Researchers from the Geisinger Health System in Pennsylvania, USA, compiled 241 genes related to brain dysfunction and discovered 17 new gene mutations associated with brain developmental disorders, including autism, epilepsy, schizophrenia, and bipolar disorder. The related research results were published on January 28, 2016 in the journal JAMA Psychiatry.

The researchers investigated nearly 400 studies from March 28, 2003 to May 7, 2015 from the PubMed database, which included a large number of patients with brain development disorders. The data that researchers are concerned about includes the following aspects: pathogenic loss of function sequence and structural variation data in the whole genome, phenotype data of six different brain diseases (including intellectual disability, autism, ADHD, schizophrenia, bipolar disorder, epilepsy), candidate genes of interest in large-scale studies or case reports. Researchers conduct hierarchical and multi-level data integration studies on these data.

The researchers classified the discovered genes into four levels: level one contains genes with three or more de novo pathogenic loss of function variants, level two contains genes with two de novo pathogenic loss of function mutants, level three contains genes with one de novo pathogenic loss of function mutant, and level four contains genes with only hereditary pathogenic loss of function mutants.

Using this method, researchers identified 241 genes associated with brain dysfunction and identified 17 new genes related to autism or other brain disorders. Overall, researchers classified 59 genes as level one, 44 as level two, 68 as level three, and 70 as level four. Among these 241 genes, 7 have been proven to be directly related to brain disorders, and 10 are candidate genes. The researchers stated that "the identification of new pathogenic genes for brain diseases has increased human understanding of the biological mechanisms of brain diseases and laid the foundation for targeted therapies. Now we know that at least 40% -50% of brain disorders are caused by individual gene mutations, and such research has made human understanding of brain diseases clearer." The research team also created an online database for other researchers or clinical doctors to use, which contains specific information and classifications of 241 genes.

Reference: A Cross-Disorder Method to Identify Novel Candidate Genes for Developmental Brain Disorders