Polygenic Risk Score to Identify Subclinical Coronary Heart Disease Risk in Young Adults

Circ Genom Precis Med. 2021 Oct;14(5):e003341. doi: 10.1161/CIRCGEN.121.003341. Epub 2021 Aug 31.


Background: Polygenic risk scores (PRS) may enhance risk stratification for coronary heart disease among young adults. Whether a coronary heart disease PRS improves prediction beyond modifiable risk factors in this population is not known.

Methods: Genotyped adults aged 18 to 35 years were selected from the CARDIA study (Coronary Artery Risk Development in Young Adults; n=1132) and FOS (Framingham Offspring Study; n=663). Systolic blood pressure, total and HDL (high-density lipoprotein) cholesterol, triglycerides, smoking, and waist circumference or body mass index were measured at the visit 1 exam of each study, and coronary artery calcium, a measure of coronary atherosclerosis, was assessed at year 15 (CARDIA) or year 30 (FOS). A previously validated PRS for coronary heart disease was computed for each subject. The C statistic and integrated discrimination improvement were used to compare improvements in prediction of elevated coronary artery calcium between models containing the PRS, risk factors, or both.

Results: There were 62 (5%) and 93 (14%) participants with a coronary artery calcium score >20 (CARDIA) and >300 (FOS), respectively. At these thresholds, the C statistic changes of adding the PRS to a risk factor-based model were 0.015 (0.004-0.028) and 0.020 (0.001-0.039) in CARDIA and FOS, respectively. When adding risk factors to a PRS-based model, the respective changes were 0.070 (0.033-0.109) and 0.051 (0.017-0.079). The integrated discrimination improvement, when adding the PRS to a risk factor model, was 0.027 (-0.006 to 0.054) in CARDIA and 0.039 (0.0005-0.072) in FOS.

Conclusions: Among young adults, a PRS improved model discrimination for coronary atherosclerosis, but improvements were smaller than those associated with modifiable risk factors.

Keywords: atherosclerosis; blood pressure; coronary artery; heart disease; risk factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index
  • Calcium / blood*
  • Cholesterol, HDL / blood*
  • Cohort Studies
  • Coronary Disease / blood*
  • Female
  • Humans
  • Male
  • Risk
  • Risk Assessment
  • Smoking / adverse effects
  • Smoking / blood
  • Triglycerides / blood*
  • Young Adult


  • Cholesterol, HDL
  • Triglycerides
  • Calcium