Viewing Direct-to-Consumer Genetic Test Results for Depression Risk Is Psychologically Well Tolerated: Evidence from a Longitudinal Equivalence Study

Background Depression is a frequent focus of interest in genetic testing. Despite growing availability of polygenic risk scores (PRS) for depression, little is known about the psychological impact of receiving them in real-world settings. To quantify the impact of receiving an at-risk depression PRS result on depression and anxiety symptoms, we conducted a longitudinal, prospective cohort study of 23andMe, Inc. research participants.

Surveys were conducted between October 19, 2022 and October 9, 2023. Eligible participants were U.S. residents ≥ 18 years old who completed two surveys assessing depression and anxiety symptoms and had an at-risk PRS result for depression (odds ratio ≥ 1.5). We compared individuals who viewed their result to individuals who did not. Primary outcomes were changes in depression (Patient Health Questionnaire-8) and anxiety (Depression Anxiety Stress Scale-21) symptom scores relative to baseline. We fitted linear regressions to model each outcome, adjusting for age, sex, genetic ancestry, income, prior depression and anxiety, and baseline scores. Using an equivalence testing framework, the smallest effect size of interest was defined as Cohen’s d = ±0.5. Findings We analyzed data from 917 participants, including 361 who viewed the depression PRS and 556 who did not. Score changes from baseline to follow-up were statistically equivalent for individuals who viewed PRS results and those who did not. The adjusted between-group differences in score changes were −0.17 points for depression (90% CI, −0.59–0.24, two one-side tests p < 0.001) and −0.092 points for anxiety (90% CI, −0.35–0.17, two one-side tests p < 0.001), both equivalent within the predefined margin. Results were consistent in substrata defined by presence or absence of prior depression or anxiety. Interpretation Among genetically at-risk individuals, exposure to a depression PRS result was well-tolerated in a real-world setting. Funding 23andMe, Inc. Competing Interest Statement At the time of their contributions, the following authors were employed by and held stock or stock options in 23andMe, Inc.: RMKB, DD, DC, CLR, JW, RRW, MVH, NSA-H. Funding Statement This study was funded by 23andMe, Inc. This study was conducted by current or former employees of 23andMe, Inc. 23andMe provided computing resources and the research platform used to host the surveys and collect participant data used in the study. The funding source had no role in the study design, data analysis, reporting, or submission of the manuscript for publication. The corresponding author affirms that all authors had full access to the data and accept responsibility for the decision to submit for publication. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: An external AAHRPP-accredited institutional review board, Salus IRB (ethics approval number 10044; https://www.versiticlinicaltrials.org/salusirb) gave ethnical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Individual-level data are not publicly available, due to participant privacy, and in accordance with the IRB-approved protocol under which the study was conducted.