Key result
High AF polygenic risk score is linked to ~82% greater risk of sick sinus syndrome.
Why the study?
Does an atrial fibrillation polygenic risk score predict the incidence of sick sinus syndrome in individuals without prior AF or valvular disease?
Cohort (n=405,869)
Yes
Does an atrial fibrillation polygenic risk score predict the incidence of sick sinus syndrome in individuals without prior AF or valvular disease?
Answers are grounded in this paper and cite their sources.
An atrial fibrillation polygenic risk score and elevated cystatin C are independently associated with an increased incidence of sick sinus syndrome, modestly improving risk prediction beyond clinical factors.
BACKGROUND: Sinoatrial node dysfunction and atrial fibrillation (AF) often coexist, and each potentially initiates or perpetuates the other. Consequently, genetic risk factors for AF may be associated with sick sinus syndrome (SSS). This study evaluated clinical, sociodemographic, laboratory and genetic factors in predicting the SSS incidence by using a polygenic risk score (PRS) for AF, given the absence of a dedicated PRS for SSS. METHODS: A total of 502 421 individuals aged 38-73 years across 22 centres from 2006 to 2010 were enrolled in the UK Biobank. After those with incomplete data, prior AF or valvular disease were excluded, 405 869 participants (median age 58.0 (IQR, 50.0-64.0) years; 213 684 (45.2%) male) were analysed. AF PRS categorised the participants into low (first quintile), intermediate (middle three quintiles) and high (fifth quintile) risks. SSS incidence was recorded, and associations were evaluated using Cox regression with sociodemographic, clinical, laboratory and genetic variables. RESULTS: During the median follow-up of 11.9 years, 769 SSS events occurred. Their incidence increased with age (HR 1.52, 95% CI 1.43 to 1.62 per 5 years), male sex (HR 1.39, 95% CI 1.03 to 1.88), prior myocardial infarction (HR 1.54, 95% CI 1.08 to 2.21) and hypertension (HR 1.21, 95% CI 1.02 to 1.42). The high-PRS and intermediate-PRS groups were related to 82% (HR 1.82, 95% CI 1.45 to 2.29) and 32% (HR 1.32, 95% CI 1.07 to 1.62) higher SSS risks, respectively. Cystatin C (HR 1.71, 95% CI 1.33 to 2.22) was also associated with the increased risk. The model's C-index was 0.752 with sociodemographic and clinical variables, but it increased to 0.760 with genetic and biomarker data. CONCLUSION: In addition to sociodemographic and clinical risk factors, AF PRS and cystatin C were linked to the SSS incidence. Although their inclusion modestly improved prediction, these findings highlighted the potential of integrating genetic and biomarker information for comprehensive SSS risk assessments.
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Kim et al. (2026) conducted a cohort in Sick sinus syndrome (n=405,869). High polygenic risk score for atrial fibrillation vs. Low polygenic risk score was evaluated on Sick sinus syndrome incidence (HR 1.82, 95% CI 1.45-2.29). A high polygenic risk score for atrial fibrillation was associated with an 82% higher risk of incident sick sinus syndrome compared to a low risk score (HR 1.82; 95% CI 1.45-2.29).
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