Genetic Drivers of Cardiovascular Risk among South Asian Adults

South Asian individuals have been consistently shown to be at high risk for atherosclerotic cardiovascular disease. Traditional risk assessment tools such as clinical risk calculators have been shown to inaccurately capture risk in this population. Though South Asian individuals have a high prevalence of traditional risk factors, significant residual risk remains even after controlling for a multitude of traditional and non-traditional risk factors, suggesting the contribution of genetic influences. In this review, we discuss the available data regarding South Asians and genetic risk for coronary artery disease, with a focus on genetics underlying type 2 diabetes, obesity, dyslipidemia, and pharmacogenetics. We further review the increasing interest in polygenic risk scores and applications in this population.

Multiple genetic pathways have been implicated in coronary artery disease risk factors among South Asian adults. High rates of consanguinity in certain South Asian populations have enriched discovery cohorts with homozygous genotypes, which has enabled discovery of genetic pathways involved in multiple diseases such as hypertrophic cardiomyopathy and type 2 diabetes. Polygenic risk scores for coronary artery disease have been created and validated using cohorts of South Asian individuals, and newer methods including combining source genomes of multiple populations and combining risk scores for multiple related traits to optimize risk prediction have gained recent interest.

Genome wide association studies and polygenic risk scores hold promise in uncovering the genetic pathways behind the heightened cardiovascular risk found in South Asian populations and increasing the accuracy of cardiovascular risk prediction.