The Generation Study: changing lives and building the evidence around genomic newborn screening

The Generation Study is a groundbreaking research study, run by Genomics England in partnership with the NHS in England, which is sequencing the genomes of 100,000 newborn babies to help understand whether we can improve the diagnosis and treatment of rare genetic conditions. Parents sign up during pregnancy and a sample – typically from the umbilical cord – is collected shortly after birth. If a rare condition is suspected, this is returned via NHS specialists for confirmatory testing and ongoing care.

The study launched last year, and in that time over 25,000 participants have joined and more than 60 'condition suspected' results have been returned by Genomics England to the NHS for confirmatory testing.

Making an impact

We're starting to hear from families who have joined the study, where results are making a positive impact. One recent demonstration of this is Freddie and his family – who joined the study before Freddie was born in April (see BioNews 1311).

Four weeks after being born and having his genome sequenced, Freddie was diagnosed with hereditary retinoblastoma, caused by a change in his RB1 gene. Retinoblastoma is a rare and aggressive form of eye cancer usually diagnosed in very young children. Around 44 children are diagnosed with retinoblastoma every year in the UK, and early detection is crucial for preserving vision. However, when there is no known family history, diagnosis often comes later, once symptoms have progressed.

In Freddie's case, there was no known family history and initially there were no signs that anything was wrong. He had passed all his eye tests in hospital, and it was only through genome sequencing in the Generation Study and subsequent confirmatory testing that his cancer was detected.

Very shortly after his diagnosis, Freddie was able to start treatment at Birmingham Children's Hospital, which is one of two specialist centres that treat retinoblastoma in the UK. This gives doctors the best chance to minimise the impact on his vision.

Freddie has undergone a mix of chemotherapy and laser treatment to treat the tumours in his eyes. Because of the nature of retinoblastoma and the genetic change involved, Freddie will need ongoing treatment, monitoring, and specialist care for the foreseeable future. He will be having regular eye screenings up until the age of 16 in Birmingham.

Freddie's ophthalmologist has said the chances of protecting his eyesight are greater because they were able to find out about his tumours earlier. His parents have also spoken positively about the impact the study has had for Freddie, remarking that it has 'changed his life phenomenally.'

Study aims

Freddie's story is just one example of why we believe genomics could change the lives of thousands of families and help get ahead of serious illness as a part of newborn screening, with the important caveat that the evidence needs to support its implementation alongside the existing NHS blood spot screen.

That's what we're looking to do through the Generation Study – evaluating the utility and feasibility of using genome sequencing to screen newborn babies for more than 200 treatable rare conditions. These conditions usually appear in the first few years of life, can be improved if caught early and can be treated in the NHS. This aims to improve their health outcomes and quality of life through more timely diagnoses, access to care and treatment.

As research, the study includes a specific consent process for parents outlining what to expect and any associated risks, for example a small chance of incorrect or uncertain results. This is the case with any screening programme and because we are still learning about how genetic changes cause disease or ill health. Recognising that receiving a result from the study can be a worrying time for families, we have worked with the NHS and charities to put supports in place – such as timely genetic counselling and access to patient organisations.

Screening isn't the study's only aim. We also want to:

• Enable discovery research – With parent's consent, babies' genomes and health data will be accessed for wider research about genes and health, so we can investigate new testing and treatment for genetic conditions in the future. Approved researchers will be able to access this data in a secure database called the National Genomic Research Library, without knowing babies' identities.
• Explore the risks and benefits of storing an individual's genome over their lifetime – We will continue to engage with the public, parents, healthcare professionals, researchers, rare conditions communities and policymakers to look at the possible benefits, risks, ethical and practical implications of storing an individual's genome over their lifetime.

Looking ahead

We are continuing to onboard new hospitals and supporting those already taking part, with 51 hospitals across England currently recruiting. By the end of the study, we're estimating we'll identify between 500 and 1000 babies with a suspected condition.

Every year thousands of babies are born in the UK with rare genetic conditions, but they can be hard to diagnose. On average it takes around five years for a rare condition to be diagnosed, at which point it has often progressed to the point where treatment, if it exists, is far less effective.

We believe genomics could have a transformative impact for newborn screening and offer faster diagnoses and access to treatment that could make a world of difference to children and their families. But we must be guided by evidence and are committed to continuing to deliver the study safely and transparently with the aim to help more families like Freddie's.

If you have any questions, please contact the Genomics England Generation Study team at generationstudy@genomicsengland.co.uk