In sickness and in health: context matters when considering potential benefits and risks of genome-wide sequencing

Journal name:
Genetics in Medicine

To the Editor: A recent op-ed piece in the Los Angeles Times characterized whole-genome sequencing (WGS) as “an absurd medical test.”1 The article focused on the deficiencies of WGS in identifying useful disease-risk associations, arguing that associations that are actionable are already identifiable through observed family history, and that beyond these “low hanging fruit” WGS is likely to do more harm than good.

Caution regarding the overstatement of benefits is warranted. However, the type of characterization of WGS offered in this article does a disservice to those for whom WGS is already useful. Broad statements proclaiming harm are similarly problematic to those of promise; such simplistic messages are misleading. The type of cautions (and potential benefits) directly relevant for a seemingly healthy person are likely different—or at least weighted differently—than for someone considering sequencing in the context of an undiagnosed disease or life-threatening illness. Context matters a lot when considering the potential risks and benefits of genome sequencing. Failure to account for the salience of context itself has far-reaching potential for harm.

Considerations regarding whether to pursue technologies, interventions, and treatment options are inherently context-dependent throughout medicine. Genome-wide sequencing is not any different in that regard. Ethical and legal experts commonly cite implications for long-term care and disability insurance as a significant risk of undergoing WGS or other types of next-generation sequencing. For a person diagnosed with a life-threatening illness, however, this risk has already been realized independent of testing. To forgo potentially beneficial therapy information in order to avoid this contextually irrelevant risk would be imprudent. Similarly, concerns related to potential psychosocial harms derived from learning about worrisome predispositional genes may no longer carry much weight for a person already experiencing an actual life-threatening illness.

The authors of the op-ed piece seem to focus on the use of WGS for preventive screening purposes and note the potential for misinterpretation of such results. For example, they specifically cite the irrelevance of a small increase in risk for health management or other interventions, which could result in unnecessary worry. This, however, is hardly the only use of WGS at this time. Nonscreening uses of WGS have already shown far more concrete applicability such as when genome-wide sequencing is proposed to end a diagnostic odyssey or guide chemotherapy. In these cases, testing has been done not to “predict the future” but rather to provide an actual diagnosis2,3 or data to inform therapy best suited to an individual.4

Delineating the different contextual risks and benefits of WGS will take time and requires empirical exploration. One seemingly obvious but often neglected differentiation is the starting point for individuals (or family members), whether they are “sick” or “healthy.” Decision making in the context of illness likely influences the weightings given to risks and benefits—perhaps even reframing the balance of promise and concern entirely (a “game changer”). The authors were correct that for “most people” at this time, it does seem an absurd test. Any medical test would be absurd for most (healthy) people at any given time. But for those who benefit from the early days of a newer technology, the absurd becomes transformative.


The authors declare no conflict of interest.


  1. Welch HG, Burke W. Op-Ed: why whole-genome testing hurts more than it helps. Los Angeles Times 27 April 2015.
  2. Tifft CJ, Adams DR. The National Institutes of Health undiagnosed diseases program. Curr Opin Pediatr 2014;26:626633.
  3. Worthey EA, Mayer AN, Syverson GD, et al. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet Med 2011;13:255262.
  4. MacConaill LE. Existing and emerging technologies for tumor genomic profiling. J Clin Oncol 2013;31:18151824.

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The participation of K.A.S. and T.M. in this article was supported by the Advancing a Healthier Wisconsin Research and Education Program Fund, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin.

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  1. Program in Genomics and Ethics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    • Kimberly A. Strong &
    • Thomas May
  2. Hudson Alpha Institute for Biotechnology, Huntsville, Alabama, USA

    • Shawn A. Levy

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