Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial)

Circulation. 2016 Mar 22;133(12):1181-8. doi: 10.1161/CIRCULATIONAHA.115.020109. Epub 2016 Feb 25.


Background: Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels.

Methods and results: Participants (n=203, 45-65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ((+)GRS). Participants in the (+)GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or (+)GRS (n=103). At the end of the study period, the (+)GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P=0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants (P=0.02) but not participants with low GRS (100.9±32.2 mg/dL; P=0.18). Statins were initiated more often in the (+)GRS group than in the CRS group (39% versus 22%, P<0.01). No significant differences in dietary fat intake and physical activity levels were noted.

Conclusions: Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone.

Clinical trial registration: URL: Unique identifier: NCT01936675.

Keywords: coronary disease; genetic risk disclosure; genetic risk score; genomics; hydroxymethylglutaryl-CoA reductase inhibitors; polymorphism, single-nucleotide; prevention & control; randomized clinical trials.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Anxiety / epidemiology
  • Cholesterol, LDL / blood*
  • Comorbidity
  • Coronary Disease / blood
  • Coronary Disease / epidemiology
  • Coronary Disease / genetics*
  • Coronary Disease / psychology
  • Decision Making
  • Dietary Fats
  • Female
  • Follow-Up Studies
  • Genetic Counseling
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Minnesota / epidemiology
  • Motor Activity
  • Patient Participation
  • Physician-Patient Relations
  • Polymorphism, Single Nucleotide
  • Probability
  • Risk Assessment
  • Risk Factors


  • Cholesterol, LDL
  • Dietary Fats
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors

Associated data