Polygenic risk scores in kidney transplantation

Estimation of genetic risk is crucial for understanding heritable diseases but also transplant outcomes. Polygenic risk scores (PRSs) are constructed from genome-wide association studies (GWAS) summing an individual's risk alleles weighted by their effect size. Introducing PRSs into transplant medicine may improve predictions of outcomes such as rejection, graft loss or death. This review of recent publications highlights the additional variability in outcomes explained by PRSs beyond established clinical models. Four studies on PRSs in transplantation have examined outcomes such as acute rejection, changes in posttransplant estimated glomerular filtration rate (eGFR) and posttransplant diabetes mellitus (PTDM) and explored the role of donor polygenic burden for cerebrovascular traits. PRSs have been showing utility in predicting PTDM [adjusted odds ratio (OR):1.48 (95% confidence interval (CI): 1.06, 2.08]. A PRS based on a non-HLA alloimmunity GWAS explained additional variability for acute rejection [adjusted hazard ratio (HR): 1.54, 95% CI: 1.07, 2.22]. Donor PRSs for hypertension and cerebrovascular traits correlated with lower recipient eGFR (HR: 1.44, 95% CI: 1.07, 1.93). Genetic variation was also linked to long-term kidney function, though clinical variables explained a greater proportion of the variability (0.3% vs. 32%). Currently, PRSs modestly enhance outcome prediction in transplantation when added to clinical models. With a more biologically based selection of variants, PRSs may gain greater value in transplant risk assessment.