Marital status and genetic liability independently predict coronary heart disease incidence

Aims: Married individuals have a lower coronary heart disease (CHD) risk than non-married, but the mechanisms behind this are not fully understood. We analyzed whether genetic liability to CHD may affect these associations. Methods: Marital status, a polygenic score of CHD (PGS-CHD), and other risk factors for CHD were measured from 35,444 participants (53% female) in Finnish population-based surveys conducted between 1992 and 2012. During the register-based follow-up until 2020, there were 2439 fatal and non-fatal incident CHD cases. The data were analyzed using linear and Cox regression models. Results: Divorced and cohabiting men and women had a higher genetic risk of CHD than married individuals, but the difference was very small (0.023-0.058 standard deviation of PGS-CHD, p-values 0.011-0.429). Both marital status and PGS-CHD were associated with CHD incidence, but the associations were largely independent. Adjusting for behavioral and metabolic risk factors for CHD explained part of these associations (11-20%). No interaction was found between marital status and PGS-CHD for CHD incidence. Conclusions: We showed minor differences between the marital status categories in PGS-CHD and demonstrated that marital status and genetic liability predicted CHD incidence largely independently. This emphasizes the need to measure multiple risk factors when predicting CHD risk.