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Individuals with South Asian ancestry have higher risk of heart disease than other groups in Western countries; however, most genetic research has focused on European-ancestry (EUR) individuals. It is unknown whether reported genetic loci and polygenic scores (PGSs) for cardiometabolic traits are transferable to South Asians, and whether PGSs have utility in clinical settings.

Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort (G&H), we conducted genome-wide association studies (GWAS) and characterised the genetic architecture of coronary artery disease (CAD), body mass index (BMI), lipid biomarkers and blood pressure. We applied a new technique to assess the extent to which loci from GWAS in EUR samples were transferable. We tested how well existing findings from EUR studies performed in genetic risk prediction and Mendelian randomisation in G&H.

Trans-ancestry genetic correlations between G&H and EUR samples for the tested traits were not significantly lower than 1, except for BMI (r_g=0.85, p=0.02). We found evidence for transferability for the vast majority of loci from EUR discovery studies that were sufficiently powered to replicate in G&H. PGSs showed variable transferability in G&H, with the relative accuracy compared to EUR (ratio of incremental r²/AUC) ≥0.95 for HDL-C, triglycerides, and blood pressure, but lower for BMI (0.78) and CAD (0.42). We observed significant improvement in categorical net reclassification in G&H (NRI=3.9%; 95% CI 0.9–7.0) when adding a previously developed CAD PGS to …