association of genetic susceptibility to smoking with cardiovascular disease mortality and the benefits of adhering to a DASH diet: The Singapore Chinese Health Study.

Background Understanding the genetic predisposition to cardiovascular disease (CVD) may help to improve clinical intervention strategies. Lifestyle factors, such as diet, may differ among ethnic groups and may, in turn, modify individuals' risks to diseases. Objectives We examined the genetic predisposition to ever smoking in relation to CVD mortality and assessed whether such an association could be modified by dietary intake. Methods A total of 23,760 Chinese adults from the Singapore Chinese Heath Study who were free of cancer and CVD at recruitment (1993–1998) were included in the study. A weighted genetic risk score (wGRS) was calculated to define the genetically determined regular smoking behavior (never or ever). Multivariable-adjusted Cox regression models were used to assess the association between the wGRS and CVD mortality. We also conducted a 1-sample Mendelian randomization analysis for ever smoking and CVD mortality. Results Over a mean of 22.6 years of follow-up, 2301 CVD deaths were identified. A genetic predisposition to ever smoking was significantly associated with CVD mortality; the multivariable-adjusted HR of CVD mortality was 1.07 (95% CI: 1.03–1.12), with a per-SD increment in the wGRS. However, the Mendelian randomization analysis did not support a causal relationship between ever smoking and CVD mortality (OR, 1.13; 95% CI: 0.87–1.45). Additionally, the Dietary Approaches to Stop Hypertension (DASH) score significantly modified the association between the smoking wGRS and CVD mortality; the association between a genetic predisposition to smoking and CVD mortality was only observed among individuals with a low DASH score (P- interaction = 0.004). Conclusions A genetic predisposition to smoking was associated with CVD mortality in the Chinese population. In addition, we detected a significant interaction showing higher CVD mortality related to genetically determined smoking among those with lower DASH scores. [ABSTRACT FROM AUTHOR]