New research led by the Wellcome Sanger Institute, using data held in the National Genomic Research Library, has uncovered fresh insight into how common DNA differences play a role in the development of rare brain conditions.

The study, published in Nature, looked at data from thousands of children with rare neurodevelopmental conditions as well as their parents, also drawing on the Deciphering Developmental Disorders (DDD) study. It showed that while their overall role is small, common genetic differences can help to explain why some people have a neurodevelopmental condition.

The study also found that common genetic differences, when present in the parents, may affect the chance of their child developing a neurodevelopmental condition, even if the child does not inherit those genetic differences directly.

In the longer term, these findings may help families and doctors to better understand, diagnose, and manage these conditions.

Rare neurodevelopmental conditions, those seen in less than one per cent of people, affect the growth and development of the brain in childhood and can lead to learning difficulties and other conditions such as small head size or seizures.

In about half of people with neurodevelopment conditions, the cause is a single, rare DNA change in either one or both copies of a gene that plays an essential role in brain development. But in some cases, there might not be a single genetic mutation behind the condition. Rather, it could be a mix between different types of genetic and environmental factors.

The researchers found that those with neurodevelopmental conditions, but no genetic diagnosis, have a higher number of common DNA differences associated with reduced cognitive ability and later-onset brain conditions than those with a genetic diagnosis. They estimate that common DNA differences accumulatively account for about 10 per cent of why some people develop a neurodevelopmental condition but others do not.

“It’s important that we understand the cause of neurodevelopmental conditions in all patients, not only those with a clear-cut single-gene diagnosis. While we found that common DNA differences only play a small role in the development of these conditions, this study gives a more informed view of how different types of DNA differences work together to cause them.

“In the future, research on this may ultimately help give families more information about their chance of having another affected child and could possibly help inform strategies to improve children’s outcomes. This research also highlights how large-scale genetic research can give new insights and we are extremely grateful to families for their participation and engagement as without them, this research would not be possible.”

Dr Hilary Martin

Senior author from the Wellcome Sanger Institute

“As they were preparing to publish these results, the study team were keen to incorporate feedback from parents whose children have neurodevelopmental conditions. Some of the issues explored in this paper are sensitive and have the potential to be challenging for families to hear; we were able to advise on how best to explain the findings to people who share our lived experience. I am grateful to the team for this opportunity, which I believe has been beneficial to the researchers and the patient community alike, and I hope that such collaborations become more commonplace in the future.”

Jillian Hastings Ward, MBE

Patient representative and former Chair of the Participant Panel at Genomics England

Rare disease