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

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 research participants. Eligible participants were U.S. residents ≥ 18 years old who completed two surveys between October 19, 2022 - October 9, 2023 assessing depression and anxiety symptoms, and who had an at-risk PRS for depression (odds ratio ≥ 1.5). We compared 361 individuals who viewed their result to 556 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, ancestry, income, prior depression and/or anxiety, and baseline scores. Using an equivalence testing framework, the smallest effect size of interest was defined as Cohen's d = ±0.5. Score changes from baseline to follow-up were statistically equivalent for individuals who viewed results and those who did not (adjusted between-group differences in score changes: depression, -0.17 points [90% CI -0.59-0.24]; anxiety, -0.092 points [90% CI -0.35-0.17]; all p < 0.001). Results were consistent in substrata with or without prior depression or anxiety. We conclude that among genetically at-risk individuals, exposure to a depression PRS result was well-tolerated in a real-world setting.