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P1‐215: Grading the Credibility of Genetic Associations in Alzheimer's Disease Using the Interim Venice Criteria
Author(s) -
Broer Linda,
Schuur Maaike,
Janssens A. Cecile,
Duijn Cornelia
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.494
Subject(s) - credibility , interim , econometrics , grading (engineering) , robustness (evolution) , statistics , type i and type ii errors , medicine , computer science , psychology , mathematics , genetics , gene , biology , political science , ecology , law
persons receiving negative genetic test results inappropriately under-estimate their disease risk. Few studies have examined this empirically. We utilized self-reported risk for Alzheimer’s disease (AD) to see if false reassurance could be observed in cognitively normal individuals following genetic risk assessment. Methods:The REVEALStudy is a series of multisite randomized controlled trials assessing the impact of Apolipoprotein E (APOE) disclosure and genetic risk assessment for AD. This analysis used 6-week post-disclosure data from participants in the second and third REVEAL trials with a family history of AD (n 1⁄4 434; mean age 58.2yrs610.8;66% female; 16% African American). We tested whether those who learned that they were e4-were more likely to underestimate their actual AD risk compared to those who learned that they were e4+ using logistic regression and controlling for age, gender, education, number of affected relatives and REVEAL trial. Since all participants had a first degree relative with AD, and since all educational materials in the study stressed the importance of heritable risk regardless of APOE genotype, false reassurance was defined as occurring in participants who reported a perceived risk that was lower, or equal, to someone who did not have a family history of AD (eg. 10-15% lifetime risk of AD). Results: Twenty-six percent of participants underestimated their risk of developing AD (defined above). Participants who were e4(37%) had greater odds of underestimating their AD risk compared to e4+ participants (10%) (OR1⁄4 5.17, 95% CI: 2.84-9.41, p < 0.001). Participants who were younger than 60 years or who were African American also showed a risk underestimation (OR 1⁄4 2.81,95% CI: 1.72-4.56, p < 0.001 and OR 1⁄4 2.70, 95% CI: 1.44-5.04, p1⁄4 0.002, respectively). Conclusions: These results demonstrate that false reassurance occurs following genetic susceptibility testing for AD among individuals who learn that they are APOE e4-. As researchers begin stratifying AD intervention trials by including genetic testing and clinicians begin using genetic testing for risk estimation, they should be aware that false reassurance among individuals who learn negative genetic test results may make them less likely to participate in research trials, behavior modifications or other interventions.