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

Abstract

There is ongoing debate on whether and what research genetic results to return to study participants. To date, no study in this area has focused on aortopathy populations despite known genes that are clinically actionable. Participants (n = 225, 79% male, mean age = 61 years) with an aortopathy were surveyed to assess preferences for receiving research genetic results. Participants were 'very' or 'extremely likely' to want results for pathogenic variants in aortopathy genes with implications for family members (81%) or that would change medical management (76%). Similarly, participants were 'very' or 'extremely likely' to want actionable secondary findings related to cancer (75%) or other cardiac diseases (70%). Significantly lower interest was observed for non-actionable findings-pathogenic variants in aortopathy genes that would not change medical management (51%) and variants of uncertain significance (38%) (p < .0001). Higher health and genomic literacy were positively associated with interest in actionable findings. Most participants (>63%) were accepting of any means of return; however, a substantial minority (18%-38%) deemed certain technological means unacceptable (e.g., patient portal). Over 90% of participants reported that a range of health professionals, including cardiovascular specialists, genetics specialists, and primary care providers, were acceptable to return results. Participants with aortopathies are highly interested in research genetic results perceived to be medically actionable for themselves or family members. Participants are accepting of a variety of means for returning results. Findings suggest that research participants should be asked what results are preferred at time of informed consent and that genetic counseling may clarify implications of results that are not personally medically actionable.

Trial registration: ClinicalTrials.gov NCT02306200.

Keywords: aortic disease; biobank; research genetic results; service delivery models; variants of uncertain significance.

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT:

Jamie Love-Nichols (jamie.love-nichols@childrens.harvard.edu) has no conflicts of interest to disclose.

Wendy Uhlmann (wuhlmann@med.umich.edu) has no conflicts of interest to disclose

Patricia Arscott (parscott@med.umich.edu) has no conflicts of interest to disclose

Cristen J. Willer (cristen@med.umich.edu) spouse works for Regeneron Pharmaceuticals, which has no relationship to this study.

Whitney E. Hornsby (whornsby@med.umich.edu) has no conflicts of interest to disclose.

J. Scott Roberts (jscottr@umich.edu) has no conflicts of interest to disclose

© 2020 National Society of Genetic Counselors.

Figures

Figure 1.

CONSORT study flow diagram. a Additional reasons include patient was overwhelmed (31), concerns about privacy (17), health limitations such as frailty (9). b 2 participants were excluded due to diagnoses of Hypermobile Ehlers Danlos Syndrome in absence of an aortic indication

Figure 2.

Participant responses to what types of results they would like returned (F (5, 1321) =31.48, p>>0.0001). The percentages along the y-axis represent likely and unlikely percentages of respondents to want results by scenario. The percentages in red boxes represent the percent “likely” and “extremely likely” to want each given type of results. A majority of participants wanted all types of results. Participants were significantly more likely to want actionable result categories (actionable aortic, secondary- heart, secondary-cancer, and primary results with family implications) than non-actionable results (VUS, non-actionable aortic). Brackets indicate significant differences assessed by one-way ANOVA with a Tukey HSD post-hoc test (*p

Figure 3.

A) Participant responses to how they would prefer these results be returned (F (4, 1076) =10.69, p>>0.0001). The percentages along the y-axes represent percent acceptable and unacceptable. Participants found in-person return to be the most acceptable form of result return and significantly preferred over email or phone call. There was no significant difference in acceptability between in-person appointment and letter. Brackets indicate significant differences assessed by one-way ANOVA with a Tukey HSD post-hoc test (*p