TY - JOUR

T1 - Interaction of genetic risk and lifestyle on the incidence of atrial fibrillation

AU - Frederiksen, Tanja Charlotte

AU - Christiansen, Morten Krogh

AU - Benjamin, Emelia J.

AU - Overvad, Kim

AU - Olsen, Anja

AU - Andersen, Mette K.

AU - Hansen, Torben

AU - Grarup, Niels

AU - Jensen, Henrik Kjaerulf

AU - Dahm, Christina C.

N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2023

Y1 - 2023

N2 - Background: The relationship between combined genetic predisposition and lifestyle and the risk of incident atrial fibrillation (AF) is unclear. Therefore, we aimed to assess a possible interaction between lifestyle and genetics on AF risk. Methods: We included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. Lifestyle risk factors were assessed, a score was calculated, and participants were categorised as having a poor, intermediate, or ideal lifestyle. We calculated a genetic risk score comprising 142 variants, and categorised participants into low (quintile 1), intermediate (quintiles 2-4) or high (quintile 5) genetic risk of AF. Results: 3094 AF cases occurred during a median follow-up of 12.9 years. Regardless of genetic risk, incidence rates per 1000 person-years were gradually higher with worse lifestyle. For participants with high genetic risk, the incidence rates of AF per 1000 person-years were 5.0 (95% CI 3.4 to 7.3) among individuals with ideal lifestyle, 6.6 (95% CI 5.4 to 8.1) among those with intermediate lifestyle and 10.4 (95% CI 9.2 to 11.8) among participants with poor lifestyle. On an additive scale, there was a positive statistically significant interaction between genetic risk and lifestyle (relative excess risk due to interaction=0.86, 95% CI 0.68 to 1.03, p<0.001). Conclusions: The rates of AF increased gradually with worse lifestyle within each category of genetic risk. We found a positive interaction on an additive scale between genetic risk and lifestyle, suggesting that risk factor modification is especially important in individuals with a high genetic risk of AF.

AB - Background: The relationship between combined genetic predisposition and lifestyle and the risk of incident atrial fibrillation (AF) is unclear. Therefore, we aimed to assess a possible interaction between lifestyle and genetics on AF risk. Methods: We included AF cases and a randomly drawn subcohort of 4040 participants from the Danish Diet, Cancer and Health cohort. Lifestyle risk factors were assessed, a score was calculated, and participants were categorised as having a poor, intermediate, or ideal lifestyle. We calculated a genetic risk score comprising 142 variants, and categorised participants into low (quintile 1), intermediate (quintiles 2-4) or high (quintile 5) genetic risk of AF. Results: 3094 AF cases occurred during a median follow-up of 12.9 years. Regardless of genetic risk, incidence rates per 1000 person-years were gradually higher with worse lifestyle. For participants with high genetic risk, the incidence rates of AF per 1000 person-years were 5.0 (95% CI 3.4 to 7.3) among individuals with ideal lifestyle, 6.6 (95% CI 5.4 to 8.1) among those with intermediate lifestyle and 10.4 (95% CI 9.2 to 11.8) among participants with poor lifestyle. On an additive scale, there was a positive statistically significant interaction between genetic risk and lifestyle (relative excess risk due to interaction=0.86, 95% CI 0.68 to 1.03, p<0.001). Conclusions: The rates of AF increased gradually with worse lifestyle within each category of genetic risk. We found a positive interaction on an additive scale between genetic risk and lifestyle, suggesting that risk factor modification is especially important in individuals with a high genetic risk of AF.

KW - Atrial Fibrillation

KW - Epidemiology

KW - Genetics

U2 - 10.1136/heartjnl-2023-323333

DO - 10.1136/heartjnl-2023-323333

M3 - Journal article

C2 - 38016806

AN - SCOPUS:85178639616

JO - Heart

JF - Heart

SN - 1355-6037

ER -