Brain Proteins LRRN3 and LRRTM3 Significantly Associated with Autism Spectrum Disorders

In collaboration with an international team, researchers from the Wellcome Trust Center for Human Genetics at University of Oxford have identified two brain proteins that are significantly associated with one’s susceptibility for autism spectrum disorders (ASD).

Anthony Monaco, from the Wellcome Trust Center, and his fellow researchers have found converging evidence that common genetic variants of the brain proteins LRRN3 and LRRTM3 “confer susceptibility to ASD.” The proteins for which the LRRN3 and LRRTM3 genes code have previously been implicated in brain development. Specifically, it is thought that LRRN3 plays a role in the development and maintenance of the nervous system, whereas LRRTM3 is part of a family of proteins that are thought to organize synaptic connections. The roles that these two genes are thought to have in brain development also makes them significant to ASD, as brain development is often impaired in individuals with ASD.

"A focused candidate gene study was carried out using association approaches to identify common variants in the UK cohort and in additional European populations,” Monaco explained. “This study covered four brain-enriched leucine-rich repeat candidates and taken together, there is converging evidence that common genetic variants in LRRTM3 and LRRN3 confer susceptibility to ASD. Future studies of these genes and their function will provide valuable insights into their role in ASD pathogenesis."

The researchers examined four candidate genes in 661 families from the UK, the Netherlands, Italy, and Germany, leading them to the conclusions about LRRN3 and LRRTM3, specifically. Monaco believes that this study, the results of which were recently published in Molecular Autism, is the first to provide such detailed information about genes and ASD risk.

"To our knowledge, this is one of the most comprehensive genetic analyses of association between these important genes in brain connections and ASD risk,” he said.