Genome-wide polygenic risk score in premature coronary artery disease in India

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Abstract Background & Objective Premature coronary artery disease (CAD) is an important problem in developing countries. This study was performed to identify the importance of South Asia-specific genome-wide polygenic risk score (GPRS) for risk assessment in patients with angiographically confirmed CAD in India. Methods Successive patients (n=1042) with CAD who underwent coronary angiography were included and divided into 1-4 age-groups (<40, 40-49, 50-59 and 60+ years). Details of risk factors and the extent of CAD were recorded. A multi-ancestry GPRS model comprising of 1.3 million SNPs validated in the South Asian population was used for classification into average-, moderate-, and high-risk groups. Descriptive statistics are presented. Results Clinical and genetic data were available in 993 participants (men 86.1%). Risk factors were CAD family history 41.2%, tobacco 31.0%, hypertension 41.9%, diabetes 37.3%, LDL cholesterol >70mg/dl 77.3%, non-HDL cholesterol >100mg/dl 70.0%, and triglycerides >150mg/dl 46.3%. Group 1 (>40 years) had the highest prevalence of CAD family history, tobacco, and raised LDL-cholesterol, non-HDL cholesterol and triglycerides, while Groups 3 and 4 had significantly more hypertension and diabetes (p<0.01). Group 1 patients had more ST-elevation myocardial infarction, better ejection fraction and single-vessel CAD (p<0.01). GPRS followed a Gaussian distribution with a mean score 0.19 (IQR: -0.47 to 0.86) with the highest score in Group 1 [0.46 (IQR -0.18 to 1.28)] compared to others (p<0.001). Overall, the average risk was in 45.6%, moderate risk in 33.1% and high risk in 21.2%. In Groups 1 to 4, respectively, moderate- and high-risk were in 64.1%, 57.8%, 51.7% and 45.7% (p<0.01). Compared to Group 4, the multivariate-adjusted odds ratios (logistic regression) were in Group 1: 2.32 (95% CI 1.18-4.55); Group 2: 1.36 (95% CI 0.76-3.43) and Group 3: 1.02 (95% CI 0.58-1.79) (Figure 1). Conclusion: Premature CAD patients in India have significantly higher GPRS and more are in moderate and high genetic risk categories. The genetic risk persists following adjustment for major coronary risk factors.Figure 1

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