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Ann Intern Med. 2016 Feb 2;164(3):155-63. doi: 10.7326/M15-0187. Epub 2016 Jan 26.

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

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.

PMID:
26810768
PMCID:
PMC4979546
DOI:
10.7326/M15-0187
[Indexed for MEDLINE]
Free PMC Article

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