Using a genetic risk score to calculate the optimal age for an individual to undergo coronary artery calcium screening

J Cardiovasc Comput Tomogr. 2019 Jul-Aug;13(4):203-210. doi: 10.1016/j.jcct.2019.05.005. Epub 2019 May 9.


Background: Genetic risk scores (GRSs) have been associated with CHD events and coronary artery calcium (CAC). We sought to evaluate the ability of a GRS to improve CAC as a screening test.

Methods: Using the results of the most recent genome-wide association studies, we calculated a GRS in 6660 individuals from the Multi-Ethnic Study of Atherosclerosis and used it to determine the optimal age for an individual to undergo CAC screening.

Results: This 157-SNP GRS was predictive of non-zero CAC in individuals aged 44-54 and improved the positive yield of CAC as a screening test in this age group. The GRS was predictive of CAC in the entire multi-ethnic cohort and in each self-identified ethnic group (European American, Chinese American, African American, and Hispanic American) assessed individually. Given a specified target yield rate of non-zero CAC, an equation was derived to calculate an individual's optimal age to undergo CAC screening. In addition, a "direct-to-consumer" GRS consisting of only risk SNPs or their proxies that are directly genotyped on the 23andMe v5 chip (102-SNP GRS) was assessed in the European American population and was predictive of non-zero CAC in younger individuals.

Conclusion: A GRS is associated with non-zero CAC in a multi-ethnic cohort and can be used to calculate the age of a person's first calcium scan, given a target threshold for CAC discovery. Furthermore, an inexpensive and widely available "direct-to-consumer" GRS was found to be a viable option to calculate the optimal age for CAC screening.

Keywords: CAC; Coronary artery calcium; Coronary heart disease; Genetic risk score; Genetics; Screening.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Clinical Decision-Making
  • Coronary Angiography*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology
  • Vascular Calcification / diagnostic imaging*
  • Vascular Calcification / ethnology
  • Vascular Calcification / genetics*