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. Methods 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 to 0.24, two one-side tests p < 0.001) and -0.092 points for anxiety (90% CI, -0.35 to 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.