The Generation Study

The Generation Study is a research programme being delivered by Genomics England in partnership with the NHS. It aims to recruit 100,000 newborn babies, whose genomes will be sequenced after birth (with their parents’ consent). The study aims to facilitate the earlier identification of rare genetic conditions in babies, to gather genomic data for wider research purposes and to explore the risks and benefits of storing an individual’s genome over their lifetime.

The Generation Study has been developed following extensive consultation with the public, parents, families affected by rare conditions, healthcare professionals, scientists and policy-makers.

The study has three main aims.

1. Identify rare conditions in babies earlier. The Generation Study will evaluate the utility and feasibility of using whole genome sequencing to screen newborns for a larger number of childhood-onset rare genetic conditions, with the aim of improving their health outcomes and quality of life through more timely diagnosis and access to care and treatment.
2. Enable research. With parents’ consent, babies’ genomes and health data will be accessed for the purpose of wider research around genes and health, to facilitate investigation into new testing and treatments for genetic conditions. Approved researchers can access this data within a secure database called the National Genomic Research Library, though the participants’ identities are not disclosed.
3. Explore the risks and benefits of storing an individual’s genome over their lifetime. Genomics England and study researchers will continue to engage with the public, parents, healthcare professionals, rare disease communities and policy-makers, looking at the possible benefits and risks, as well as ethical and practical implications, of storing an individual’s genome over their lifetime.

The Generation Study is recruiting through participating NHS trusts in England.

• Parents sign up during pregnancy. Parents can contact the study team to sign up during their pregnancy, either in person during a hospital appointment or over the phone. The study team will help ensure that parents understand the study and its aims, answer questions and record parents’ consent.
• The sample is collected shortly after birth. An NHS practitioner will collect a blood sample from the newborn shortly after birth. This will be an umbilical cord sample or, in some cases, a heel prick. This sample will be used to analyse the baby’s DNA. Researchers will be looking for specific genetic variants that are known to cause one of the conditions being screened for.
• Families will receive results within a few months. In the early stages of the study, results will take a few months to be returned to families. As the study continues, however, it is expected that this timeline will reduce to two to three weeks. About 99% of babies will not have any of the gene changes being screened for.
• The sample and data are stored and used for research. Researchers will safely store the baby’s sample, digital files of their DNA and their parents’ antenatal data in the National Genomic Research Library. Researchers will also receive regular updates from the baby’s healthcare records, which will also be stored. This data is kept to facilitate learning about the identification and treatment of genetic conditions over time. Approved researchers will study the data to learn more about genes and health. The participants’ identities will not be visible to them.
• Participants will receive ongoing contact about the study. Participants will be contacted from time to time with updates about the study. Those running the study may also ask for feedback or whether the participants would like to take part in other research. When the child is around 16 years old, they will be asked if they would like to remain in the study. Participants can withdraw at any time.

• A bespoke set of four principles was developed for the Generation Study to guide condition selection.
• All of the conditions screened for have been approved by expert clinicians and NHS England. The condition list will be updated during the course of the study to reflect up-to-date evidence.

The Generation Study works as a screening test. It is different to a diagnostic genomic test, which takes a broader look at an individual’s genes to find a cause for a specific health problem. In the Generation Study test, the baby’s genome is only analysed for specific genetic changes in a defined set of genes believed to cause one of the conditions included in the study. These genetic changes are known as ‘pathogenic’ or ‘likely pathogenic’ variants. Variants of uncertain significance are not screened for. This approach aims to minimise the number of false positive results.

Because this is a screening test, a follow-up non-genomic test can be performed for the majority of the conditions to confirm whether the baby is affected with it or not. If a Generation Study participant presents with features of a genetic condition, they should be offered standard-of-care genomic testing according to the eligibility criteria outlined in the National Genomic Test Directory.

In the UK, all newborns are offered a newborn blood spot screening test around day five of life, during which biochemical markers in the blood are measured to check for nine different conditions. This is the standard of care for newborn screening in the UK. The Generation Study is exploring the implications of using a different approach to screening alongside the existing blood spot screening.

There are three possible outcomes of the Generation Study screening test.

1. A ‘no condition suspected’ result. Around 99% of participants will receive this result. It will be sent via email or letter directly from the Generation Study to participants, as well as to their GP. The result means that the participant is very unlikely to develop one of the conditions that has been screened for. However, because this is a screening test conducted for the purpose of research, babies could still develop one of the conditions tested for, as well as other health conditions. Standard-of-care referrals or genomic testing should still be arranged if indicated based on the baby’s health or family history.
2. A ‘condition suspected’ result. Around 1% of participants will receive this result. It means that the baby was found to have a gene change or changes believed to cause one of the conditions included in the study. Genomics England will return this result to the NHS via regional result coordinators within each NHS Genomic Medicine Service Alliance. The regional result coordinator will identify the appropriate NHS specialist team, who will contact the family to arrange further tests to confirm the diagnosis and begin ongoing NHS care.
3. There is a small chance that the test cannot be completed. This means that the baby won’t be a participant in the study, and the family will be informed by Genomics England by email or letter.

Currently, the study is scheduled to run until March 2025. It will be evaluated throughout, with the aim of understanding the process, impact and outcomes for participating families and the NHS. Results from the study will add to evidence that will inform future decisions about the use of genome sequencing for newborn screening, and will accelerate diagnosis and access to treatments for rare conditions.

• The Generation Study is a research programme being delivered by Genomics England in partnership with the NHS. It aims to recruit 100,000 newborn babies, whose genomes will be sequenced after birth.
• The study aims to facilitate the earlier identification of rare genetic conditions in babies, to gather genomic data for wider research purposes and to explore the risks and benefits of storing an individual’s genome over their lifetime.
• In total, 99% of participants will receive a ‘no condition suspected’ result, meaning that no further action is needed. For the 1% who receive a ‘condition suspected’ result, the appropriate specialist NHS team will contact the participant to arrange further tests, confirm the diagnosis and begin ongoing care.
• The Generation Study test should not be confused with the newborn blood spot screening test, which is offered to all newborns across the UK.

For clinicians

• Genomics England: Conditions list
• Genomics England: How we choose conditions
• Genomics England: The Generation Study
• NHS England: National Genomic Test Directory

For patients

• Genomics England: Conditions list
• Genomics England: How we choose conditions
• Genomics England: The Generation Study