Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality : Findings from the Finnish Twin Cohort

Purpose We investigated whether longitudinally assessed physical activity (PA) and adherence specifically to World Health Organization PA guidelines mitigates or moderates mortality risk regardless of genetic liability to cardiovascular disease (CVD). We also estimated the causality of the PA-mortality association. Methods The study used the older Finnish Twin Cohort (FTC) with 4,897 participants aged 33–60 years (54.3% women). Genetic liability to coronary heart disease, systolic and diastolic blood pressure was estimated with polygenic risk scores (PRSs) derived from the Pan-UK Biobank (N ≈ 400,000; > 1,000,000 genetic variants). Leisure-time PA was assessed with validated and structured questionnaires three times during 1975–1990. The main effects of adherence to PA guidelines and the PRS × PA interactions were evaluated with Cox proportional hazards models against all-cause and CVD mortality. A co-twin control design with 180 monozygotic twin pairs discordant for meeting the guidelines was used for causal inference. Results During the 17.4-year (mean) follow-up (85,136 person-years), 1,195 participants died, with 389 CVD deaths. One standard deviation higher PRSs were associated with a 17%–24% higher CVD mortality risk but not with all-cause mortality except for the PRS for diastolic blood pressure. Adherence to PA guidelines did not show significant independent main effects or interactions with all-cause or CVD mortality. Twins whose activity levels adhered to PA guidelines over a 15-year period did not have statistically significantly reduced mortality risk compared to their less active identical twin sibling. The findings were similar among high, intermediate, and low genetic risk levels for CVD. Conclusions The genetically informed FTC data could not confirm that adherence to PA guidelines either mitigates or moderates genetic CVD risk or causally reduces mortality risk.