Mode Of Transport, Genetic Susceptibility, And Incidence Of Coronary Heart Disease

Abstract

PURPOSE: Using an inactive transport mode, such as cars, is a risk factor of coronary heart disease (CHD). However, whether the associations of transport mode with CHD vary by genetic susceptibility to CHD are unknown. This study aims to investigate the interaction between genetic susceptibility and transport mode in relation to incidence of CHD. METHODS: We included 364,560 white British participants from UK Biobank with no CHD at baseline. Genetic risk for CHD was quantified through polygenic risk scores, calculated based on 300 single-nucleotide polymorphisms related to CHD risk. Categories of transport mode included exclusive use of cars and more active patterns of travel (e.g., walking, cycling and public transport), separately for non-commuting (e.g., getting about; in the full sample [n = 364,560]) and commuting (in the sub-set [n = 188,816] who responded to the commuting question). Hazard ratios (HR) for incident CHD (n = 9,686; median 12.1-year follow-up), as well as the interaction between genetic risk and travel modes were estimated using Cox regression with age as the underlying timescale. RESULTS: The HRs of CHD were 1.45 (95% CI: 1.37-1.53) and 2.06 (95% CI: 1.96-2.17) for middle and high genetic risk, respectively, compared with low genetic risk, after adjusting for age, sex, lifestyle factors and other confounders. Compared with an active mode of transport, hazards of CHD were higher for exclusive use of cars for either non-commuting [HR: 1.08(1.04-1.13)] or commuting [HR: 1.16(1.08-1.25)], after adjusting for confounders including genetic susceptibility. Compared with the joint reference category of low genetic risk and active travel patterns for non-commuting, the hazards for CHD were relatively higher for exclusive use of cars for non-commuting in combination with moderate [HR:1.59(1.47-1.72)]or high genetic risk [HR: 2.23(2.07-2.40)]: similar joint associations were observed for the commuting categories combined with three categories of genetic risk. CONCLUSIONS: Exclusive use of cars for either commuting or non-commuting was associated with an increased risk of CHD at all levels of genetic risk including high genetic risk. Community-based interventions customized to individuals with high genetic risk should focus on promoting a more active transport mode to prevent CHD.