Researchers from the Wellcome Sanger Institute (Cambridge, UK) and colleagues have performed a genome-wide association study to determine if common genetic variation has an impact on the risk of many rare genetic disorders.
The paper, which has been published in Nature, may help researchers better understand the neurodevelopmental disorders that thousands of children are born with every year.
The paper utilizes data collected during the Deciphering Developmental Disorders study in which DNA was collected from thousands of patients whose neurodevelopmental genetic disorders were considered to be monogenic. The genomes of 6987 children suffering from a range of disorders such as autism were compared with the genomes of healthy individuals.
“This is the first ever large-scale study of the role of common genetic variants in rare neurodevelopmental disorders, and was only possible due to the large cohort of patients in the Deciphering Developmental Disorders study,” commented Hilary Martin (Wellcome Sanger Institute), one of the authors of the paper.
“Until now, rare developmental disorders have been thought to be caused by a single gene having a huge effect, but our study shows that this might not be the whole story,” stated lead author, Mari Niemi (Wellcome Sanger Institute).
It was determined that common genetic variance affects the risk of having a neurodevelopmental disorder. Further analysis of genomes from a separate population of child–parent trios confirmed their conclusions that monogenic disorders are influenced by common variants.
“We discovered that common variants that work together to influence common diseases such as schizophrenia also seem to contribute to rare developmental disorders,” explained Niemi.
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The study also aimed to establish whether the common variant risk affected the clinical presentation of the disorder. “Our study shows for the first time that common genetic variants could affect the risk of rare developmental disorders, and some of their characteristics,” said Jefferey Barnet (Wellcome Sanger Institute), a senior author of the paper.
“As we learn more about the genetic causes of both rare and common diseases, it is increasingly clear that many different types of genetic variation play important roles in all cases,” continued Barnet.
These findings may change the way neurodevelopmental disorders are categorized. “This [study] shows that the genetics of rare diseases are more complicated than originally thought, and we hope it will change how researchers and clinicians think of rare versus common diseases,” concluded Martin.
Sources: Niemi MEK, Martin HC, Rice DL et al. Common genetic variants contribute to risk of rare severe neurodevelopmental disorders. doi:10.1038/s41586-018-0566-4 (2018) (Epub ahead of print); The Wellcome Sanger Institute. Rare genetic disorders more complex than thought. Press release: www.sanger.ac.uk/news/view/rare-genetic-disorders-more-complex-thought