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

Nandana D Rao; Jailanie Kaganovsky; Emily A Malouf; Sandy Coe; Jennifer Huey; Darwin Tsinajinne; Sajida Hassan; Kristine M King; Stephanie M Fullerton; Annie T Chen; Brian H Shirts

doi:10.1186/s13073-023-01174-7

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

Genome Med. 2023 Apr 18;15(1):26. doi: 10.1186/s13073-023-01174-7.

Authors

Affiliations

¹ Institute for Public Health Genetics, University of Washington, Seattle, WA, USA.
² Department of Laboratory Medicine and Pathology, University of Washington, Rm NW120, Box 357110 1959 NE Pacific Street, WA, 98195, Seattle, USA.
³ Department of Bioethics & Humanities, University of Washington School of Medicine, Seattle, WA, USA.
⁴ Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA.
⁵ Department of Laboratory Medicine and Pathology, University of Washington, Rm NW120, Box 357110 1959 NE Pacific Street, WA, 98195, Seattle, USA. shirtsb@uw.edu.
⁶ Brotman Baty Institute, Seattle, WA, USA. shirtsb@uw.edu.

Abstract

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.

Keywords: Diverse communities; Hereditary cancer; Hereditary hypercholesterolemia; Population genetic screening.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Black or African American
Ethnicity
Genetic Testing* / methods
Humans
Racial Groups*
Risk Factors