Associations of genetic and infectious risk factors with coronary heart disease

Elife. 2023 Feb 14:12:e79742. doi: 10.7554/eLife.79742.


Coronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD. Study participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every 5 years. We analyzed a subgroup of 3459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses. Of the 3459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status, and statin intake, revealed that high polygenic risk (hazard ratio [HR] 1.31, 95% CI 1.10-1.56, p=2.64 × 10-3) and infection with Fusobacterium nucleatum (HR 1.63, 95% CI 1.08-2.45, p=1.99 × 10-2) were independently associated with incident CHD. In a prospective, population-based cohort, high polygenic risk and infection with F. nucleatum have a small, yet independent impact on CHD risk.

Keywords: Cox regression; coronary heart disease; genetics; genomics; human; human genomics; inflammation; persistent infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Disease* / epidemiology
  • Coronary Disease* / genetics
  • Humans
  • Incidence
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.