Genomics 101: What is the Generation Study?

In this series, ‘Genomics 101’, we go back to basics and explore some of the most important topics in genomics. In this blog, we talk through the Generation Study, how it was designed, and what it aims to do.

First things first, what is the Generation Study?

The Generation Study is a research study that will sequence the genomes of 100,000 newborn babies.

It will use a technique known as whole genome sequencing to analyse the genetic codes of newborns, to look for a defined set of treatable rare genetic conditions.

The study is being carried out by Genomics England in partnership with the NHS.

When will it begin?

Recruitment to the study will begin in 2024.

Initially, all participating newborns will be from a small number of NHS hospital Trusts however, additional Trusts will also begin recruiting at later dates.

We expect as many as 40 NHS Trusts across England to participate over the course of the study, which runs until March 2025.

Development, research, and public engagement for the study have been ongoing since 2021.

What does the Generation study aim to do?

The study has three key aims.

Firstly, it aims to identify treatable rare conditions in babies earlier. This will allow for more timely intervention and treatment, supporting a better quality of life for babies and their families.

Secondly, the study is designed to support discovery research that will help us better understand rare genetic conditions. This could lead to new diagnostic tools and treatments, and improvements in existing therapies.

And finally, the study will look at the benefits and risks of storing a baby’s genome throughout their lifetime. Storing someone’s genome could allow it to be reanalysed later in their life if needed, enabling access to new developments in genomics.

Do parents and newborns have to take part?

No! Parents and newborns do not have to take part just because they are at one of the participating Trusts. Like all research, the Generation Study is optional and by consent only.

Parents will be approached around midway through pregnancy (at about 20 weeks) to invite them to take part in the study.

We must have clear parental consent to take a sample, sequence, and store the baby’s genome.

How is this different to NHS newborn screening?

The NHS already offers newborn blood spot screening (the ‘heel prick’ test) to all babies when they’re about 5 days old. This already well-researched NHS service tests for 9 rare, treatable conditions.

Parents will still be offered the heel prick test for their baby, which the NHS recommends.

Where will the babies’ genome be stored?

For those that do consent, any data collected is securely kept in the National Genomic Research Library, where it can be accessed by approved researchers. This data is de-identified, meaning babies’ identities will not be visible to researchers.

What if parents change their minds?

It is completely okay if parents change their mind after sequencing.

Parents can withdraw from their child from the study at any point before their child turns 16, and their data will be removed from the National Genomic Research Library.

When the child is around 16 years old, they will be asked to give their own consent for the study.

What conditions will be screened for?

We have taken great care in choosing more than 200 conditions that the study will screen for.

The full list can be found here. It contains the scientific name of each condition, along with the gene that is associated with it.

There are more genes than conditions because one condition can be caused by several different genes.

How were these conditions chosen?

Deciding which conditions to include was an important part of the Generation Study.

Guided by conversations with the public, people living with rare genetic conditions, and healthcare professionals, we came up with criteria for conditions that would be included:

A) We can reliably detect the gene changes that cause the condition

B) If undiagnosed, the symptoms of the condition would have a severe impact on the child

C) Early intervention would substantially improve the child’s quality of life compared to intervention after symptoms have started to show

D) Treatment for the condition is equitably accessible for all in the NHS in England

More information about these principles can be found on the Choosing conditions webpage.

So, is the list final?

In short, no. The list of conditions may change throughout the study in response to any new evidence that is found. Any changes made will be highlighted in an amended published list.

It is important that all the conditions on the list can be successfully identified using sequencing technology, and that treatment options continue to be available.

We will work with the NHS to ensure that this remains true throughout the study, for every condition on the list.

Can you share a specific example of a condition you are looking for?

Around 14 babies each year are born with a condition on the list called Severe combined immunodeficiency (SCID).

Newborns with this condition have an immune system that does not properly function, so infections can be dangerous and even life-threatening. Without treatment, babies born with SCID usually die before they are one year old.

If diagnosed early, babies can receive a bone marrow transplant which replaces their faulty immune system and protects them from dangerous infections, effectively curing their condition.

How many babies in the study are expected to have one of these rare conditions?

Out of the 100,000 sequenced, we anticipate that around 1% (1000) newborns will be suspected of having one of the genetic conditions tested for in the study.

Parents of newborns will be contacted by a specialist clinician if their child has a suspected condition. Otherwise, parents will be informed by Genomics England that no gene changes causing the conditions in the study were found.

Importantly, the study does not cover all health conditions – so it is important that parents still speak to their GP if they are worried about their baby’s health.

So, how have you involved parents and the public in designing the study?

The study was carefully designed with the help of members of the public.

In 2021, we carried out a dialogue with 130 members of the public to gather their views on whole genome sequencing for newborns. The group was cautious but supportive, and the advice they gave us was used to carefully design the study.

More information about this dialogue can be found in the report.