Each year, around 6,000 babies in the UK are born with a rare genetic condition—conditions that, if detected early, could mean the difference between life-threatening complications and timely, life-saving treatment. But for many families, the journey to a diagnosis can take months or even years, often leading to missed opportunities for early intervention. Genomics England is on a mission to change that with The Generation Study, a groundbreaking initiative to sequence the genomes of 100,000 newborns.

Genomics England is a world leader in genomic research and innovation. Established by the UK government and a partner of the National Health Service (NHS), Genomics England plays a pivotal role in advancing genomic medicine with a focus on providing whole genome sequencing diagnostics and empowering researchers to discover new treatments—all while keeping patients and participants at the heart of it.

The Generation Study is a research project by Genomics England in partnership with the NHS that was announced as part of the Newborn Genomes Programme in 2022. The study aims to sequence the genomes of 100,000 newborns to identify and potentially treat rare genetic conditions earlier to improve health outcomes. The study officially launched in October 2024.

• Recruitment: The study aims to recruit 100,000 newborn babies, with their parents' consent.
• Sample collection: A blood sample will be collected shortly after birth. 
• Sequencing and analysis: The genomes of the newborns will be sequenced and screened for more than 200 rare but treatable conditions.
• Results and follow-up: Families will be contacted with the results of the study and will be kept updated about the study for the next 16 years.
• Data storage and research: The baby's samples and health data, a digital file of their DNA, and antenatal data will be stored and used for research purposes.

During the development of The Generation Study, investigators had to decide which conditions to include in the screen. With thousands of genetic diseases to choose from, narrowing the list to screen for a specific set of conditions, genes, and variants required a rigorous, evidence-based approach.

Genomics England selected conditions according to four core principles:

1. There is strong evidence that the genetic variant(s), causes the condition and can be reliably detected.
2. A high proportion of individuals who have the genetic variant(s) would be expected to have symptoms that would have a debilitation impact on quality of life if left undiagnosed.
3. Early or pre-symptomatic intervention for the condition has been shown to lead to substantially improved outcomes in children.
4. Conditions screened for are only those for which the interventions are equitably accessible for all.
   
   

One of the most critical challenges in The Generation Study was the monumental task of ensuring that every gene included in the screening is backed by trusted, evidence-based variant content. With 100,000 newborns undergoing whole genome sequencing, the stakes are incredibly high—there is no room for error in identifying disease-causing variants or in excluding benign ones.

The challenge lies in the sheer volume of data required. Each gene tested must be supported by an extensive body of scientific evidence and validated variant content, ensuring that the genomic insights provided are accurate, clinically actionable, and reproducible. Collecting, curating, and verifying this evidence demands collaboration across scientific literature, clinical databases, and expert consensus, all while adhering to rigorous standards of precision and reliability.