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Genetic basis of schizophrenia: new insights
A new study sheds new light on the genetic underpinnings of schizophrenia. The study, from the international, multi-institution Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) is published today in the journal Nature. It involved a genome-wide association study (GWAS) on 36,989 schizophrenia cases and 113,075 controls. This represents the largest GWAS to date in any psychiatric illness. 128 independent associations were identified over 108 specific locations of the human genome associated with schizophrenia risk; 83 of these had not been previously reported in schizophrenia risk.

Schizophrenia is a heritable disorder present in about 1:100 of the population. It features hallucinations, delusions, and disordered thinking and exacts an enormous human and financial cost. Current therapies mainly tackle the psychosis element; there are no effective treatments for the cognitive elements of the disease. Recent research suggests that the genetic basis of schizophrenia is highly complex, involving interaction of many genes. The current study, using a total of 55 datasets from more than 40 different contributors, confirmed and built on this knowledge as a result of years of work from the Schizophrenia Working Group of the Psychiatric Genomics Consortium. One of the contributors, Dr Jo Knight of Canada's Centre for Addiction and Mental Health (CAMH) explains: "Large collaborative efforts such as this one are needed to identify genes that influence complex disorders…The result is a major advance in understanding the genetic basis of brain functioning in schizophrenia."

The study identified the importance of genes expressed in brain tissue, particularly those related to neuron functioning and of signalling via synapses. They included genes implicated in control of synaptic plasticity, which is crucial in learning and memory, and pathways in the cells receiving the signal. A smaller number of immune system genes were also identified, supporting hypotheses concerning links between schizophrenia and immunity. While many of these findings point to new insights into the aetiology of schizophrenia, associations at the dopamine receptor DRD2 and many genes associated with glutamatergic neurotransmission point to molecules already known to have potential therapeutic relevance to schizophrenia.

Senior author Dr Michael O’Donovan of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University School of Medicine concludes: "The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases…The wealth of new findings has the potential to kick-start the development of new treatments in schizophrenia, a process which has stalled for the last 60 years."


Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature (2014)doi:10.1038/nature13595

Press release: CAMH; available at [Accessed 22 July 2014]
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