Publications [#316124] of Charmaine D. Royal

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  1. Christensen, KD; Roberts, JS; Whitehouse, PJ; Royal, CDM; Obisesan, TO; Cupples, LA; Vernarelli, JA; Bhatt, DL; Linnenbringer, E; Butson, MB; Fasaye, G-A; Uhlmann, WR; Hiraki, S; Wang, N; Cook-Deegan, R; Green, RC; REVEAL Study Group*, , Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial., Annals of internal medicine, vol. 164 no. 3 (February, 2016), pp. 155-163 [doi] .
    (last updated on 2024/08/25)

    Abstract:

    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 ε4 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.

    Primary funding source

    National Human Genome Research Institute.