Polygenic Risk, Polygenic Scores, Polygenic Indices: What Are They? What Should Be Done with Them?

The fourth session of the 2025 PET (Progress Educational Trust) Annual Conference was entitled 'Polygenic Risk, Polygenic Scores, Polygenic Indices: What Are They? What Should Be Done with Them?', and could not have been more timely. Chaired by the science writer, broadcaster and author Dr Philip Ball, the session focused largely on the practicalities and ethics of PGT-P. This is a form of preimplantation genetic testing, involving polygenic scores, whose use is currently (supposed to be) prohibited within the UK.

The session was foreshadowed by the publication of reports in the Guardian and Times newspapers. A few days prior to the conference, the Guardian reported that patients in the UK were attempting to circumvent the prohibition of PGT-P by sending genomic data related to their embryos to a US company for testing (see BioNews 1319). Then the day before the conference, The Times reported on US companies offering 'IVF for genetic optimisation', meaning PGT-P.

Most attendees at the conference had seen these news stories, and the three speakers at this session tackled the issues raised head-on. Those speakers were Dr Emma Meaburn (behavioural geneticist at the Centre for Brain and Cognitive Development at Birkbeck University of London), Dr Dorit Barlevy (senior researcher at the Centre for Medical Ethics and Health Policy at Baylor College of Medicine in Texas), and Professor Angus Clarke (emeritus professor of clinical genetics at Cardiff University). They pulled few punches as they discussed the merit of using PGT-P to select embryos.

Dr Meaburn's presentation was entitled 'The ABCs of PGSs: Unpacking Polygenic Scores. She began by clarifying the terminology, explaining that polygenic scores are sometimes referred to as polygenic risk scores (particularly in the context of predicting disease) or as polygenic indices (particularly in sociological contexts, where care is being taken not to imply a value judgement where none is intended).

Starting with 'A' for applications, she was keen to distinguish between using polygenic scores within population health to try to predict which individuals (usually adults) are at elevated risk of developing certain conditions (see BioNews 1192, 1285 and 1316), and using PGT-P to rank and prioritise embryos based on what polygenic scores say about the likelihood of a resulting child developing a certain trait (see BioNews 1130, 1137 and 1232). She then went into some detail explaining how polygenic scores are developed, building upon a comment piece she had written for BioNews (see BioNews 1302).

She observed that there are more than ten different ways of calculating a polygenic score, and that these typically involve adding up many small genetic influences. She said that it is easy to oversimplify, or otherwise misconstrue, the meaning of polygenic scores – particularly in the context of embryo selection. One complicating factor is that selecting for (or against) one trait may involve inadvertently selecting for (or against) another, in ways that aren't yet fully understood.

Dr Meaburn concluded by cautioning that public-facing communication about what polygenic scores are – and what they aren't – is challenging. (She then added, self-deprecatingly, 'I may be learning this now'.)

This challenge was explored by Dr Barlevy, whose presentation was entiled 'The Ethics of Polygenic Embryo Screening: At the Crossroads of Choice and Acceptance Amid a Landscape of Uncertainty'. She discussed research into how patients and clinicians understand PGT-P, highlighting the fact that patients she had interviewed tended to be respectful of other patients' interest in using PGT-P, even if they were not interested in using it themselves. It was also apparent that patients and clinicians alike were keener for PGT-P to be used in relation to medical conditions than for non-medical traits.

At the same time, many of the clinicians she had interviewed were concerned about a lack of accuracy (or at least a lack of certainty) when it comes to PGT-P, and said that this would make it more difficult for them to counsel patients. Clinicians were also concerned – keeping in mind that fertility patients can already be anxious at the best of times – that anxiety could be exacerbated by the offer of PGT-P, perhaps making patients vulnerable to people who are pushing such testing.

Dr Barlevy's takeaway was that many of ethical concerns voiced about PGT-P are similar to those highlighted when PGT-M and PGT-A first became available (see BioNews 1320a). There were initial reservations about these earlier forms of PGT, but clinics in the USA had broadened the availability of these tests to a greater number of patients, as time passed.

Professor Clarke was next, with a presentation entitled 'The Seduction of Polygenic Testing in PGT: Irresistible but Pointless?'. In this presentation, he developed views that he had expressed previously when quoted by the Guardian ahead of the conference, and then in his own comment piece for BioNews (see BioNews 1318).

He began by echoing Dr Meaburn's point that PGT-P needs to be distinguished from the use of polygenic scores in population health, although it should be remembered that the latter is a subject of debate in its own right (see BioNews 1212). He then warned against 'reflexive prediction', whereby the results of PGT-P could become a self-fulfilling prophecy. Would parents invest more in a child selected for certain abilities? What would be the burden on that child, of failing to live up to the expectation set by the relevant polygenic scores?

Professor Clarke was also robust in criticising those who offer PGT-P to fertility patients, or who might be tempted to do so. He criticised the idea that just because so much of fertility treatment is now a commercial transaction, this therefore makes it acceptable to use a marketing approach for the promotion of PGT. 'For some it will be irresistible, and they will be exploited,' he said.

The three presentations were followed by an equally robust discussion. The first contributor from the audience – Professor David Curtis, of University College London – argued that polygenic scores are not going to improve, and that their current utility (such as it is) 'is all you are going to get'. Dr Meaburn responded with a slightly more optimistic view of the matter, arguing that there is likely to be some improvement in our understanding (particularly regarding the influence of rare variants), and that methodology is developing to explore marginal gains in the accuracy of scoring.

Some of the discussion – both on the speaker panel and among the audience – concerned the Guardian article, and its description of 'an apparent legal loophole' in the UK's prohibition of PGT-P. Julia Chain – chair of the UK fertility regulator, the Human Fertilisation and Embryology Authority (HFEA) – offered clarification from the audience. 'There is no legal loophole', she said. 'PGT-P is illegal in this country. End of story.'

Dr Cristina Hickman, an embryologist – also the founder of Avenues, the fertility clinic in London that had treated the patients discussed in the Guardian article – explained in a contribution from the floor that the patients requested their embryos' genomic data and then 'went straight to the Americans' for PGT-P, without her clinic's knowledge. She argued that 'PGT-P should be legalised so we can be involved in a process so it can be done properly', and likened her argument to the case for legalising recreational drugs (which does not necessarily involve endorsing the use of such drugs).

This was followed by a contribution from Dr Shereen Tadros, from Great Ormond Street Hospital, who questioned whether Avenues was obliged to comply with patient requests for the genomic data of embryos. Speaking of her own work in clinical genetics, Dr Tadros observed: 'There is data we do hold that we don't release to every patient – for example, next-generation sequencing data. We don't release incidental findings unless there is something actionable to do.' She asked the audience if 'just releasing everything' was the correct thing to do, and argued that sometimes it was incumbent upon clinicians not to simply do whatever the patient wishes.

Later in the conference, during a concluding keynote presentation, Julia Chain reiterated her statement that PGT-P is illegal in the UK (see BioNews 1320b). She said: 'Licensed clinics in the UK are responsible for testing based on what is permitted in the HFE Act and, therefore, should not offer such testing'.

The exchange between Chain, Dr Hickman and Dr Tadros captured a certain tension that ran through session four, concerning whether and how fertility clinics – and fertility patients (particularly those with sufficient wealth to drop $50,000 on an add-on) – are actually governable in a globalised fertility market.

It was clear from the session that while PGT-P poses challenges, these challenges aren't just about polygenic scores being difficult to understand (although there is that) – they're also about regulatory scenarios that are tricky to navigate. This leads to the fundamental question that PET was originally set up to ask, when it was founded more than three decades ago – what kind of reproductive choices should society enable, and what protections are owed to those who make these choices?

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PET would like to thank the sponsors of this session (the British Fertility Society) and the other sponsors of its conference (ESHRE, PRECAS, Remaking Fertility, the Adelphi Genetics Forum, the Anne McLaren Memorial Trust Fund, Born Donor Bank, CooperSurgical, Ferring Pharmaceuticals, Merck, Salve, Theramex, Xytex, Juno Genetics and the Institute of Medical Ethics).

Register now for PET's next free-to-attend online events.

• Fertility and the Workplace: Can Employers Help? Should They?, taking place online on Wednesday 14 January 2026 – register here.
• Understanding Egg Donation: The Give and Take, taking place online on Wednesday 28 January 2026 – register here.
• Ancestry, Ethnicity, IVF Outcomes: Why Do Some Patients Fare Better than Others?, taking place online on Wednesday 4 February 2026 – register here.