A human egg being fertilised using IVF

Polygenic scores and PGT: a problematic pairing

We explore a new type of test hitting the headlines and ask whether it could ever be approved for UK clinics

Recent publications have sparked debate around the controversial use of polygenic scores after some private US clinics have offered them to select embryos for use during IVF.

Certain types of preimplantation genetic testing are used in the UK but only when there is a high chance of the child being affected by a condition caused by a single gene. We explore why offering polygenic risk analyses may be a step too far.

Polygenic scores

Some genes are known to have a large effect on our risk of developing certain diseases, such as the BRCA genes’ role in breast cancer. For many other cancer types and other common conditions, such as cardiovascular disease or diabetes however, a person’s risk can be influenced by a wide range of factors. These include environmental and lifestyle circumstances, as well as many small pieces of genetic variation that each only have a tiny effect on risk.

Polygenic scores are a way of quantifying the cumulative effect of all of these small genetic influences on the chance of developing a particular condition. You can read more about the benefits and challenges of polygenic risk scores here, in our article.

Though polygenic scores are certainly useful for understanding and predicting common diseases at population level, there is a lack of evidence to support their usefulness for predicting disease risk in individuals. Studies such as the integrated cardiovascular risk tool being trialled in the North East of England are helping build an evidence base so that this can be properly evaluated in future.

Preimplantation genetic testing

Preimplantation genetic testing (PGT) covers several different types of tests that can be done on embryos that have been created through IVF. They all take place in the clinic, when the embryo is outside the mother’s body, so cannot be done on naturally conceived embryos.

In PGT, the DNA in the embryo’s cells is screened to detect particular traits or anomalies. There are several different types of PGT that can be used to look for different types of genomic variation:

  • PGT-A: Preimplantation genetic testing for aneuploidy (previously known as PGS). This type of test is mostly used to select embryos with a normal number of chromosomes, and can be recommended for patients who have experienced some types of infertility, for example, recurrent miscarriage.
  • PGT-M: Preimplantation genetic testing for monogenic conditions (previously known as PGD).
  • PGT-SR: Preimplantation genetic testing for structural rearrangements (previously known as chromosomal PGD) – used to detect genes or chromosome structural variants that are known to be carried by the parents who provided the egg and sperm. These are used when people have a known genetic disease in their family, or when a couple have already had an affected child.
  • PGT-P: Preimplantation genetic testing for polygenic risk – a new type of test that has been proposed and is being offered by some US clinics.

The legal situation in the UK

Any test where embryos are selected for use in fertility treatment based on whether they have (or do not have) specific characteristics can be controversial.

In the UK, embryo testing is regulated by the Human Fertilisation and Embryology Authority (HFEA) in accordance with the law as set out in the Human Fertilisation and Embryology Act 2008.

It is permitted only in limited circumstances, for example PGT-M can be used to detect conditions caused by a single gene (monogenic disorders). This is permissible only for conditions where “there is a significant risk that a person with the anomaly will have or develop a serious physical or mental disability, a serious illness or any other serious medical condition”.

The HFEA has made it clear, in a statement to The Times, that any fertility clinic in the UK that offered PGT-P would risk losing their licence to carry out fertility treatment and could also face criminal charges.

The statement reads: “The use of polygenic risk scores in preimplantation genetic testing is currently illegal in the UK. Embryo selection is only legal in the UK to avoid serious inherited illnesses, usually by means of preimplantation genetic diagnosis authorised by the HFEA, known as PGT-M or PGT-SR.”

“There is no scientific consensus that it is currently possible to test and identify genes for complex traits. Before this could be introduced into UK law it would need a shift in public policy, and a range of ethical concerns to be addressed, which would require parliamentary approval and the backing of society more generally.”

Please note: This article is for informational or educational purposes, and does not substitute professional medical advice.