Genetic Risk Score for Coronary Disease in People With Type 1 Diabetes

Coronary heart disease (CHD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries.
Glycemic control and cholesterol levels have been used as predictors of coronary artery disease in type 1 diabetes. Investigators sought a genetic predictor as well.

A genetic risk score (GRS) in people with type 1 diabetes (T1D) may predict if they are at risk for coronary artery disease, according to findings published in Diabetes Care.  Additionally, this GRS was found to have a similar predictive risk power as traditional clinical predictive risk factors like glycated hemoglobin (HbA1C) and high-density lipoprotein cholesterol (HDL-C)  levels.

This analysis was part of the Finnish Diabetic Nephropathy (FinnDiane) study, an ongoing, nationwide, multicenter study with the goal of identifying potential risk factors for complications associated with T1D. Patients (N=3295) with T1D were evaluated for their clinical risk for coronary artery disease (CAD) risk and genetic risk score (GRS) and followed from 1997 through 2015 for CAD events. Clinical risk for CAD was calculated by 8 predictors: diabetes duration, age of diabetes onset, the ratio of total cholesterol to HDL-C, HbA1C, systolic blood pressure, macroalbuminuria, cardiovascular disease history, and smoking status. Genetic risk score was calculated on the basis of 156 currently known CAD risk variants.

The group of study participants were 51% men aged mean 39.1±11.2 years, and had a mean duration of diabetes of 22.9±11.7 years at baseline.

During a median 14.8-year follow-up, 467 individuals developed CAD. Stratified by CAD status, the CAD cohort was older (P =3.0´10-60) than participants in the control group who did not develop the disease had a longer duration of diabetes (P =2.2´10-71), diabetes onset at a younger age (P =.01), and had more traditional CAD risk factors and comorbidities.

The average GRS for the CAD cohort was 0.0086±0.0032, which was significantly higher than those who did not develop CAD (mean, 0.0078±0.0032; P =7.7´10-7).

Individuals who had a GRS in the highest 5th percentile were associated with a 6.7-fold increased risk for CAD compared with those in the lowest 5th percentile.

Survival models of GRS risk were similar (C-index, 0.562; 95% CI, 0.535-0.589) compared with clinical risk predictors: HbA1C (C-index, 0.563; P =1.0), HDL-C (C-index, 0.571; P =.6), low-density lipoprotein cholesterol (C-index, 0.598; P =.064), and total cholesterol (C-index, 0.594; P =.1).

The strongest CAD predictors were age (hazard ratio [HR], 1.78; P =1.77´10x17), diabetic nephropathy status (HR, 1.64; P =1.93´10x23), GRS (HR, 1.31; P =2.26´10x8), triglycerides (HR, 1.20; P =.00235), systolic blood pressure (HR, 1.19; P =.00151), HbA1C (HR, 1.19; P =.00054), HDL-C (HR, 0.82; P =.000594), and year of diabetes onset (HR, 0.62; P =4.88´10x11).

Risk stratification was modestly improved by incorporating GRS with clinical risk prediction (C-index for clinical score 0.813 vs combined score 0.820, P =.003).

Stratified by age, the GRS predictive model was better fit among those aged <38.6 years (C-index, 0.637; 95% CI, 0.580-0.695) than for patients aged ³38.6 years (C-index, 0.546; 95% CI, 0.516-0.577).

Although the researchers described this study as the largest genetic study of T1D risk for CAD, thus far, they acknowledged it was limited by its small sample size.

While acknowledging some data remained inconclusive, the researchers concluded GRS was a valuable predictor of CAD in people with T1D, particularly in younger patients.

“A GRS may be a novel and independent biomarker for clinical use in CAD event prediction in the younger individuals with type 1 diabetes and allows preventative action and early intervention steps to be taken at an early stage among high-risk individuals,” the researchers wrote.

Disclosure: Some study authors declared affiliations with pharmaceutical and other private companies.  Please see the original reference for a full list of authors’ disclosures.


Lithovius R, Antikainen AA, Mutter S, et al. Genetic risk score enhances coronary artery disease risk prediction in individuals with type 1 diabetes. Diabetes Care. 2022;dc210974. doi:10.2337/dc21-0974