, we've found a key genetic factor.' Aragam, who was a cardiologist at Mass General Brigham and a scientist at the Broad Institute during this work, now leads Cardiovascular Genomics at the Cleveland Clinic.
The study drew from genetic data of over 95,000 participants with African ancestry in the VA Million Veteran Program (MVP), including almost 2,000 with DCM. Using a genome-wide association study – think of it as a detective tool scanning DNA for subtle differences between those with and without the condition – they uncovered that a single-letter alteration in the CD36 gene boosts DCM risk by 33%. For those unlucky enough to get faulty copies from both parents, the odds shoot up nearly threefold. To clarify for beginners, genes are like instruction manuals in our cells; a variant is just a small spelling mistake that can change how the body functions.
CD36 produces a protein that shuttles fatty acids into heart muscle cells, providing essential energy for the heart to beat strongly. This particular variant appears in 17% of African ancestry individuals but in fewer than 0.1% of European ancestry ones. Researchers speculate it might tie into historical advantages, like resistance to malaria, which could explain its prevalence in certain populations. But here's the controversial twist: does this mean we're overlooking genetic legacies in healthcare, potentially leading to biased treatments? It's a debate worth exploring.
J. Michael Gaziano, MD, MPH, the founding principal investigator of MVP and a co-author, emphasizes the program's purpose: 'MVP was created to include veterans from all walks of life, allowing us to spot genetic disease drivers that might otherwise slip through the cracks. It's astounding that such a widespread and powerful variant stayed hidden so long – and rewarding to witness MVP bridging that knowledge gap.'
They backed up their findings in over 11,000 African ancestry participants from the Penn Medicine Biobank. In additional groups with heart scans, carriers of the CD36 variant showed early signs of weakened heart performance, even without overt symptoms. Altogether, this gene variant might explain roughly 20% of the extra DCM risk in Black patients versus white ones – a figure that could spark discussions on equity in medical research.
Lab tests added weight to the theory: by silencing CD36 in heart cells using RNA interference (a method to temporarily turn off genes), the cells absorbed less fuel and contracted poorly. Patrick T. Ellinor, MD, PhD, co-senior author and executive director of the Mass General Brigham Heart and Vascular Institute, calls it 'fascinating.' 'The CD36 variant links a everyday genetic change to core heart energy questions,' he says. 'It's a prime example of genetics revealing disease mechanisms.'
Looking ahead, the team is comparing CD36 to other DCM genes and investigating if therapies targeting this pathway could restore heart energy balance. Aragam advocates for its inclusion in genetic tests for cardiomyopathy, given its reach in African ancestry groups. 'Its role in heart fueling makes it an exciting avenue for new treatments,' he notes. But this raises provocative questions: Should genetic testing become standard to address disparities, or might it inadvertently deepen divides? And what about the ethical side – using ancestral genetics for modern health?
What do you think? Does this study change how we view heart disease risks, or is there more to uncover? Share your thoughts in the comments – do you agree this warrants widespread genetic screening, or disagree that it's the full story? Let's discuss!
Reference: Huffman JE, Gaziano L, Al Sayed ZR, et al. An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy. Nat Genet. 2025. doi:10.1038/s41588-025-02372-2 (https://doi.org/10.1038/s41588-025-02372-2)
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