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Cited by 554Dementia and Cognitive Impairment ResearchEthics in Clinical ResearchAlzheimer's disease research and treatments

Disclosure of APOE Genotype for Risk of Alzheimer's Disease

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Green, Robert C., Roberts, J. Scott, Cupples, L. Adrienne, Relkin, Norman R., Whitehouse, Peter J., Brown, Tamsen, Eckert, Susan LaRusse, Butson, Melissa +5 more·2009·New England Journal of Medicine
DOI 10.1056/nejmoa0809578PMC PMC2778270
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Abstract

BACKGROUND: The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial. METHODS: We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure. RESULTS: There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P=0.84), depression (8.8 and 8.7, respectively; P=0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the nondisclosure group and a disclosure subgroup of subjects carrying the APOE epsilon4 allele (which is associated with increased risk) also revealed no significant differences. However, the epsilon4-negative subgroup had a significantly lower level of test-related distress than did the epsilon4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the epsilon4-positive and epsilon4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons). CONCLUSIONS: The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE epsilon4-negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)

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  • ApoE genetic testing requires specific consent procedures and may raise ethical and psychological considerations.

    “Genetic testing requires specific consent procedures, may raise ethical and psychological considerations”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [15]

    The Methods (Study Design; page not provided) describe telephone and written informed consent and genetic counseling for this APOE study. The Methods (Safety Monitoring) and Discussion address ethical oversight and possible psychological harm. The paper does not establish that these specific consent procedures are required for genetic testing generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ApoE genetic testing is often associated with higher costs (typically hundreds of euros) compared with laboratory assays (less than a hundred euros in our setting).

    “is often associated with higher costs (typically in the order of hundreds of euros) and longer turnaround times (from several days to a few months) compared to laboratory assays that can provide results within hours and at substantially lower cost (less than a hundred euros in our setting) [13–15].”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [15]

    The Methods (Study Design; page unavailable) say that blood samples were sent to Athena Diagnostics for APOE genotyping, but give no price or turnaround time. Searches for costs and turnaround times found no passage comparing genotyping with laboratory assays or supporting the stated euro amounts. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • ApoE genetic testing is often associated with longer turnaround times (from several days to a few months) compared with laboratory assays that can provide results within hours.

    “longer turnaround times (from several days to a few months) compared to laboratory assays that can provide results within hours”

    From Plasma ApoE proteotyping for ApoE ε4 stratification in the anti-amyloid therapies era (2026) · cites this paper as [15]

    The Methods > Study Design passage says blood samples were sent for APOE genotyping, but gives no turnaround time. The Methods passages describe follow-up after disclosure, not how long testing took. Searches for turnaround time and the interval between sampling and disclosure found no comparison with laboratory assays that return results within hours. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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Cites

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Authors
Green, R. C., Roberts, J. S., Cupples, L. A., Relkin, N. R., Whitehouse, P. J., Brown, T., Eckert, S. L., Butson, M., Sadovnick, A. D., Quaid, K. A., Chen, C., Cook-Deegan, R., & Farrer, L. A.
Affiliations
  • Boston University (US)
  • University of Michigan (US)
  • Weill Cornell Medicine (US)
  • Case Western Reserve University (US)
  • University of British Columbia (CA)
  • Indiana University School of Medicine (US)
  • Duke University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2009-07-16
Volume
361
Issue
3
Pages
245-254
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa0809578
PMC
PMC2778270
OpenAlex
W1982813521
Cited by
554
References
3
Citations by year
2026: 27 · 2025: 28 · 2024: 18 · 2023: 8 · 2022: 19 · 2021: 29 · 2020: 77 · 2019: 22 · 2018: 28 · 2017: 28 · 2016: 29 · 2015: 35 · 2014: 33 · 2013: 40 · 2012: 37
FWCI
26.13
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Scholarly Commons @ Case Western Reserve University (submittedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • National Institutes of Health (5p50hg003391-09)
  • National Institute on Aging (R01-HG/AG-02213, K24AG027841, P30AG013846, R01AG009029)
  • National Human Genome Research Institute (P50-HG003391, R01HG002213)
  • National Center for Research Resources (M01RR000533)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Alzheimer's disease risk, apolipoprotein E, APOE ε4, genetic testing, psychological distress, anxiety, depression, asymptomatic adults, relatives of patients
MeSH terms
Adult, Aged, Alzheimer Disease, Anxiety, Depression, Female, Genetic Counseling, Genetic Testing, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Prospective Studies, Truth Disclosure, Chi-Square Distribution, Genetic Predisposition to Disease, Apolipoprotein E4

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