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.
RCT Entities:
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.
Authors: Robert C Green; Kurt D Christensen; L Adrienne Cupples; Norman R Relkin; Peter J Whitehouse; Charmaine D M Royal; Thomas O Obisesan; Robert Cook-Deegan; Erin Linnenbringer; Melissa Barber Butson; Grace-Ann Fasaye; Elana Levinson; J Scott Roberts Journal: Alzheimers Dement Date: 2014-12-09 Impact factor: 21.566
Authors: Amy L McGuire; Steven Joffe; Barbara A Koenig; Barbara B Biesecker; Laurence B McCullough; Jennifer S Blumenthal-Barby; Timothy Caulfield; Sharon F Terry; Robert C Green Journal: Science Date: 2013-05-16 Impact factor: 47.728
Authors: Serena Chao; J Scott Roberts; Theresa M Marteau; Rebecca Silliman; L Adrienne Cupples; Robert C Green Journal: Alzheimer Dis Assoc Disord Date: 2008 Jan-Mar Impact factor: 2.703
Authors: Tari D Topolski; James LoGerfo; Donald L Patrick; Barbara Williams; Julie Walwick; Marsha B Patrick Journal: Prev Chronic Dis Date: 2006-09-15 Impact factor: 2.830
Authors: Yue Guan; Debra L Roter; Lori H Erby; Jennifer L Wolff; Laura N Gitlin; J Scott Roberts; Robert C Green; Kurt D Christensen Journal: Patient Educ Couns Date: 2016-12-14
Authors: Jason L Vassy; Sojeong Chun; Sanjay Advani; Sophie A Ludin; Jason G Smith; Elaine C Alligood Journal: Clin Pharmacol Ther Date: 2018-10-18 Impact factor: 6.875
Authors: Catharine Wang; Erynn S Gordon; Tricia Norkunas; Lisa Wawak; Ching-Ti Liu; Michael Winter; Rachel S Kasper; Michael F Christman; Robert C Green; Deborah J Bowen Journal: Obesity (Silver Spring) Date: 2016-12 Impact factor: 5.002
Authors: Jeffrey A Sparks; Maura D Iversen; Zhi Yu; Nellie A Triedman; Maria G Prado; Rachel Miller Kroouze; Sarah S Kalia; Michael L Atkinson; Elinor A Mody; Simon M Helfgott; Derrick J Todd; Paul F Dellaripa; Bonnie L Bermas; Karen H Costenbader; Kevin D Deane; Bing Lu; Robert C Green; Elizabeth W Karlson Journal: Arthritis Care Res (Hoboken) Date: 2018-04-16 Impact factor: 4.794
Authors: Richard H Carson; Charlotte R Lewis; Mercede N Erickson; Anna P Zagieboylo; Bradley C Naylor; Kelvin W Li; Paul B Farnsworth; John C Price Journal: J Lipid Res Date: 2017-07-25 Impact factor: 5.922
Authors: Talia S Schwartz; Kurt D Christensen; Melissa K Uveges; Susan E Waisbren; Amy L McGuire; Stacey Pereira; Jill O Robinson; Alan H Beggs; Robert C Green; Gloria A Bachmann; Arnold B Rabson; Ingrid A Holm Journal: J Genet Couns Date: 2021-07-26 Impact factor: 2.537