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Genomics England's Generation Study Starts Enrolling First Newborns


MADRID – The Generation Study, a newborn genomics research project run by Genomics England in partnership with the UK's National Health Service, has enrolled its first families and plans to continue its phased rollout throughout the year.

At the Association for Molecular Pathology's AMP Europe 2024 meeting here on Monday, Amanda Pichini, clinical director at Genomics England and a genetic counselor, provided an update on the study, which plans to screen 100,000 newborns by genome sequencing.

The project has been planned over the past few years with input from families affected by rare conditions, NHS staff including midwives, and various other expert working groups, she explained. The goal is to improve the early diagnosis and treatment of genetic conditions. The study will run in parallel to routine newborn screening, which only tests for nine conditions in the UK at the moment.

Coming up with the list of conditions to screen for was difficult as "there is no right answer" and "a lot of different opinions," Pichini said. Last fall, the study decided to include 223 conditions, which requires analysis of more than 500 genes, and "erring on being a little bit more conservative," she said.

These have a well-established gene-disease association, can be detected by whole-genome sequencing, are highly penetrant "to the best of our knowledge," and have early or pre-symptomatic interventions available that improve patient outcome, she said. Interventions run the gamut from dietary changes to drug treatments to behavioral adjustments like avoiding sun exposure, and must be equally accessible to all patient in the NHS. Conditions that may change reproductive planning but do not have other interventions, such as many neurodevelopmental disorders, were not included for now but could be added later, Pichini noted.

For each disease, the researchers have come up with a list of variants to prioritize, as well as with a variant exclusion list, such as those that cause a very mild form of a disease. All variants are reviewed manually prior to their return, and no variants of unknown significance are reported.

The study has also developed a clinical pathway for each condition, starting with non-genomic confirmatory testing. A central case-management team will make sure a positive result is returned by a phone call from an NHS pediatric specialist who has expertise in the respective condition and can arrange follow-up care for the baby. The study has also collaborated with the NHS England National Genomics Education team to develop resources for training staff and will provide clinicians and parents with tools for "informed Googling" of conditions.

Even families with a negative test result will receive a report that states "no conditions suspected" and explains that this is "not a clean bill of health," Pichini said.

Women are approached about the study midway through their pregnancy and are consented just before giving birth. Pichini said that women who saw a poster about the study and expressed interest usually consented to participate, "but we don't know how many see the poster and don't express an interest," which the study aims to investigate.

Physicians and midwives have had "mixed responses" to the study so far, she noted, with some supporting it enthusiastically and others being worried that it may identify more cases than they can handle.

Overall, the Generation Study expects that about 1 percent of newborns will receive a positive result, or 1,000 of the 100,000 to be screened.

The first babies were enrolled in late March and early April at a handful of NHS trusts, she said, and the study plans to expand to additional trusts throughout England to ensure that the cohort will be diverse. Another goal is to decrease the testing turnaround time from a current 28 days to 14 days.

Government funding for the study is only confirmed until April 2025, but the hope is that more funding will become available "as the project gathers momentum," Pichini said.