Podcast Review: The G Word – Diversity of genomic data and polygenic risk scores

In this 'The G Word' Podcast from Genomics England, London, guest host Dr Richard Scott (chief medical officer of Genomics England) talks to Dr Hilary Martin (group leader at the Wellcome Sanger Institute, Saffron Walden) about her work on rare recessive variants and polygenic risk, and in particular the Deciphering Developmental Disorders (DDD) study.

I'm in danger of sounding like a broken record again, but the Progress Educational Trust chose another podcast of great interest to me, having worked as a human geneticist in the 1990s and early 2000s, as well as also living with a rare genetic condition myself. I also have experience of working on the Avon Longitudinal Study of Parents and Children (ALSPAC) 1990s cohort, which was a precursor to the studies discussed here.

In his introduction, Dr Scott summed up the emotive nature of genomics by stating that it often triggers strong responses, including 'hope, fear and anger'. With Dr Martin's area of work – genomics, disease, populations, and ethnicity – certainly having its fair share of controversies in the past.

In the podcast, Dr Martin begins by successfully explaining her research in an easy-to-understand fashion. She is an engaging speaker and someone who is clearly very passionate about her work, having come from a family of geneticists. The conversation flows easily which is helped by Dr Scott who is well-informed, asking good questions covering a number of different facets of the topic. It was also fascinating for me to hear how far whole genome sequencing and genotyping arrays had developed since I left the field, particularly the greatly reduced costs and what can now be achieved.

The podcast can be broadly divided into three sections. In the first, Dr Martin discussed the field in general, explaining how human genetic variation can lead to rare and common diseases, and how these can be studied, while also highlighting the importance of population history and dynamics.

In the second, Dr Martin talked about her work on rare diseases, and the strategies used to study the underlying genetics behind these heterogenous conditions, and the challenges that researchers face in trying to identify them. Dr Scott described this as a 'needle from the haystack across a whole genome'.

While Dr Martin discussed her work on the DDD study and 100,000 Genomes Project, Dr Scott highlighted the potential benefit of this work in enabling families living with rare diseases to finally be given a definitive genetic diagnosis. Something I can personally relate to, with the genetic basis of my own condition for example, not being identified until some 16 years after my initial diagnosis. Although, I did feel that it would have been nice to also hear from some of the families living with rare conditions about their views on the topic.

Dr Martin then went on to talk more specifically about her work on diverse populations, particularly British South Asians, where she highlighted collaborative research with Genes and Health, and the Born in Bradford cohort. This was very interesting, particularly when she discussed the importance of understanding the structure and history of populations, and factors such as marriage patterns. Dr Martin acknowledging the culturally sensitive nature of the work and importance of community engagement and being especially happy that the 'participants were driving the conversation'.

In the third section, Dr Martin went on to talk about her research on common diseases and in particular polygenic risk scores for cardiometabolic disease, and their relevance to more diverse populations. Dr Scott noted that these had traditionally been based on data from populations of predominantly European ancestry.

Referring to the Genes and Health cohort again, Dr Martin's work showed that while some risk scores held true for more diverse populations, others were less relevant and that more research was needed to understand this. Dr Scott highlighted the importance of this research and agreed that much more work was needed in this area. With Dr Martin hoping that this would be of 'some clinical use one day, but of course it's a long road'.

Dr Scott concluded the conversation by thanking Dr Martin for her work, and particularly her thoughtful approach in making sure that 'our knowledge on genomics is relevant to all communities'. He then thanked the listeners and stated the aim of 'The G Word' podcasts were to 'highlight and debate the implications of genomics as it comes to the mainstream of healthcare and society'.

In summary, this is a great podcast that offers a clear introduction to the topic and is certainly worth listening to. However, I would like to have heard a few more voices, particularly from the families living with rare conditions and the different communities involved, to see how they viewed the issues first-hand. And also, more critical perspectives to give the piece more balance.

In an era of immense pressure on health services, I wonder how genomics will fit into the wider NHS strategy. Particularly when the COVID-19 pandemic exposed the health inequalities in society around ethnicity, poverty, and access to treatment. Better knowledge is great, but what if the same families are then not able to access the specialist services and support, they may need. I certainly do not think we should stop striving to push the boundaries of medicine in promising areas such as genomics but recognise the limitations of the system and funding available.