Disclosure of Genetic Variants of Uncertain Significance Results in an Exome Cohort

Genetic result disclosure;Variant of Uncertain Significance;Decision-making;Exome sequencing;Decision regret;Nursing

Lawal, Tokunbor AyodeleSzanton, Sarah L. ;

Johns Hopkins University

关键词: Genetic result disclosure;    Variant of Uncertain Significance;    Decision-making;    Exome sequencing;    Decision regret;    Nursing;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/59315/LAWAL-DISSERTATION-2017.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Background: The emergence of next generation sequencing as a clinical tool in aiding diagnosis is fueling enthusiasm to provide genomic information to patients. One consequence of this technology is that genetic results are more likely to include variants of uncertain significance (VUS). VUS are alterations in the DNA sequence of a gene that have an intermediate probability of pathogenicity or disease risk. There are no universally accepted standards for reporting VUS results. Also, conveying the potential implications of uncertain results to patients and research participants sufficiently to inform their decision-making is challenging. Uncertainty can have a variety of psychological effects. Perceptions related to uncertainty are likely to predict decisions to learn genetic results and to act on the information. There is a need to examine the impact of the inherent uncertainty in genetic sequencing information on the perceptions of recipients. However, most reports in the literature involve hypothetical studies of VUS disclosures. Objectives: a) To describe the effect of perceived risk and perceived severity associated with disclosure of genetic variants of uncertain significance results on health behavior intentions, b) to describe the effect of perceived value of information and self-efficacy associated with disclosure of genetic variants of uncertain significance results on health behavior intentions, c) to examine the influence of resilience, optimism, and tolerance of uncertainty on health behavior intentions post disclosure of genetic variants of uncertain significance results, and d) to measure the level of regret associated with decision to learn genetic variants of uncertain significance results 2 weeks post disclosure. iii Design and Methods: A predictive correlational design was employed. Survey responses were collected 2 weeks following disclosure of results. Correlation analysis and multiple linear regressions were used to examine the relationships of interest in the first three aims, while descriptive statistics was used for the fourth aim. Sample: Eighty-one participants with exome-generated variants of uncertain significance (VUS) in one of 20 cardiomyopathy-associated genes from the ClinSeq;; study participated in the study. Findings: Most participants (79%) intended to seek more information about their result in the future, over 80% intended to share their result with family members and health-care providers, and 46% intended to use result to change their lifestyle and health behaviors. Perceived risk, perceived severity, perceived value of information, self-efficacy, and sex explained 42.5% (Adjusted R^2 = 38.6%) of the variance in health behavior intentions of recipients of VUS results. Perceived value of information was the strongest predictor of health behavior intentions (β = 0.529, p < 0.001). Behavior intentions was moderately correlated with optimism (r =0.25, p = 0.03), and weakly correlated with resilience (r=0.11, p = 0.614) and tolerance of uncertainty (r= -0.05, p = 0.669). The mean decision regret score was 12.41 (SD=16.42) on a 0 to 100 scale (score of 0 = no regret). Thirty-five participants (51.5%) reported no regret (0/100) associated with their decision, and 57 (83.8%) reported a score of 30/100 or less. Conclusions: Our findings suggest that perceived benefits associated with receipt of uncertain genetic information are more likely to motivate recipients to pursue health related behaviors than discussions of possible risk and severity associated with results. Despite the ambiguity iv associated with genetic variants of uncertain significance, there is minimal regret regarding a decision to learn these results.