Review evaluates utility of GIRA high-risk genomic criteria across 9 adult conditions in 48279 patients

This retrospective evaluation assesses the utility of GIRA high-risk criteria, which incorporate monogenic and polygenic genomic components, for assessing health risk across 9 adult conditions. The study utilized data from the Penn Medicine Biobank, a health system independent of eMERGE, involving a sample size of 48279 adults. The primary outcome measured the utility of these criteria, while secondary outcomes included stratifying by ancestry, enrichments of high-risk individuals in social deprivation index, and prediction of prevalent and incident disease.

The analysis found that 30.4% of patients were labeled as high-risk, representing 14676 absolute numbers. High-risk classification rates were higher in African or African American populations at 56.6% versus 50.1%, and lower in East and South Asian ancestries at 42.0% and 40.0% respectively. A p-value of 7.43x10-36 was reported for these differences. Enrichments of high-risk individuals were observed in the highest quartile of social deprivation index.

The polygenic component served as a good predictor of prevalent cases. However, the GIRA prediction of incident disease showed lower accuracies for some conditions. Demographic composition of high-risk atrial fibrillation individuals was enriched for European ancestries, whereas incident AFIB cases were enriched for AFR ancestries. Safety data, including adverse events and tolerability, were not reported. Funding or conflicts were not reported.

The authors suggest potential impact on the health system if these criteria are implemented at scale. The study does not establish causality. Limitations regarding the retrospective nature and the specific setting are inherent to the design. Practice relevance is tempered by the lower accuracies for incident disease prediction in certain contexts.