Genomic knowledge in the context of diagnostic exome sequencing: changes over time, persistent subgroup differences, and associations with psychological sequencing outcomes

Purpose: People undergoing diagnostic genome-scale sequencing are expected tohave better psychological outcomes when they can incorporate and act onaccurate, relevant knowledge that supports informed decision making. Methods: This longitudinal study used data from the North Carolina ClinicalGenomic Evaluation by NextGen Exome Sequencing Study (NCGENES) of diagnosticexome sequencing to evaluate associations between factual genomic knowledge(measured with the University of North Carolina Genomic Knowledge Scale at threeassessments from baseline to after return of results) and sequencing outcomesthat reflected participants’ perceived understanding of the study andsequencing, regret for joining the study, and responses to learning sequencingresults. It also investigated differences in genomic knowledge associated withsubgroups differing in race/ethnicity, income, education, health literacy,English proficiency, and prior genetic testing. Results: Multivariate models revealed higher genomic knowledge at baselinefor non-Hispanic Whites and those with higher income, education, and healthliteracy (p values < 0.001). Thesesubgroup differences persisted across study assessments despite a generalincrease in knowledge among all groups. Greater baseline genomic knowledge wasassociated with lower test-related distress (p = 0.047) and greater perceived understanding of diagnosticgenomic sequencing (p values 0.04 to<0.001). Conclusion: Findings extend understanding of the role of genomic knowledge inpsychological outcomes of diagnostic exome sequencing, providing guidance foradditional research and interventions.