Event Review: Polygenic Risk Prediction in Diverse Populations and Contexts – Scientific and ethical considerations

Every month, the Ethical, Legal and Social Issues (ELSI) Hub hosts 'Friday Forum', an opportunity for presenters around the world to discuss a range of different issues relating to ELSI in genetics and genomics. In January, the ELSI Friday Forum focused on an approach to genetic data known as polygenic risk scores (PRSs). The session featured speakers Dr Alicia Martin, an assistant professor at Harvard Medical School in Boston, Massachusetts, and Professor Malia Fullerton from the department of Bioethics and Humanities at the University of Washington School of Medicine in Seattle.

Dr Martin started the session with an introduction to the concept of PRSs as an assessment of an individual's risk with regards to certain conditions or traits. PRSs are not used as a diagnostic tool, but instead have potential in a risk management context, where an individual's PRS could influence the type of advice they receive from healthcare professionals. For example, if an individual was identified as having a higher risk of breast cancer from their PRS, their healthcare professional might suggest more frequent breast cancer screening tests as a precaution. As a tool used in this way, PRS can be added to long-established individual risk factors as age or lifestyle choices.

There is, however, a catch with the accuracy of PRSs. Although it may not be surprising to those familiar with scientific studies, Dr Martin was quick to note that there is a significant data bias within genomic studies, in which people of European descent are highly overrepresented. Consequently, one subset of genetic variation is well understood while other subsets are not. What this means for PRSs is that they are more likely to be meaningful for people of European descent than they are for people of non-European descent.

Thus, there are a number of serious ethical considerations that need to be made when considering future uses of PRSs. It is on this theme that the second speaker, Professor Fullerton, shared her professional experience. She is one of several scientists working on the Electronic Medical Records and Genomics (eMERGE) Network project, with the aim of producing a genome-informed risk assessment (GIRA) for 25,000 participants. Professor Fullerton highlighted a number of ethical considerations that her team needed to address, including the ways in which biased data must be accounted for. For example, of the ten medical conditions eMERGE is testing for with its GIRAs, only five had validated genetic studies for all participants regardless of descent group. The eMERGE team notified participants of this fact throughout the process.

After both panellists spoke, the session moderator, Alham Saadat, asked both Dr Martin and Professor Fullerton questions about their research. Saadat's questions were accessible, regardless of your level of prior knowledge about the subject, and helped to elucidate some of the uses of PRSs, as well as some of the different ways you could think about PRSs and genomic research more broadly from an ELSI perspective. I found these questions to be particularly helpful in consolidating my understanding of the subject after listening to the other two, more academic, presentations.

This does lead into my main problem with the discussion, which was the slight difficulty I faced engaging with the content without any prior knowledge about PRSs. Upon reflection, I thought maybe the presenters' slides could have contained more bullet point summary notes at the start, which would have made it much easier to follow along throughout the rest of the talk. Saadat's questions, however, were very useful for bringing all the information together and making PRS as a holistic idea clear in my mind.

A facet of the forum that I found to be particularly interesting was Dr Martin's initial, anthropological explanation about genetic variation as based on the migration patterns of early humans. I really appreciated this as a starting point, partially because my own academic background is in anthropology, but also because it grounded the real, physical world, rather than in the realm of theory and science, which these presentations can sometimes get caught up in. For the same reason, I enjoyed the contrast of information between Dr Martin's introductory presentation followed by Professor Fullerton's recount of a scientific study that was actually implementing the concepts that had just been introduced.

Overall, I enjoyed my first experience with ELSI's Friday Forum. I would have appreciated a slightly more basic introduction at the start of the discussion, just to really ensure that I was able to follow along with the content that came after. I would recommend this presentation to anyone interested in genetics and genomics, and especially those that already have some prior knowledge.