Clinical utility of polygenic risk scores: a critical 2023 appraisal

Since their first appearance in the context of schizophrenia and bipolar disorder in 2009, polygenic risk scores (PRSs) have been described for a large number of common complex diseases. However, the clinical utility of PRSs in disease risk assessment or therapeutic decision making is likely limited because PRSs usually only account for the heritable component of a trait and ignore the etiological role of environment and lifestyle. We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare. In conclusion, the benefit to individual patients or the health care system in general of PRS-based extensions of existing diagnostic or treatment regimens is still difficult to judge. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12687-023-00645-z.