Mapping uncertainty in genomics

The relatively novel and dynamic science of genomics holds many unknowns for stakeholders, and in particular for researchers and clinicians, as well as for participants and patients. At a time when many authors predict a future in which genomic medicine will be the norm, it is particularly relevant to discuss the unknowns surrounding genetics and genomics, including the notions of risk and uncertainty. This article will present a discussion regarding the uncertainty pertaining specifically to high throughput sequencing approaches, including the topic of incidental findings. This discussion will be guided by a taxonomy of uncertainty conceptualised around three areas of uncertainty: the source of uncertainty, the issues of uncertainty and the loci of uncertainty. This taxonomy can be used as a tool by all stakeholders involved in genomics to help further understand and anticipate uncertainties in genomics. Furthermore, to better contextualize this information, and also because this contribution is born out of an international project titled ‘Mind the Risk’, which addresses risk information in genetics and genomics from many different disciplinary perspectives, another aim of this article is to briefly present the basic issues pertaining to the unknowns, risks, and uncertainties of genetics as well as genomics for an audience of non-geneticists. Ultimately, the mapping out of uncertainty in genomics should allow for a better characterization of the uncertainty and consequently for a better management and communication of these uncertainties to end-users (research participants and patients).

[1]  A. McGuire,et al.  Informed consent in genomics and genetic research. , 2010, Annual review of genomics and human genetics.

[2]  C R Scriver,et al.  Monogenic traits are not simple: lessons from phenylketonuria. , 1999, Trends in genetics : TIG.

[3]  Sandi Dheensa,et al.  Defining and managing incidental findings in genetic and genomic practice , 2014, Journal of Medical Genetics.

[4]  M. Bamshad,et al.  Genomics really gets personal: How exome and whole genome sequencing challenge the ethical framework of human genetics research , 2011, American journal of medical genetics. Part A.

[5]  H. Howard,et al.  Ethical issues raised by whole genome sequencing. , 2014, Best practice & research. Clinical gastroenterology.

[6]  Marc S. Williams,et al.  ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing , 2013, Genetics in Medicine.

[7]  Rena A. Godfrey,et al.  The implications of familial incidental findings from exome sequencing: The NIH Undiagnosed Diseases Program experience , 2014, Genetics in Medicine.

[8]  Ortwin Renn,et al.  A New Approach to Risk Evaluation and Management: Risk‐Based, Precaution‐Based, and Discourse‐Based Strategies 1 , 2002, Risk analysis : an official publication of the Society for Risk Analysis.

[9]  Christian Gilissen,et al.  Disease gene identification strategies for exome sequencing , 2012, European Journal of Human Genetics.

[10]  Paul K J Han,et al.  Varieties of uncertainty in health care: a conceptual taxonomy. , 2011, Medical decision making : an international journal of the Society for Medical Decision Making.

[11]  A. Cambon-Thomsen,et al.  The Ethical Introduction of Genome-Based Information and Technologies into Public Health , 2013, Public Health Genomics.

[12]  Paul K. J. Han,et al.  Varieties of Uncertainty in Health Care , 2011 .

[13]  W. Klein,et al.  How do research participants perceive “uncertainty” in genomic sequencing? , 2014, Genetics in Medicine.

[14]  Jorge Sequeiros,et al.  Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing , 2009, European Journal of Human Genetics.

[15]  Emily H Turner,et al.  Actionable, pathogenic incidental findings in 1,000 participants' exomes. , 2013, American journal of human genetics.

[16]  J. Roberts,et al.  Genetic susceptibility testing for neurodegenerative diseases: Ethical and practice issues , 2013, Progress in Neurobiology.

[17]  P. Baptista.  Principles in genetic risk assessment , 2005, Therapeutics and clinical risk management.

[18]  J. Millán,et al.  Informed consent for whole-genome sequencing studies in the clinical setting. Proposed recommendations on essential content and process , 2013, European Journal of Human Genetics.

[19]  J. Bell.  Predicting disease using genomics , 2004, Nature.

[20]  So rare we need to hunt for them: reframing the ethical debate on incidental findings , 2015, Genome Medicine.

[21]  B. Solomon.  Obstacles and opportunities for the future of genomic medicine , 2014, Molecular genetics & genomic medicine.

[22]  A M Kellerer,et al.  Risk perception , 1993, Nature.

[23]  Paul K J Han,et al.  Conceptual, Methodological, and Ethical Problems in Communicating Uncertainty in Clinical Evidence , 2013, Medical care research and review : MCRR.