Queensland scientists are closer to effective treatments for schizophrenia after uncovering dozens of sites across the human genome that are strongly associated with a genetic predisposition to schizophrenia.
The study, published in internationally prestigious Nature magazine, involved University of Queensland’s Professor Bryan Mowry, who said it was the world’s largest molecular genetic study into a psychiatric disorder.
Professor Mowry, from UQ’s Queensland Brain Institute and the Queensland Centre for Mental Health Research, said the study found 108 sites, 83 of which were previously unidentified, that formed the genetic underpinnings of schizophrenia.
“This provides the potential for understanding the causes of the illness and for discovering new treatments,” he said.
He said these locations were not randomly distributed across the genome but converged upon genes that were expressed in certain tissues, particularly the brain and in tissues with important immune functions.
“These are very exciting findings that will no doubt bring hope to the quarter of a million Australians who have schizophrenia and to their families and carers,” Professor Mowry said.
“This study constitutes a rapid advance in our understanding of the genetic architecture of schizophrenia, opening the door to expanding our understanding of its underlying biology.”
Schizophrenia is a highly-inheritable, debilitating psychiatric disorder that affects about one in every 100 people worldwide, and is characterised by hallucinations, disturbed beliefs and a breakdown of thought processes.
It is ranked ninth in the global burden of illness and is estimated to cost Australian society $5 billion a year.
Professor Mowry said that despite the huge cost to individuals and to society, it was only in the past five years that substantial progress had been made.
“Many of these findings implicate genes that are involved in transmitting signals from one neuron to another, opening up potential therapeutic avenues,” he said.
“Interestingly, by far the strongest genetic finding links schizophrenia to a region previously identified in autoimmune diseases, implying the possibility of an autoimmune pathology in the disease, and is one that warrants further investigation.”
Using DNA samples from 36,989 schizophrenia patients, researchers used a genome-wide association study to find genetic variations between the patients and 113,075 control samples.
Schizophrenia’s genetics revealed
“A huge international effort was made to increase sample size, because, although previous studies had indicated a small number of genetic signals, sample sizes weren’t large enough to confirm definite genetic associations,” Professor Mowry said.
“By screening the DNA of people with schizophrenia and those without it at millions of DNA markers across the human genome, we were able to determine which markers were statistically significantly associated with this disorder.
“The next steps will involve determining the functional basis of these genetic signals and how they interact together to cause illness, and then develop new therapeutic interventions.”
UQ partnered with more than 200 organisations in the Schizophrenia Working Group of the Psychiatric Genomics Consortium, including researchers from QBI, QCMHR and the Royal Brisbane and Women’s Hospital Department of Psychiatry.
Source Darius Koreis – University of Queensland
Contact: University of Queensland press release
Image Source: The image is credited to PublicDomainPictures and is in the public domain
Video Source: The video “Schizophrenia’s genetics revealed” is available at the University of Queensland YouTube page
Original Research Full open access research for “Biological insights from 108 schizophrenia-associated genetic loci” by Schizophrenia Working Group of the Psychiatric Genomics Consortium in Nature. Published online July 22 2014 doi:10.1038/nature13595
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
“Biological insights from 108 schizophrenia-associated genetic loci” by Schizophrenia Working Group of the Psychiatric Genomics Consortium in Nature. doi:10.1038/nature13595
