A genetic risk score based on 5 susceptibility loci was associated with increased coronary heart disease risk in diabetic patients (OR 1.19 per unit; 95% CI 1.13-1.26; P<0.0001).
Case-Control (n=2,506)
Yes
Does a genetic risk score based on established susceptibility loci predict coronary heart disease in patients with type 2 diabetes?
A genetic risk score based on 5 established susceptibility loci significantly improves the prediction of coronary heart disease in patients with type 2 diabetes when added to clinical predictors.
Odds Ratio: 1.19 (95% CI 1.13–1.26)
p-value: p=<0.0001
Objective To evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes. Background No study has examined the effects of these genetic variants on CHD in diabetic patients. Methods We genotyped 15 genetic markers of 12 loci in three studies of diabetic patients: the prospective Nurses’ Health Study (309 CHD cases and 544 controls) and Health Professional Follow-up Study (345 CHD cases and 451 controls), and the cross-sectional Joslin Heart Study (422 CHD cases and 435 controls). Results Five SNPs, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the three studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p=0.03 to 0.0002). None of the other SNPs reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the five significantly associated loci. The OR of CHD per GRS unit was 1.19 (95% confidence interval CI 1.13– 1.26; p<0.0001). Individuals with GRS ≥8 (19% of diabetic subjects) had almost a two-fold increase in CHD risk (OR=1.94, 95% CI 1.60–2.35) as compared to individuals with GRS ≤5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p<0.001) when the GRS was added to a model including clinical predictors in the combined samples. Conclusions Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.
“The effect is not dramatic, but it is much better than what we expected”
Qi et al. (Thu,) conducted a case-control in Coronary heart disease in type 2 diabetes (n=2,506). Genetic risk score (GRS) of 5 CHD-susceptibility loci vs. Lower genetic risk score was evaluated on Coronary heart disease (CHD) (OR 1.19, 95% CI 1.13-1.26, p=<0.0001). A genetic risk score based on 5 susceptibility loci was associated with increased coronary heart disease risk in diabetic patients (OR 1.19 per unit; 95% CI 1.13-1.26; P<0.0001).