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Opportunistic Genomic Screening: How much do we really want to know?

When an individual undergoes genomic screening, the opportunity arises to further review their genomic data in the future. This is known as Opportunistic Genomic Screening (OGS). In 2013, the European Society of Human Genetics (ESHG) recommended that genome analysis should be limited to the original health problem. However, other organisations have argued that ‘actionable’ genetic variants outside of the original health problem should or could be reported.

A paper, published in Nature, explores the risks, benefits and ethical landscape of opportunistic genomic sequencing and the current recommendations of the ESHG

Opportunistic Genomic Screening

In the near future, it is likely that individuals who require genetic testing may have their exome, or now increasingly, their entire genome sequenced. Genome sequencing allows targeted bioinformatics analysis of sequence data. This process targets genes which are most likely to be associated with the symptoms presented by an individual. 

However, during such a targeted analysis, unsolicited, incidental findings may emerge, unrelated to the primary reason for genome sequencing. Debate is ongoing about the pros and cons of expanding analysis through actively looking for additional variants. These could be relevant to the health prospects and/or reproductive choices of the patient or their family. Such medically ‘actionable’ secondary findings could allow disease prevention, facilitate the early management of a disease, or inform reproductive decisions.

However, for this process to evolve, informed consent must become an ethical norm. Furthermore a cautious approach is required, only informing individuals of ‘actionable’ genetic variants to prevent undue stress.

Potential Benefits of Opportunistic Genome Screening

The possible benefits of OGS are primarily medical. OGS provides information which could allow the prevention or early intervention of serious genetic diseases. These health benefits primarily depend on the effectiveness of existing preventative interventions. Measures that are recommended to these individuals should be scientifically proven, and access to these interventions must be guaranteed.

OGS can also screen for variants which may cause serious adverse reactions to therapeutics or medications. Knowledge of these variants may allow for a more favourable risk-benefit ratio of medical interventions. In addition to health benefits, OGS may provide reproductive benefits, allowing the persons being screened or their relatives to make informed reproductive decisions.

Potential Risks

OGS comes with a range of psychological, social and medical risks. In the absence of sufficient evidence regarding the health impact of genetic variants, OGS data may overestimate the risk of actually developing a disorder. This overestimation may lead to unnecessary anxiety and/or the subjection of individuals to unpleasant or invasive diagnostic or preventative measures. This misclassification of variants is especially common in ethnically diverse populations.

To avoid this psychological burden, only ‘actionable’ conditions should be reported and potential interventions must be highly promising. Counselling should also be provided and OGS should be offered in a way that empowers people, rather than undermining their confidence in their health.

Respect for Autonomy

Patients who want to undergo genomic screening without their data being searched for secondary findings can opt out of OGS if they wish. However, this option is limited by patient understanding of OGS. An adequate procedure of informed consent will be required to minimise these issues as much as possible.

Cost of Opportunist Genomic Screening

The cost of bioinformatics analysis and confirmation of detected variants remains high, despite advances in machine-learning based procedures. Furthermore, genetic counselling costs may be considerable, given the need to repeatedly counsel individuals as new evidence is discovered. These downstream costs for the healthcare system are not problematic, but stress the need to only offer OGS for variants with a proven health impact, to avoid the cost of unnecessary interventions and overdiagnosis.

Concluding Remarks

If a practitioner initiates OGS procedures, they should have conclusive evidence that screening could alter the natural history of disease in a significant proportion of those screened. Therefore, both evidence that screening is favourable and explicit informed consent from the individual is required.

Genomic analysis should be as targeted as possible. If OGS is offered, it should undergo rigorous evaluation to determine its proportionality as a healthcare service. Finally, the ESHG stresses that given the rapid developments in this field and the likely need for further reflection, these recommendations will require regular evaluation in the future.

More on these topics

Ethics / Personalised Health / Prevention / WGS