Personal genome testing: Test characteristics to clarify the discourse on ethical, legal and societal issues

Abstract

BackgroundAs genetics technology proceeds, practices of genetic testing have become more heterogeneous: many different types of tests are finding their way to the public in different settings and for a variety of purposes. This diversification is relevant to the discourse on ethical, legal and societal issues (ELSI) surrounding genetic testing, which must evolve to encompass these differences. One important development is the rise of personal genome testing on the basis of genetic profiling: the testing of multiple genetic variants simultaneously for the prediction of common multifactorial diseases. Currently, an increasing number of companies are offering personal genome tests directly to consumers and are spurring ELSI-discussions, which stand in need of clarification. This paper presents a systematic approach to the ELSI-evaluation of personal genome testing for multifactorial diseases along the lines of its test characteristics.DiscussionThis paper addresses four test characteristics of personal genome testing: its being a non-targeted type of testing, its high analytical validity, low clinical validity and problematic clinical utility. These characteristics raise their own specific ELSI, for example: non-targeted genetic profiling poses serious problems for information provision and informed consent. Questions about the quantity and quality of the necessary information, as well as about moral responsibilities with regard to the provision of information are therefore becoming central themes within ELSI-discussions of personal genome testing. Further, the current low level of clinical validity of genetic profiles raises questions concerning societal risks and regulatory requirements, whereas simultaneously it causes traditional ELSI-issues of clinical genetics, such as psychological and health risks, discrimination, and stigmatization, to lose part of their relevance. Also, classic notions of clinical utility are challenged by the newer notion of 'personal utility.'SummaryConsideration of test characteristics is essential to any valuable discourse on the ELSI of personal genome testing for multifactorial diseases. Four key characteristics of the test - targeted/non-targeted testing, analytical validity, clinical validity and clinical utility - together determine the applicability and the relevance of ELSI to specific tests. The paper identifies and discusses four areas of interest for the ELSI-debate on personal genome testing: informational problems, risks, regulatory issues, and the notion of personal utility.

Advising patients about obtaining genomic profiles

“…11 This does not mean, however, that genomic information carries no clinical utility, but rather that its utility varies for different clinical decisions (table 2 for definitions of clinical utility, clinical validity, and analytic validity and their importance in determining whether genomic and genetic tests are ready for widespread clinical use). 12 For example, genomic profiling may soon play a larger role in untangling diagnostic dilemmas as cases accumulate in which identification by genomic sequencing of rare allelic variants leads to successful diagnosis …”

Genetic Profiling of Medical Students

“…Unlike clinical testing for a specific monogenetic disease, in this approach the tests typically result in profile information about the relative risk of developing a condition. The profile results are of limited clinical utility, particularly if they are interpreted without a correlation to a patient's overall health and medical history and if they yield a relative risk that is indistinguishable from that of the general population [1]. Consumers are not usually given in-depth, personalized preand posttest counseling or interpretation assistance as they would be when working with medical geneticists.…”

“…New gene-disease associations are being discovered continually, so a gene or sequence that is now thought to be inconsequential may in future be found to be diagnostic or predictive [1]. There is risk, therefore, that a student may ultimately be confronted with genetic information that he or she had not chosen to know.…”

“…In clinical genetics practices, extensive counseling provides patient with a solid foundation for making thoughtful and well-informed consent decisions [1]. In this case, this indepth counseling is unavailable and impractical.…”

Potential Uses and Inherent Challenges of Using Genome-Scale Sequencing to Augment Current Newborn Screening

“…These characteristics, combined with the complexity of genetic information, which ranges from probabilistic to highly deterministic, has led many to view genetic information as somehow different from other kinds of biomedical information ("genetic exceptionalism"). Consideration of the ethical, legal, and social implications of genetic knowledge has been an inherent component of the Human Genome Project and other genomic research efforts (Greely 1998), and inexorable advances in genetic testing have been accompanied by an immense societal discussion about the most appropriate uses of this information in healthcare, in human subjects research, and even in the setting of personal genomic exploration (Bunnik et al 2011). The thread of an individual's right to self-determination is woven tightly throughout the ethical considerations of genetic testing (e.g., Nyrhinen et al 2009;Bunnik et al 2013).…”