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 the growing availability of polygenic risk scores (PRSs) 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 US residents 18 years old and older who completed two surveys between October 19, 2022 and 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 with 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% confidence interval {CI} -0.59 to 0.24]; anxiety, -0.092 points [90% CI -0.35 to 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.