Non-Random Enrichment of Single Nucleotide Polymorphisms Associated with Clopidogrel Resistance within Risk Loci Linked to the Severity of Underlying Cardiovascular Diseases: Role of Admixture

Cardiovascular disease (CVD) is one of the leading causes of death in Puerto Rico, where clopidogrel is commonly prescribed to prevent ischemic events. Genetic contributors to both a poor clopidogrel response and the severity of CVD have been identified mainly in Europeans. However, the non-random enrichment of single nucleotide polymorphisms (SNPs) associated with clopidogrel resistance within risk loci linked to underlying CVDs, and the role of admixture, has yet to be tested. This study aimed to assess possible interaction between genetic biomarkers linked to CVDs and those associated with clopidogrel resistance among admixed Caribbean Hispanics. We identified 50 SNPs significantly associated with CVDs in previous genome-wide association studies (GWAS). These SNPs were combined with another ten SNPs related to clopidogrel resistance in Caribbean Hispanics. We developed Python scripts to determine whether SNPs related to CVDs are in close proximity to those associated with clopidogrel response. Average and individual local ancestry (LAI) within each locus were inferred, and 60 random SNPs with their corresponding LAI were generated for enrichment estimation purposes. Our results showed no CVD-linked SNPs in close proximity to those associated with clopidogrel response among Caribbean Hispanics. Consequently, no genetic loci with a dual predictive role for risk of CVD severity and clopidogrel resistance were found in this population. Native American ancestry was the most enriched within risk loci linked to CVDs in this population. Non-random enrichment of disease susceptibility loci with drug response SNPs is a new frontier in Precision Medicine that needs further attention.