Development and validation of the Vanderbilt PRS-KS, an instrument to quantify polygenic risk score knowledge

As polygenic risk scores (PRSs) enter clinical practice, health care providers' and the publics' comprehension of PRS results are of great importance; yet, they are poorly understood. We present the Vanderbilt polygenic risk scores knowledge scale (Vanderbilt PRS-KS), a tool to quantify PRS knowledge.

The Vanderbilt PRS-KS was developed by a team of genetic counselors and physicians to cover key conceptual facts pertaining to PRSs. We recruited (n = 500) individuals with demographics representative of a U.S. sample and graduate-level health care students (n = 74) at a large academic medical center to participate in this validation study. We evaluated the Vanderbilt PRS-KS's psychometric properties using confirmatory factor analysis and item response theory.

The 7-item Vanderbilt PRS-KS correlated to a single latent construct on confirmatory factor analysis (Λ = 0.31-0.61). The scale showed promising reliability (Cronbach's α = 0.66) with item response theory summed scores of ≥2 to ≤5, demonstrating reliability >0.70. The Vanderbilt PRS-KS significantly correlated with genetic knowledge and applied PRS knowledge (r = 0.55 and r = 0.29), and graduate-level health care students scored significantly higher compared with the U.S. representative sample (P < .01).

The Vanderbilt PRS-KS is a rigorously validated measure to quantify PRS knowledge. Clinicians should tailor future PRS knowledge interventions to the identified knowledge gaps, including PRS inheritance, equity of performance in different ethnicities, and integration with other health determinants.