A new study has linked 28 genes to rare developmental disorders and has estimated another 1,000 genes linked to these disorders are yet to be discovered. The authors are now calling for more open access healthcare data.
Research into the causes of developmental disorders has identified 285 genes linked to these conditions, including 28 newly associated genes. This study will enable diagnoses for around 500 families living with children who have rare conditions.
Published in the journal Nature, the authors collated anonymised healthcare and research data to create the largest available genetic resource for developmental disorders.
The study has been carried out by researchers at the Wellcome Sanger Institute, Radboud University Medical Center, OPKO Health’s GeneDx and their collaborators.
Dr Kaitlin Samocha, a first author of the study from the Wellcome Sanger Institute, said: “From previous studies we know that certain genes and types of mutation are more strongly linked to developmental disorders, which has allowed us to narrow our search. Combined with a much larger dataset, this has enabled us to identify 28 novel genes associated with developmental disorders.”
De novo mutations in genes
Globally, around 400,000 babies are born every year with new, spontaneous DNA changes – known as de novo mutations – that interfere with their development and can lead to disorders such as intellectual disability, epilepsy, autism, or heart defects. Every person is born with around 60 de novo mutations on average, though the vast majority do not lead to health problems.
Finding all of the undiscovered genes will require ten times the amount of data currently available, say the authors, which will only be possible with more open access to healthcare data. The authors highlight that around 60% of children born with a disorder do not have a diagnosis and the authors estimate that around 50% of these children will have a mutation in one of these unknown genes.
Because many conditions are extremely rare, the statistical analysis used to locate these genes requires large volumes of anonymised patient data that has not always been easily accessible. However, for this study, the researchers analysed 31,058 exome sequence ‘trios’, with each including sequences from a child with a developmental disorder, plus both of their parents.
The sample was created by combining existing research and clinical datasets from the Wellcome Sanger Institute, Radboud University Medical Center, and GeneDx. The scale of this dataset greatly increased the statistical power available to search for previously undiscovered mutations, and the authors then used an improved statistical test to determine whether individuals in the study had more mutations in the same gene than they would expect to occur by chance.
Discovering genes with data
Statistical modelling of the data estimated that approximately 1,000 more of these genes remain undiscovered.
Professor Matthew Hurles, lead author of the study from the Wellcome Sanger Institute, said: “This study has really shown the benefits of access to healthcare data, not least to the approximately 500 families living with a developmental disorder who had not been able to get a diagnosis until now. But our findings also estimate that we require ten times as much data to be able to identify all the genes linked to developmental disorders. As such, greater access to anonymised patient data is crucial to our understanding of these conditions and our ability to help the families living with them.”
Professor Sir Mark Caulfield, Chief Scientist at Genomics England, said: “This study demonstrates the value of combining genomic data with healthcare data in gaining novel gene insights that improve patient outcomes. It also shows that, rather than being something that just takes place in a lab, genomics is bringing about tangible advances in healthcare that directly impact patients and their families. It should serve as a call to action that more must be done to make anonymised patient data available for research.”
