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Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial
Christensen KD, Roberts JS, Whitehouse PJ, Royal CD, Obisesan TO, Cupples LA, Vernarelli JA, Bhatt DL et al.. Annals of internal medicine, 2016-01-26
Topic: Amyloid, tau and blood-test diagnosis
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.
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APA 7th
Christensen, K. D., Roberts, J. S., Whitehouse, P. J., Royal, C. D., Obisesan, T. O., Cupples, L. A., et al. (2016). Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial. Annals of internal medicine. https://doi.org/10.7326/m15-0187
Vancouver
Christensen KD, Roberts JS, Whitehouse PJ, Royal CD, Obisesan TO, Cupples LA, et al. Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial. Annals of internal medicine. 2016. doi:10.7326/m15-0187. PMID: 26810768.
BibTeX
@article{christensen2016-26810768,
author = {Christensen, K. D. and Roberts, J. S. and Whitehouse, P. J. and Royal, C. D. and Obisesan, T. O. and Cupples, L. A. and Vernarelli, J. A. and Bhatt, D. L. and others},
title = {{Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial}},
journal = {Annals of internal medicine},
year = {2016},
doi = {10.7326/m15-0187},
pmid = {26810768},
url = {https://doi.org/10.7326/m15-0187}
}
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Key findings
- 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]).
- Conclusion Disclosure of pleiotropic information did not increase anxiety or depression and may have decreased distress among persons at increased risk for 2 conditions.
Why it matters
This trial found that disclosing genetic risk information about both Alzheimer's disease and coronary artery disease did not increase anxiety or depression compared with disclosing Alzheimer's risk alone. This concerns how genetic risk information is shared, not treating, curing, or preventing Alzheimer's disease.
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Study details
- Evidence strengthHigh
How this study scored 65/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 62 of the 96 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of internal medicine) |
| Journal's citation record | 4 / 4 | Annals of Internal Medicine: journal h-index 648 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 4 / 7 | Cited 45 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 3 / 6 | Cited 6.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | University of Michigan: institution h-index 2,240 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26810768) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 62 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 62 of the 96 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
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