Abstract
BackgroundDisclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented. The impact and costs, including confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, were evaluated.MethodsWe exome sequenced 240 cases with thoracic aortic dissection and 258 controls, then examined 11 aortopathy genes. Pathogenic variants in 6 aortopathy genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, and TGFBR2) were identified in 26 participants, representing 10.8% of the cohort (26/240). A second research sample was used to validate the initial findings. Mailed letters to participants disclosed that a potentially disease causing DNA alteration had been identified (neither the gene nor variant was disclosed). Participants were offered clinical genetic counseling and confirmatory genetic testing in a CLIA laboratory.ResultsExcluding 6 participants who were deceased or lost to follow-up, 20 participants received the disclosure letter, 10 of whom proceeded with genetic counseling, confirmatory genetic testing, and enrolled in a survey study. Participants reported satisfaction with the letter (4.2 ± 0.7) and genetic counseling (4.4 ± 0.4; [out of 5, respectively]). The psychosocial impact was characterized by low decisional regret (11.5 ± 11.6) and distress (16.0 ± 4.2, [out of 100, respectively]). The average cost for 26 participants was $400, including validation and sending letters. The average cost for those who received genetic counseling and CLIA laboratory confirmation was $605.ConclusionsParticipants were satisfied with the return of clinically significant biobank genetic results and CLIA laboratory testing; however, the process required significant time and resources. These findings illustrate the trade-offs involved for researchers considering returning research genetic results.
Highlights
Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented
In situations where research genetic results are clinically actionable, researchers may feel an ethical obligation or that it is helpful to the participant to disclose this information [6]
Of 26 participants with pathogenic variants, three participants were known from Electronic Health Record (EHR) to be deceased prior to mailing letters, and 23 letters were mailed
Summary
Disclosure of pathogenic variants to thoracic aortic dissection biobank participants was implemented. The impact and costs, including confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, were evaluated. Genetic research studies generate individual results that may have clinical implications for participants, but these findings require confirmatory genetic testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory prior to use in clinical care [1, 2]. In 2019, the American Society of Human Genetics released a position statement on investigators’ responsibility to recontact research participants, especially if a clinically actionable variant is identified [5]. In situations where research genetic results are clinically actionable, researchers may feel an ethical obligation or that it is helpful to the participant to disclose this information [6]
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