The Gene-iuses Behind Genetic Study in Leeds: The Nuances of Neonatal Screening

Anna Aksenova, Third Year Medicine

The Leeds Teaching Hospital Trust (LTHT) has taken part in a new and exciting research study called the Generation Study, offering newborns whole genome sequencing (WGS), to detect over 200 rare and treatable genetic conditions. The testing for the conditions is non-invasive, with blood samples collected from the umbilical cord after birth. The suspected conditions are then tested for within the following 28 days. Leeds General Infirmary and St James’ University Hospital are the participating hospitals from LTHT, amongst a number of other NHS trusts located nationally. The study is led by Genomics England in partnership with NHS England and is open to the general public. They aim to recruit over 100,000 participants, making it one of the largest studies to ever be conducted on neonates (Genomics England, 2025). Currently, the NHS routinely screens the newborns for 9 serious and potentially life-threatening diseases: sickle cell anaemia, cystic fibrosis, congenital hypothyroidism, phenylketonuria, medium-chain acyl-CoA dehydrogenase deficiency, maple syrup urine disease, isovaleric acidaemia, glutaric aciduria type 1 and homocystinuria. The Generation Study however, being an optional and supplementary test, offers to screen for a significantly higher number of rare treatable genetic conditions (200+), that often do not present until early childhood or adolescence. Another key aim is to improve symptom management and long-term health outcomes, for those with these disorders. NHS England (2025) hopes this will be accomplished by early detection of these disorders, as seen in the Generation Study.  

Whilst the benefits of newborn genetic testing include early diagnosis and treatment (or even prevention) of the disease, there have been some ethical concerns. Since children will be pre-symptomatically screened, they are potentially exposed to overtreatment, which may lead to iatrogenic complications. Due to poor prognosis, the study has excluded illnesses such as Alzheimer’s and Huntington’s disease from the list of disorders screened for, instead only screening for treatable conditions (Esquerda et al., 2020). Incidental findings also are a topic of discussion about the balance of benefits, costs and harms of testing on the patients and their families (Lantos, 2023). Parental views on the use of WGS have been studied, with concerns raised such as issues with informed consent, mistrust and use of the data collected. The Family System Theory also states that one event has potential to affect the whole family which would need to be accounted for (Holm et al., 2018). Whilst the general consensus was positive, there is a need for increased counselling, transparency and support of those participating (Joseph et al., 2016), which the Generation Study has committed to providing (Genomics England, 2025).

Globally, previous studies have alluded to many benefits to using WGS as a screening tool in neonates. WGS allows for specific genes to be identified and offer a molecular diagnosis for Mendelian disorders. Furthermore, within this study, WGS proved to have fewer false positives than basic screening tests offered. This means it identified more conditions and confirmed previously inconclusive results (Bodian et al., 2015). WGS is already used by the NHS in children when rare genetic conditions with varied differential diagnoses. However, using WGS as a screening tool does not rule out diagnosis for conditions that are non-genetic in origin or are multifactorial (Berg et al., 2017). There are further challenges of variants of unknown significance that would need to be investigated, to identify the potential risks of disease as often different variants will result in different characterisation of each disease (Chen et al., 2023).  Using WGS on such a large scale can also allow for variants to be identified within regional populations (Kuriyama et al., 2016). 

WGS has been used in neonates on one of the largest scales in the world, in the Generation Study. WGS provides screening for rare conditions to offer early treatment and prevention, and it may allow for more personalised medical care and better long-term health outcomes. Moreover, the data collected will aid healthcare research into these rare conditions, potentially allowing for new advances in treatments, specific genetic tests and become the future of neonatal screening. However, using WGS could impact the NHS economically and structurally, requiring the NHS to navigate psychosocial, ethical and legal conflicts that may arise by using such a large-scale screening type. However, the use of genomics could lead to better patient outcomes and reduce long-term health complications. The Generation Study could be transformative, prompting the use of WGS nationwide. 

Reference list:

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