TY - JOUR
T1 - Disclosing pleiotropic effects during genetic risk assessment for Alzheimer disease
AU - Christensen, Kurt D.
AU - Roberts, J. Scott
AU - Whitehouse, Peter J.
AU - Royal, Charmaine D.M.
AU - Obisesan, Thomas O.
AU - Cupples, L. Adrienne
AU - Vernarelli, Jacqueline A.
AU - Bhatt, Deepak L.
AU - Linnenbringer, Erin
AU - Butson, Melissa B.
AU - Fasaye, Grace Ann
AU - Uhlmann, Wendy R.
AU - Hiraki, Susan
AU - Wang, Na
AU - Cook-Deegan, Robert
AU - Green, Robert C.
N1 - Funding Information:
By grants HG002213, HG006500, HD077671, HG006993, AG013846, RR000533, RR010284, and TR001102 from the National Institutes of Health.
Publisher Copyright:
© 2016 American College of Physicians.
PY - 2016/2/2
Y1 - 2016/2/2
N2 - 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 APOEbased 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 APOEε4 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.
AB - 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 APOEbased 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 APOEε4 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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U2 - 10.7326/M15-0187
DO - 10.7326/M15-0187
M3 - Article
C2 - 26810768
AN - SCOPUS:84957641233
SN - 0003-4819
VL - 164
SP - 155
EP - 163
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 3
ER -