of Improved Information

Mitigate Negative Reactions to Receiving Direct-To-Consumer Polygenic Risk Scores

Kyle Ma, Kennedy Borle, Jehannine Austin. Lasse Folkersen

Background: A polygenic risk score (PRS) estimates an individual’s genetic predisposition to a specific trait or condition by combining the estimated contribution or effect of a large number of known genetic variants, each contributing a small amount of risk. PRSs are increasingly available to people without the involvement of a healthcare provider, through commercial, direct-to-consumer genetic testing companies themselves, and from third-party services that allow users to upload raw genetic data to calculate PRSs for various complex conditions. A previous study found that over half of users (61%) who accessed direct to consumer PRSs experienced a negative reaction, and that this outcome was associated with lower understanding of PRSs.

Objective: To investigate whether improving the information provided about PRS reduces negative reactions experienced by users accessing PRSs without the involvement of healthcare provider through a not-for-profit third-party tool called Impute.me.

Methods: Data from a previous study about reactions to PRS among users of this website were used as baseline data. Specifically, to collect baseline data, individuals using Impute.me were invited to participate in an anonymous study in which they completed a questionnaire evaluating their reactions to PRS results using the Feelings About genomiC Testing Results (FACToR) questionnaire and the Impact of Event Scale–Revised (IES-R), understanding of the meaning of a PRS through five true/false questions, interpretation of a sample PRS result through three true/false questions, and questions about demographics and numeracy. Over 200 responses were collected in the baseline study after which it was closed.

Subsequently, the information about PRS that was provided to Impute.me users was enhanced through addition of a pie chart to visualize the portion of variability that can be explained by the PRS result, removal of complex information, and increasing digestibility of explanations to enhance readability. Individuals were again invited to participate in a study involving the same instruments as the baseline study. We conducted statistical tests (Chi Square and Mann Whitney-U) to assess differences in understanding and negative reactions before and after changes were made in how PRSs were communicated through Impute.me.

Results: 441 Impute.me users were recruited and completed the questionnaire. There were no significant changes in understanding of a PRS result (χχ2(1, n = 529) = 0.093, p = 0.415) or interpretation of a sample PRS result (χχ2(1, n = 492) = 0.422, p = 0.289). There were no significant changes in negative reactions to a PRS as measured by the FACToR scale (χ2(4, n = 481) = 0.422, p = 0.289) and the IES-R scale (U = 24593, p = 0.772), A significant relationship was found between lower understanding of a PRS result and experiencing a negative reaction measured by both the FACToR scale (U = 5133, p = 0.019) and IES-R scale (U = 4348, p = 0.02).

Conclusion: Our results indicate that improved information about PRS did not reduce negative reactions amongst impute.me users. There are several possible explanations for this finding: i) the improved information we provided was not sufficient in improving understanding, ii) the improved information we provided did improve understanding, but other variables contributed to experiencing a negative reaction, or iii) users did not read the information we provided to understand the implications of the PRS. For future studies, we suggest the creation and evaluation of a patient decision aid to support value-based decision making for users unsure if pursuing PRSs is the right decision for them and explore whether this mitigates negative reactions arising from the receipt of PRSs in this context.