Paradox Between Race and Risk of Atrial Fibrillation Remains Unexplained Interview with:

Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS Director of Clinical Research Division of Cardiology Endowed Professor of Atrial Fibrillation Research University of California, San Francisco

Dr. Gregory Marcus

Gregory M Marcus, MD, MAS, FACC, FAHA, FHRS
Director of Clinical Research
Division of Cardiology
Endowed Professor of Atrial Fibrillation Research
University of California, San Francisco What is the background for this study? What are the main findings?

Response: We and others have previously demonstrated that, despite the observation that African Americans on average exhibit more risk factors for atrial fibrillation, they demonstrate a substantially reduced risk of the disease. This suggests that, if we could understand the mechanism underlying this apparent paradox, we might learn something fundamentally important to atrial fibrillation that would be relevant to treating or preventing the disease regardless of race.

Building on our previous work demonstrating that, among African Americans, more European ancestry (determined by genomic testing) was a statistically significant predictor of atrial fibrillation, we sought to identify the gene(s) that might underlie this observation. The analysis took two forms.

First, we examined if any differences among several well-established single nucleotide polymorphisms (SNP) associated with atrial fibrillation might mediate the race-atrial fibrillation relationship. One such SNP statistically mediated (rs10824026) up to about a third of the race-atrial fibrillation relationship. It’s important to mention that a causal relationship cannot be proven here.

Perhaps more remarkable was the observation that the disease-associated alleles of the SNPs most closely associated with atrial fibrillation in multiple studies were actually significantly more common among African Americans, pointing to the complex nature of both the race-atrial fibrillation relationship as well as the genetics of atrial fibrillation.

Finally, leveraging the ancestral relationships, we performed a genome wide admixture mapping study with the hope of reducing the penalty for multiple hypothesis testing incurred in conventional genome wide association studies. While several loci revealed associations with atrial fibrillation with small p values, none met our criteria for genome wide significance. What should readers take away from your report?
1. Differences in common genetic variants associated with atrial fibrillation do not appear to explain the substantial differences in atrial fibrillation risk among African Americans compared to Whites.

2. While insufficient power may explain the negative results of our genome wide admixture mapping study, it may also be that the substantial difference in atrial fibrillation risk across races is due to either multiple genetic differences, environmental differences, or as yet unrecognized gene-gene and/ or gene-environment interactions. What recommendations do you have for future research as a result of this study?

1. Larger epidemiologic studies with inclusion of large numbers of racial and ethnic minorities and meticulous ascertainment of atrial fibrillation are needed.
2. The paradox related to race and atrial fibrillation remains unexplained, but pursuing this research conundrum is likely a fruitful source of inquiry to reveal mechanisms fundamental to this very important arrhythmia. Thank you for your contribution to the community.


Roberts JD, Hu D, Heckbert SR, et al. Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals. JAMA Cardiol. Published online June 22, 2016. doi:10.1001/jamacardio.2016.1185.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on June 22, 2016 by Marie Benz MD FAAD