Polygenic risk scores for atrial fibrillation and heart failure and the risk of stroke and dementia - a population-based study

Abstract

Introduction: Atrial fibrillation (AF) is a known risk factor for stroke and heart failure (HF). In addition, individuals with HF have an increased risk for AF. An increasing body of evidence have also linked AF to dementia, while less is known regarding the relation between HF and dementia. We aim to investigate if higher genetic risk, measured with polygenic risk scores (PRSs), for AF and HF increases dementia and stroke risk in the general population. Methods: Data was obtained from the Gothenburg H70 Birth Cohort Studies. The participants were born 1930 and were systematically selected from the Swedish population register based on birth dates. The first examination was conducted at age 70 in 2000-02. Thereafter, examinations have been conducted up to age 88. Stroke diagnoses were based on self- and proxy-reports, and hospital registers. Dementia was diagnosed according to the DSM-III-R criteria based on neuropsychiatric examinations, proxy- reports, and hospital registers. The PRSs were based on summary statistics from large GWASs and include PRSs on the 5*10-8, 1*10-7, 1*10-6, 1*10-5, 1*10-4, 1*10-3, 1*10-2, and 0.1 significance levels. The PRSs were standardized, and cox-regressions adjusted for sex, inclusion year in the study, and the five first principal components were performed. Risk years from birth until development of the outcome, death, emigration, or the end of the study, were calculated. Results: A total of 984 participants, of whom 250 developed dementia and 238 developed a stroke, were included. Participants with higher HF-PRS had an increased dementia risk (HR 1.2; p=0.009) but no increased stroke risk. On the contrary, participants with higher AF-PRS had increased stroke risk (HR 1.2, p=0.032), but no increased dementia risk. Discussion: Our findings support causality between HF and dementia, while the previously shown association between AF and dementia might be explained by shared risk factors between AF and dementia, or an increased risk of stroke and HF in AF patients. However, a potential lack of an association between AF-PRS and dementia needs to be confirmed in larger studies.