The Interaction Between Genetic Factors and Sleep Duration Associated with Coronary Artery Disease Público
Osei, Jeffery (Spring 2023)
Abstract
Background: Although genetic and lifestyle factors such as sleep duration contribute to the development of coronary artery disease (CAD), it is unclear whether sleep duration modifies the effect of genetic predisposition on CAD outcomes.
Methods: We examined the relationship between several polygenic risk scores (comprehensive CAD PRS, and PRSs of three risk factors) and CAD outcomes, as well as the interaction with sleep duration, in 354,845 participants of European ancestry in the UK Biobank. We fitted cox proportional hazard and Fine-Gray competing risk models and assessed PRS-sleep duration interaction on both additive and multiplicative scales.
Results: After excluding 14, 283 participants who had prevalent CAD at baseline, 354,845 people were followed for up to 12.0 (11.2-12.8) years. Out of this, 82,568 (23.2%), 266,745 (75.2%), and 5,532 (1.6%) had less than 7 hours of sleep/day, 7-9 hours of sleep/day, and more than 9 hours of sleep/day, respectively. We found a significant multiplicative gene-sleep duration interaction (PRSCAD´Sleep) for new onset CAD. The risk was highest among participants with 7-9 hours of sleep/day (hazard ratio [HR] for 1 SD increase in genetic risk 1.39 [95% CI, 1.37-1.41]; compared with low genetic risk, HR for intermediate genetic risk 1.56 [95% CI, 1.49-1.64] and HR for high genetic risk 2.51 [95% CI, 2.39-2.64]). Participants with more than 9 hours of sleep/day had the lowest risk (HR for 1 SD increase in genetic risk 1.24 [95% CI, 1.15-1.34]; compared with low genetic risk, HR for intermediate genetic risk 1 .31 [95% CI, 1.06-1.64] and HR for high genetic risk 1.75 [95% CI, 1.37-2.23]). However, on the additive scale, there was no evidence of interaction. Additionally, Among the PRSs of three risk factors, we found a significant antagonistic interaction between hypertension-based PRS (PRSHTN) and sleep duration for CAD death at both additive and multiplicative scales.
Conclusions: Further validation of the interaction between genetic factors and sleep duration associated with CAD is warranted. The assessment of gene-environment interaction on both multiplicative and additive scales could aid in understanding the complex interplay between risk factors and mechanisms underlying CAD. Robust gene-environment interaction effects would guide future public health preventive strategies for CAD.
Table of Contents
Table of Contents
1.0 INTRODUCTION
2.0 METHODS
2.1 Study population
Figure 1.0 Flow chart of the study population inclusion/exclusion criteria used for this study
2.2 Ascertainment of outcome
2.3 PRS construction
2.4 Ascertainment of sleep duration and other covariates
2.5 Statistical analyses
3.0 RESULTS
3.1 Population Characteristics
Table 1. Baseline characteristics of 354,845 UK Biobank participants of European Ancestry by Sleep Duration
3.2 Association between genetic susceptibility and prevalent CAD
3.3 Association of sleep duration and genetic susceptibility with incident CAD
Table 2. Association of comprehensive CAD-PRS and three risk factor-based PRSs with prevalent CAD in the UK Biobank
Table 3. Combined association of genetic predisposition (PRSs) and sleep duration with incident CAD in the UK Biobank
Figure 2. Relative excess risk due to interaction (RERI) for CAD polygenic risk scores and sleep duration on CAD outcomes. (Reference group is low PRS with 7-9 hours of sleep/day)
3.4 Association of sleep duration and genetic susceptibility with CAD death
3.5 Association of sleep duration and genetic susceptibility with composite CAD outcomes
Table 4. Combined association of genetic predisposition (PRSs) and sleep duration with CAD death in the UK Biobank
Table 5. Combined association of genetic predisposition (PRSs) and sleep duration with composite CAD outcomes* in the UK Biobank
4.0 DISCUSSION
5.0 CONCLUSION
6.0 REFERENCES
About this Master's Thesis
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