Fresh insights into genetics of schizophrenia

Researchers are a step closer to unravelling the genetic underpinnings of schizophrenia following the largest genome-wide association study of the disorder ever undertaken.

An international consortium of 190 researchers from 135 institutions, including the Queensland Brain Institute (QBI), found significant associations with schizophrenia for five new and two previously-implicated locations on the human genome.

It has long been recognised that schizophrenia is highly heritable.

However, this new study has pinpointed novel regions of the human genome significantly associated with disease, and confirmed other recently reported genomic regions that may harbour disease-causing genetic variation.

According to Professor Bryan Mowry from QBI, the Queensland Centre for Mental Health Research and UQ’s Department of Psychiatry, who initiated and coordinated the Australian contribution to this study, these findings were made possible because of the unprecedented size of the study, with more than 50,000 participants.

“It provides a solid foundation for beginning to understand the mechanisms underlying the substantial genetic predisposition to schizophrenia,” Professor Mowry said.

The research was published in the latest issue of Nature Genetics.

Schizophrenia affects 1 in 100 people and its onset is typically in adolescence or early adulthood.

Psychosis (comprising hallucinations and delusions) is the hallmark of schizophrenia, but other symptoms such as personal neglect and amotivation are common, as is an increased risk of suicide.

Professor Mowry says that gaining a better understanding of the genetic architecture of schizophrenia will ultimately aid the earlier diagnosis and management of the disorder.

“If your genetic profile suggests you have a predisposition towards developing schizophrenia, it will be particularly important for you to avoid known environmental risk factors, such as smoking cannabis,” he says.

“We also expect that understanding the biological mechanisms underlying the disorder will lead to more robust therapeutics in future.”

The strongest genome-wide association finding in the study was to single nucleotide polymorphisms (SNPs) in a region containing numerous immune-related genes, suggesting schizophrenia may be triggered by autoimmune responses or infection.

Another SNP in a region linked to neuronal development was also implicated, suggesting a novel mechanism underlying schizophrenia.

The study also confirmed genetic overlap between bipolar disorder and schizophrenia, suggesting that these disorders have shared rather than separate roots.

(Source: The University of Queensland: Nature Genetics)