Validity of European-centric derived cardiometabolic polygenic risk scores in multi-ancestry populations

ABSTRACT Polygenic risk scores (PRSs) provide an individual level estimate of genetic risk for any given disease. Since most PRSs have been derived from genome wide association studies (GWAS) conducted in populations of White European ancestry, their validity in other ancestry groups remains unconfirmed. This is especially relevant for cardiometabolic diseases which are known to disproportionately affect people of non-European ancestry. Thus, we aimed to evaluate the performance of PRSs for glycaemic traits (glycated haemoglobin, type 1, and type 2 diabetes mellitus), cardiometabolic risk factors (body mass index, hypertension, high- and low-density lipoproteins, and total cholesterol and triglycerides) and cardiovascular diseases (CVDs, including stroke and coronary artery disease) in people of White European, South Asian, and African Caribbean ethnicity in the UK Biobank. Whilst the PRSs incorporated some GWAS data from multi-ethnic population, the vast majority originated from White Europeans. Except for hypertension and stroke, PRSs derived mostly from European populations had an overall better performance in White Europeans compared to South Asians and African Caribbeans. Thus, multi-ancestry GWAS data are needed to generate ancestry stratified PRSs to tackle health inequalities.