Risk perception and intended behavior change after uninformative genetic results for adult-onset hereditary conditions in unselected patients.

Population genetic screening for preventable adult-onset hereditary conditions may improve disease management and morbidity but most individuals will receive uninformative results that do not indicate higher risk for disease. Investigation into subsequent psychosocial health and behaviors is necessary to inform population screening feasibility, effectiveness, and cost considerations. We conducted a prospective survey study of unselected University of Washington Medicine patients enrolled in a genetic research study screening for pathogenic variation in medically important genes. Survey questions adapted from the Feelings About genomiC Testing Results (FACToR) questionnaire and designed to understand perceived disease risk change and planned health behaviors were administered after receipt of results. Overall, 2761 people received uninformative results and 1352 (49%) completed survey items. Respondents averaged 41 years old, 62% were female, and 56% were Non-Hispanic Asian. Results from the FACToR instrument showed mean (SD) scores of 0.92 (1.34), 7.63 (3.95), 1.65 (2.23), and 0.77 (1.50) for negative emotions, positive emotions, uncertainty, and privacy concerns, respectively, suggesting minimal psychosocial harms from genetic screening. Overall, 12.2% and 9.6% of survey respondents believed that their risk of cancer or heart disease, respectively, had changed after receiving their uninformative genetic screening results. Further, 8.5% of respondents planned to make healthcare changes and 9.1% other behavior changes. Future work is needed to assess observed behavior changes attributable to uninformative screening results and if small changes in behavior among this population have large downstream impacts.

Diagnostic yield of genetic screening in a diverse, community-ascertained cohort.

BACKGROUND: Population screening for genetic risk of adult-onset preventable conditions has been proposed as an attractive public health intervention. Screening unselected individuals can identify many individuals who will not be identified through current genetic testing guidelines. METHODS: We sought to evaluate enrollment in and diagnostic yield of population genetic screening in a resource-limited setting among a diverse population. We developed a low-cost, short-read next-generation sequencing panel of 25 genes that had 98.4% sensitivity and 99.98% specificity compared to diagnostic panels. We used email invitations to recruit a diverse cohort of patients in the University of Washington Medical Center system unselected for personal or family history of hereditary disease. Participants were sent a saliva collection kit in the mail with instructions on kit use and return. Results were returned using a secure online portal. Enrollment and diagnostic yield were assessed overall and across race and ethnicity groups. RESULTS: Overall, 40,857 people were invited and 2889 (7.1%) enrolled. Enrollment varied across race and ethnicity groups, with the lowest enrollment among African American individuals (3.3%) and the highest among Multiracial or Other Race individuals (13.0%). Of 2864 enrollees who received screening results, 106 actionable variants were identified in 103 individuals (3.6%). Of those who screened positive, 30.1% already knew about their results from prior genetic testing. The diagnostic yield was 74 new, actionable genetic findings (2.6%). The addition of more recently identified cancer risk genes increased the diagnostic yield of screening. CONCLUSIONS: Population screening can identify additional individuals that could benefit from prevention, but challenges in recruitment and sample collection will reduce actual enrollment and yield. These challenges should not be overlooked in intervention planning or in cost and benefit analysis.