title: Known unknowns: building an ethics of uncertainty into genomic medicine.
abstract: Genomic testing has reached the point where, technically at least, it can be cheaper to undertake panel-, exome- or whole genome testing than it is to sequence a single gene. An attribute of these approaches is that information gleaned will often have uncertain significance. In addition to the challenges this presents for pre-test counseling and informed consent, a further consideration emerges over how - ethically - we should conceive of and respond to this uncertainty. To date, the ethical aspects of uncertainty in genomics have remained under-explored.
  
  
  
  In this paper, we draft a conceptual and ethical response to the question of how to conceive of and respond to uncertainty in genomic medicine. After introducing the problem, we articulate a concept of 'genomic uncertainty'. Drawing on this, together with exemplar clinical cases and related empirical literature, we then critique the presumption that uncertainty is always problematic and something to be avoided, or eradicated. We conclude by outlining an 'ethics of genomic uncertainty'; describing how we might handle uncertainty in genomic medicine. This involves fostering resilience, welfare, autonomy and solidarity.
  
  
  
  Uncertainty will be an inherent aspect of clinical practice in genomics for some time to come. Genomic testing should not be offered with the explicit aim to reduce uncertainty. Rather, uncertainty should be appraised, adapted to and communicated about as part of the process of offering and providing genomic information.
authors: Centre for Values, Ethics and the Law in Medicine, Sydney School of Public Health, University of Sydney, Level 1, Medical Foundation Building K25, 92-94, Parramatta Road, Camperdown, NSW, 2006, Australia. ainsley.newson@sydney.edu.au.
authors: Ainsley J
authors: AJ
authors: Newson
authors: Inserm, Unite 1027, University Toulouse III, Paul Sabatier, France.|Service de Genetique Medicale CHU Toulouse, Toulouse, France.
authors: Samantha J
authors: SJ
authors: Leonard
authors: PHG Foundation, Cambridge, UK.
authors: Alison
authors: A
authors: Hall
authors: Melbourne Genomics Health Alliance, Melbourne, Australia.|Departments of Paediatrics and Medicine, University of Melbourne, Melbourne, Australia.
authors: Clara L
authors: CL
authors: Gaff
mesh_terms: D004992:Ethics, Medical; D005260:Female; D005820:Genetic Testing / Q000941:ethics; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics; D035501:Uncertainty
keywords: Clinical genomics; Ethics; Genetic counseling; Genome sequencing; Genomic testing; Genomics; Massively parallel sequencing; Rare diseases; Uncertainty; Variants of uncertain significance