0The Question Not Asked: The Challenge of Pleiotropic Genetic Tests

Abstract

Nearly all of the literature on the ethical, legal, or social issues surrounding genetic tests has proceeded on the assumption that any particular test for a gene mutation yields information about only one disease condition. Even though the phenomenon of pleiotropy, where a single gene has multiple, apparently unrelated phenotypic effects, is widely recognized in genetics, it has not had much significance for genetic testing until recently. In this article, I examine a moral dilemma created by one sort of pleiotropic testing, APOE genotyping, which can yield information about the risk of two different conditions--coronary heart disease and Alzheimer's disease. A physician administering APOE testing for the beneficial purpose of assessing the risk of heart disease may discover medically useless and socially harmful information about the patient's risk of Alzheimer's disease. I explore how much providers should disclose to patients about pleiotropic test results and whether patients are obligated to know as much about their genetic condition as possible.

To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts

“…The full texts of the resulting 35 articles were read, and eventually 13 articles were accepted for systematic review (Figure 1). Of these 13, 9 came from the original electronic databases searches, 3,8,12,[16][17][18][19][20][21] 4 from the 'snowballing method' , 11,13,22,23 and none from electronic updates between December 2010 and September 2011 from Pubmed and Web of Science.…”

“…The four articles dealing with clinical care do not mention it, giving only arguments against disclosure or offering caution. 3,11,16,20 Some define clinical utility both in terms of what a medical professional would judge to be important clinically and what a research participant would judge to be important in terms of health or reproductive information. 17 In certain circumstances, confirmed clinical utility is an argument strong enough to outweigh a stated preference for non-disclosure.…”

“…17 In addition, another cluster of arguments emphasize that what is at issue is net benefit: authors writing in a clinical setting argue that if the accompanying anxiety and possible discrimination and stigmatization from the point of view of the patient are perceived as greater than the potential clinical utility, this can argue against disclosure. 3,11 An example is the IF that someone is at heightened risk of developing Alzheimer's disease. 3 Furthermore, the potential but unlikely benefits accruing from disclosing an IF that is not so serious, untreatable, and/ or of uncertain significance may be so small that, in a research setting, it is better to respect the subject's right not to know and not disclose.…”

“…3,11 An example is the IF that someone is at heightened risk of developing Alzheimer's disease. 3 Furthermore, the potential but unlikely benefits accruing from disclosing an IF that is not so serious, untreatable, and/ or of uncertain significance may be so small that, in a research setting, it is better to respect the subject's right not to know and not disclose. 12 Unlikely net benefit is a particular concern when minors are involved.…”

“…1 Examples include a brain aneurysm in a healthy control subject involved in neuroimaging research, 1 a malignant skin tumor discovered during a woman's routine breast cancer screening, 2 and learning that someone is of higher risk of Alzheimer's disease when they present at a genetics clinic wanting to know if there is a genetic cause for their cardiac condition. 3 IFs have been defined as findings having potential health or reproductive importance for an individual, discovered in the course of conducting a particular study (in research, clinical care or screening) but beyond the aims of that study. 1 In recent years, much has been published on IFs in general and IFs arising in imaging contexts.…”