Multiple Genetic Mutations Associated with Schizophrenia

Schizophrenia is typically caused by damage to several genes, rather than a single genetic mutation, according to research from Colombia University Medical Center that was published online May 21, 2014, in Neuron.

By comparing the sequencing data of 31 healthy controls and their parents to 231 schizophrenia patients and their unaffected parents, the researchers discovered several genetic factors that result in the disease. Specifically, they focused on loss-of-function (LOF) mutations, which influence the diagnosis and severity of schizophrenia.

Among cases of non-inherited schizophrenia, LOF mutations were rare yet had a significant effect on gene function, the investigators found. Additionally, they discovered many of the mutations that had been passed from parents to schizophrenia patients were LOF, while healthy controls were less likely to inherit LOF variants. The researchers asserted that genes with a low tolerance for variation were especially susceptible to the mutation.

“We identif(ied) 2 de novo LOF variants in the SETD1A gene, which encodes a subunit of histone methyltransferase — a finding unlikely to have occurred by chance, and provide(s) evidence for a more general role of chromatin regulators in schizophrenia risk,” the authors penned in the study.

“These mutations are important signposts toward identifying the genes involved in schizophrenia,” study contributor Maria Karayiorgou, MD, noted in a statement.

The findings echoed previous studies that associated malfunctions in chromatin regulatory genes with several psychiatric disorders.

“A clinical implication of this finding is the possibility of using the number and severity of mutations involved in chromatin regulation as a way to identify children at risk of developing schizophrenia and other neurodevelopmental disorders,” said Joseph Gogos, MD, PhD, who also contributed to the study. “Exploring ways to reverse alterations in chromatic modification and restore gene expression may be an effective path toward treatment.”