Return of genetic and genomic research findings: experience of a pediatric biorepository

Abstract

BackgroundAssess process, uptake, validity and resource needs for return of actionable research findings to biobank participants.MethodsParticipants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed.ResultsGenetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included.ConclusionsReturn of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.

Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy

“…Overall, our findings that high confidence variants identified using in silico prediction models have functional consequences validates our bioinformatics approach to novel variant discovery and makes a strong case for exploring variants in recurrently mutated cis-regulatory elements of CMP genes in order to increase the yield of genetic testing 80,81 . In summary, our work provides a guiding strategy to address regulatory variants in cardiac disease and emphasizes the need for further research to validate the clinical utility of these findings.…”

“…Ten cases (4.7%) died, and 130 cases (57%) experienced a major adverse cardiac event on follow-up ( Supplementary Table 1 ). Collection and use of human DNA and myocardial tissue from CMP cases through the Heart Centre Biobank Registry was approved by the Institutional Research Ethics Boards (Hospital for Sick Children, Children’s Hospital of Eastern Ontario, Toronto General Hospital, London Health Sciences Centre, Kingston General Hospital, and Hamilton Health Sciences Centre) and written informed consent was obtained from all patients and/or their parents / legal guardians 80,81 .…”

Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants

“…The key steps involved in the recontact and disclosure process included: (1) research sample validation; (2) recontact via US certified mail disclosing a DNA alteration that is potentially causing disease; (3) genetic counselor telephoned participants; (4) genetic counseling appointment; and (5) CLIA laboratory confirmatory genetic testing. Papaz et al [ 23 ] implemented a similar process among pediatric cardiovascular biobank participants (e.g., returning only actionable results, validating research samples prior to recontact). Our findings were comparable in regard to the uptake of genetic counseling (60%, 12/20 vs 55%, 11/20 reported here) and confirmatory genetic testing (100% 12/12 vs 91%, 10/11 reported here).…”

“…The average cost of those choosing to opt-in to genetic counseling and confirmatory genetic testing was $605. Other studies, including Papaz et al [ 23 ] and Christensen et al [ 9 ], reported an average cost of $750 and $679 per participant, respectively, to return clinically actionable research genetic results. This level of additional cost might lead some investigators to conclude that such an approach is not feasible.…”

A survey of aortic disease biorepository participants’ preferences for return of research genetic results

“…These cardiac studies have shown that cardiac populations-including early adopters of genetic testing (Facio et al, 2013) and individuals with heart disease (Joffe et al, 2019)are highly interested in broad results. In a feasibility return of result study of a pediatric biorepository of early-onset heart disease, 86% of families who received actionable findings opted to pursue clinical follow-up with clinical genetics (Papaz et al, 2019). The primary objective of this study was to determine a) whether and what type of results participants with aortic disease would like to receive, and b) participant preferences for how results should be returned.…”