Disclosure of APOE genotype for risk of Alzheimer's disease

Robert C. Green, J. Scott Roberts, L. Adrienne Cupples, Norman R. Relkin, Peter J. Whitehouse, Tamsen Brown, Susan Larusse Eckert, Melissa Butson, A. Dessa Sadovnick, Kimberly A. Quaid, Clara Chen, Robert Cook-Deegan, Lindsay A. Farrer

Research output: Contribution to journalArticle

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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 timeaveraged 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 non-disclosure group and a disclosure subgroup of subjects carrying the APOE ε4 allele (which is associated with increased risk) also revealed no significant differences. However, the ε4-negative subgroup had a significantly lower level of test-related distress than did the ε4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the ε4-positive and ε4-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 ε4-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.)

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalNew England Journal of Medicine
Volume361
Issue number3
DOIs
StatePublished - Jul 16 2009
Externally publishedYes

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Disclosure
Apolipoproteins E
Alzheimer Disease
Genotype
Apolipoprotein E4
Anxiety
Depression
Psychology
Genetic Testing
Adult Children
Randomized Controlled Trials
Alleles

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Green, R. C., Roberts, J. S., Cupples, L. A., Relkin, N. R., Whitehouse, P. J., Brown, T., ... Farrer, L. A. (2009). Disclosure of APOE genotype for risk of Alzheimer's disease. New England Journal of Medicine, 361(3), 245-254. https://doi.org/10.1056/NEJMoa0809578

Disclosure of APOE genotype for risk of Alzheimer's disease. / Green, Robert C.; Roberts, J. Scott; Cupples, L. Adrienne; Relkin, Norman R.; Whitehouse, Peter J.; Brown, Tamsen; Eckert, Susan Larusse; Butson, Melissa; Sadovnick, A. Dessa; Quaid, Kimberly A.; Chen, Clara; Cook-Deegan, Robert; Farrer, Lindsay A.

In: New England Journal of Medicine, Vol. 361, No. 3, 16.07.2009, p. 245-254.

Research output: Contribution to journalArticle

Green, RC, Roberts, JS, Cupples, LA, Relkin, NR, Whitehouse, PJ, Brown, T, Eckert, SL, Butson, M, Sadovnick, AD, Quaid, KA, Chen, C, Cook-Deegan, R & Farrer, LA 2009, 'Disclosure of APOE genotype for risk of Alzheimer's disease', New England Journal of Medicine, vol. 361, no. 3, pp. 245-254. https://doi.org/10.1056/NEJMoa0809578
Green RC, Roberts JS, Cupples LA, Relkin NR, Whitehouse PJ, Brown T et al. Disclosure of APOE genotype for risk of Alzheimer's disease. New England Journal of Medicine. 2009 Jul 16;361(3):245-254. https://doi.org/10.1056/NEJMoa0809578
Green, Robert C. ; Roberts, J. Scott ; Cupples, L. Adrienne ; Relkin, Norman R. ; Whitehouse, Peter J. ; Brown, Tamsen ; Eckert, Susan Larusse ; Butson, Melissa ; Sadovnick, A. Dessa ; Quaid, Kimberly A. ; Chen, Clara ; Cook-Deegan, Robert ; Farrer, Lindsay A. / Disclosure of APOE genotype for risk of Alzheimer's disease. In: New England Journal of Medicine. 2009 ; Vol. 361, No. 3. pp. 245-254.
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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 timeaveraged 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 non-disclosure group and a disclosure subgroup of subjects carrying the APOE ε4 allele (which is associated with increased risk) also revealed no significant differences. However, the ε4-negative subgroup had a significantly lower level of test-related distress than did the ε4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the ε4-positive and ε4-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 ε4-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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AU - Brown, Tamsen

AU - Eckert, Susan Larusse

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