Polygenic risk score for Atrial Fibrillation as a predictor for the incidence of Sick Sinus Syndrome: A comprehensive analysis from the UK biobank

Abstract

Abstract Background Sick sinus syndrome (SSS) and atrial fibrillation (AF) often coexist, demonstrating a bidirectional relationship. The polygenic risk score (PRS) represents the cumulative risk of disease onset based on variations at multiple genetic loci and is known as a predictor for disease incidence. However, the PRS for SSS remains under-investigated. This study aims to evaluate whether the PRS for AF can predict the incidence of SSS in the general population. Methods The UK biobank, comprising of about 500,000 participants aged 40 to 70, was established across 22 centres in the UK between 2006 and 2010. After excluding missing values, prior AF history, and valvular heart disease, a total of 101,654 participants without AF (median age, 56.0 [interquartile range (IQR), 49.0–63.0] years; 44,851 [44.1%] male) were analyzed. Participants were divided into quartiles according to a validated PRS for AF. Throughout the observation period, the incidence of SSS event was documented. Results During a follow-up period of 11.7 (IQR 11.0-12.5) years, a total of 157 cases of Sick sinus syndrome were identified. In the new-onset SSS group, age, PRS for AF, BMI, and waist measurements were significantly higher. Additionally, there was a statistically significant increase in the proportions of male sex, hypertension, previous MI, hypothyroidism, dyslipidemia, and ESRD/CKD. The Kaplan-Meier analysis demonstrated an association between the highest quartile and an increased incidence of SSS compared to the other quartiles. (Log-rank P < 0.001) The Cox regression model revealed that a PRS for AF was associated with an increased risk of incidence of sick sinus syndrome (aHR 1.29, 95% CI 1.10-1.51, p-value 0.002). Notably, the discriminative power of our model was substantial, yielding a C-index of 0.746. Conclusion In our study, the PRS for AF effectively predicted the incidence of SSS. In the absence of a dedicated PRS for SSS, the AF PRS may offer insights into developing one for SSS.