Synergistic interaction between risk burden and genetics for atrial fibrillation development

1. In a large prospective study, risk burden and genetic predisposition acted synergistically to significantly increase the risk of developing atrial fibrillation. 

Evidence Rating Level: 2 (Good)

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and is associated with a high risk of thromboembolism and death. This study aims to identify the effects of both risk factor burden and genetic predisposition on the 10-year risk of developing atrial fibrillation. 352,804 participants aged 40-69 were enrolled in this study between 2006 and 2010 from the UK biobank. A polygenic risk score was calculated for each participant, using 165 known genetic risk markers for atrial fibrillation. Risk factor burden was determined by BMI, diabetes mellitus, alcohol use, smoking, blood pressure, and cardiac history (MI or CHF). Participants were divided into three age groups: 40-49, 50-59, and 60-69. A lower risk factor burden was significantly associated with a later onset of atrial fibrillation (p<0.001). In each age category, risk factor burden and genetic predisposition acted synergistically to significantly increase the AF risk (p <0.05). The greatest AF risk was found for those aged 60-69 with elevated risk factor profile and genetic predisposition (10-year risk 11.1%, 95% CI 10.72-11.49). In comparison, participants aged 60-69 with an elevated risk factor burden and low genetic predisposition had a 3.91% 10-year risk of developing AF (95% CI 3.68-4.14). Overall, this study demonstrates that risk burden and genetic predisposition act synergistically to increase the risk of developing AF. In the clinical setting, identifying younger individuals with a strong genetic predisposition for AF may be a beneficial preventative strategy, providing the opportunity for early intervention to reduce risk factor profile and 10-year AF risk.

Click to read the study in BMC Medicine

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