title: Disclosing Pleiotropic Effects During Genetic Risk Assessment for Alzheimer Disease: A Randomized Trial.
abstract: 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).
  
  
  METHODS
  Randomized, multicenter equivalence clinical trial. (ClinicalTrials.gov: NCT00462917).
  
  
  METHODS
  4 teaching hospitals.
  
  
  METHODS
  257 asymptomatic adults were enrolled, 69% of whom had 1 AD-affected first-degree relative.
  
  
  METHODS
  Disclosure of genetic risk information about AD and CAD (AD+CAD) or AD only (AD-only).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Outcomes were self-reported by volunteers without severe anxiety, severe depression, or cognitive problems. Analyses omitted 33 randomly assigned participants.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  National Human Genome Research Institute.
authors.forename: Kurt D
authors.initials: KD
authors.lastname: Christensen
authors.forename: J Scott
authors.initials: JS
authors.lastname: Roberts
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Whitehouse
authors.forename: Charmaine D M
authors.initials: CD
authors.lastname: Royal
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Obisesan
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Vernarelli
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Erin
authors.initials: E
authors.lastname: Linnenbringer
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Butson
authors.forename: Grace-Ann
authors.initials: GA
authors.lastname: Fasaye
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Uhlmann
authors.forename: Susan
authors.initials: S
authors.lastname: Hiraki
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Cook-Deegan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000523:psychology; D001007:Anxiety / Q000209:etiology; D053327:Apolipoprotein E4 / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics* / Q000523:psychology; D003863:Depression / Q000209:etiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015438:Health Behavior; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D013315:Stress, Psychological / Q000209:etiology; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4
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