| Title: | Self-reported walking pace, polygenic risk scores and risk of coronary artery disease in UK Biobank |
| Journal: | Nutrition Metabolism and Cardiovascular Diseases |
| Published: | 1 Sep 2022 |
| DOI: | https://doi.org/10.1016/j.numecd.2022.08.021 |
| URL: | http://www.nmcd-journal.com/article/S0939475322003635/pdf |
Publication 7054
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Abstract
Background and Aims Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. Methods and Results We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006-Feb/2021.In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30-3.13) in women; 9.60% (8.62-10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81-1.71) in women; 3.63% (2.58-4.67) in men] than lower [0.76% (0.59-0.93) and 2.37% (1.96-2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793-0.808) in women; 0.732 (0.728-0.737) in men. Conclusion Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.8 Authors
- Francesco Zaccardi
- Iain R. Timmins
- Jonathan Goldney
- Frank Dudbridge
- Paddy C. Dempsey
- Melanie J. Davies
- Kamlesh Khunti
- Thomas Yates
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