Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Proprietary Algorithms for Polygenic Risk: Protecting Scientific Innovation or Hiding the Lack of It?

Version 1 : Received: 22 May 2019 / Approved: 23 May 2019 / Online: 23 May 2019 (16:23:57 CEST)

A peer-reviewed article of this Preprint also exists.

Janssens, A.C.J.W. Proprietary Algorithms for Polygenic Risk: Protecting Scientific Innovation or Hiding the Lack of It? Genes 2019, 10, 448, doi:10.3390/genes10060448. Janssens, A.C.J.W. Proprietary Algorithms for Polygenic Risk: Protecting Scientific Innovation or Hiding the Lack of It? Genes 2019, 10, 448, doi:10.3390/genes10060448.

Abstract

Direct-to-consumer genetic testing companies aim to predict the risks of complex diseases using proprietary algorithms. Companies keep algorithms as trade secrets for competitive advantage, but a market that thrives on the premise that customers can make their own decisions about genetic testing should respect customer autonomy and informed decision making and maximize opportunities for transparency. The algorithm itself is only one piece of the information that is deemed essential for understanding how prediction algorithms are developed and evaluated. Companies should be encouraged to disclose everything else, including the expected risk distribution of the algorithm when applied in the population, using a benchmark DNA dataset. A standardized presentation of information and risk distributions allows customers to compare test offers and scientists to verify whether the undisclosed algorithms could be valid. A new model of oversight in which stakeholders collaboratively keep a check on the commercial market is needed.

Keywords

personal genomics, DNA, polygenic, risk, regulation, discrimination, calibration, prediction, transparency, autonomy

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Comments (1)

Comment 1
Received: 31 May 2019
Commenter: David Curtis
The commenter has declared there is no conflict of interests.
Comment: Thanks for this.

I would like to see more about recommendations for the way risk is communicated to the customer. For example, a company may just say that a PRS indicates the subject is at "increased risk" or "high risk", or "in the top 20% of risk". I believe such statements are highly misleading. Typically, the risk only changes to any appreciable extent at the very extreme PRS values. Almost everybody is in the middle and has about average risk.

The absolute risk should be communicated, not the relative risk (which is easier, in terms of an odds ratio). Again, telling somebody that their cancer risk is doubled will be misinterpreted if the background risk was only 0.0005 to start with. And obviously one should not make statements such as "risk is increased by 10%" if one means the risk changes from 0.01 to 0.011 when this is likely to be interpreted as a change from 0.01 to 0.11.

Ideally, one should communicate an absolute risk specific to the subject, alongside what the risk estimate would have been without the genetic information. "Given your test results, we estimate your risk of developing prostate cancer by age 80 as 15%. People with your background on average have a risk of developing prostate cancer by age 80 of 13%." As you mention, it would be good also to mandate that the chances of not getting the disease are also communicated: "This means that there is an 85% chance that you will not develop prostate cancer by age 80."

I don't have a full solution but I think there are major problems with the way people interpret information around risk and that standards need to be developed, and enforced, regarding how risk is communicated.

Overall, I am in agreement with your concerns.
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