Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized, Controlled Trial.

Background: Increasing use of genetic testing raises questions about disclosing secondary findings, including pleiotropic information. Objective: To determine the safety and behavioral effect of disclosing modest associations between apolipoprotein E (APOE) genotype and coronary artery disease (CAD) risk during APOE-based genetic risk assessments for Alzheimer disease (AD). Design: Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov:NCT00462917) Setting: 4 teaching hospitals. Participants: 257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative. Intervention: Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only). Measurements: Primary outcomes were Beck Anxiety Inventory (BAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores at 12 months. Secondary outcomes were all measures at 6 weeks and 6 months and test-related distress and health behavior changes at 12 months. Results: At 12 months, mean BAI scores were 3.5 in both the AD-only and AD+CAD groups (difference, 0.0 [95% CI, -1.0 to 1.0]), and mean CES-D scores were 6.4 and 7.1 in the AD-only and AD+CAD groups, respectively (difference, 0.7 [CI, -1.0 to 2.4]). Both confidence bounds fell within the equivalence margin of +/- 5 points. Among carriers of the APOE epsilon 4 allele, distress was lower in the AD+CAD groups (difference, -4.8 [CI, -8.6 to -1.0]) (P = 0.031 for the interaction between group and APOE genotype). Participants in the AD+CAD groups also reported more health behavior changes, regardless of APOE genotype. Limitations: Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants. Conclusion: Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions. Providing risk modification information about CAD improved health behaviors. Findings highlight the potential benefits of disclosure of secondary genetic findings when options exist for decreasing risk.