Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality : Findings from the Finnish Twin Cohort
Joensuu, L., Waller, K., Kankaanpää, A., Palviainen, T., Kaprio, J., & Sillanpää, E. (2024). Genetic Liability to Cardiovascular Disease, Physical Activity, and Mortality : Findings from the Finnish Twin Cohort. Medicine and Science in Sports and Exercise, Ahead of Print. https://doi.org/10.1249/mss.0000000000003482
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Medicine and Science in Sports and ExerciseAuthors
Date
2024Access restrictions
Embargoed until: 2025-05-16Request copy from author
Copyright
© 2024 American College of Sports Medicine
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.
...


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Lippincott Williams & WilkinsISSN Search the Publication Forum
0195-9131Keywords
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https://converis.jyu.fi/converis/portal/detail/Publication/215880808
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- Liikuntatieteiden tiedekunta [3258]
Related funder(s)
Research Council of FinlandFunding program(s)
Academy Research Fellow, AoF; Research costs of Academy Research Fellow, AoFAdditional information about funding
The study was funded by the Academy of Finland (grant nos. 341750 and 346509 to ES and grant nos. 265240 and 263278 to JK), by the Juho Vainio Foundation (to ES), by the Päivikki and Sakari Sohlberg Foundation (to ES), and by the Sigrid Juselius Foundation (to JK). The phenotype and genotype data collection were funded by the Wellcome Trust Sanger Institute, the Broad Institute, the European Network for Genetic and Genomic Epidemiology (FP7-HEALTH-F4-2007, grant agreement no. 201413), and the Academy of Finland (grant nos. 100499, 205585, 118555, 141054, 264146, 308248, 312073, 336823 and 352792 to JK).

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