Elevated incidence of CHD attributable to smoking was less prominent in those with a genetic predisposition to CHD than in those without it, according to a study published in Circulation: Genomic and Precision Medicine.
George Hindy, MD, PhD, postdoctoral research fellow at the Broad Institute of Massachusetts Institute of Technology and Harvard University, and colleagues analyzed data from 24,443 participants (mean age, 58 years; 62% women) from the Malmö Diet and Cancer Study. Patients completed questionnaires on their physical activity, smoking habits, medication history, education and diet history. Nurses also measured BP and took blood samples. Participants were excluded if they had prevalent CHD.
CHD was defined as CABG, fatal or nonfatal MI, PCI or death caused by ischemic heart disease.
Participants were categorized based on their smoking status: never smokers, former smokers and current smokers. Genotyping was performed, and each participant was given a polygenic risk score based on presence or absence of 50 single nucleotide polymorphisms known to be associated with CHD. Follow-up was conducted for a median of 19.4 years.
During follow-up, 13.2% of participants developed CHD. The polygenic risk score modified the increased risk for CHD associated with smoking (P for interaction = .005).
Participants in the lowest tertile for polygenic risk score had the highest magnitude of increased incidence of CHD caused by smoking (OR per smoking risk category = 1.42; 95% CI, 1.29-1.56) compared with those in the highest tertile (OR per smoking risk category = 1.2; 95% CI, 1.11-1.3). Men had a stronger interaction (P for interaction = .001) compared with women (P for interaction = .44). Family history did not affect CHD associated with smoking.
The polygenic risk score improved net reclassification and discrimination when added to traditional risk factors in participants who never smoked, but such improvements were not seen in current smokers (P < .001).
“Our results show that smoking status may provide a valuable stratification tool for prioritization of individuals who would benefit from using a [polygenic risk score] to improve prediction of future CHD,” Hindy and colleagues wrote. “The [polygenic risk score] provided better discrimination on the top of a traditional risk factor model among never smokers compared with smokers.”
In a related editorial, Roberto Elosua, MD, PhD, of the cardiovascular epidemiology and genetics group at Institut Hospital del Mar d’Investigacions Mediques in Barcelona, Spain, wrote: “Hindy et al use an alternative method, defining a genetic risk score and analyzing the interaction between this genetic risk load and smoking on CAD. This approach is becoming more popular and could contribute to the identification of subgroups of the population that would obtain higher benefits from modifying their exposure to the environmental factor under study.” – by Darlene Dobkowski
The authors and Elosua report no relevant financial disclosures.