AsianScientist (Jul 31, 2014) – Researchers have identified over 100 locations in the human genome associated with the risk of developing schizophrenia in what is the largest genomic study published on any psychiatric disorder to date. This research has been published in the journal Nature.
“The main aim of this 5-year project was to identify the markers that will enable the better and early identification of those who might develop schizophrenia and these include genetic markers,” said Professor Chong Siow Ann, Vice Chairman Medical Board (Research) of Singapore’s Institute of Mental Health (IMH), who is the Principal Investigator of this project.
Schizophrenia, a debilitating psychiatric disorder that affects approximately 1 out of every 100 people worldwide, is characterized by hallucinations, paranoia, and a breakdown of thought processes, and often emerges in the teens and early 20s. Its lifetime impact on individuals and society is high, both in terms of years of healthy life lost to disability and in terms of financial cost.
Despite the pressing need for treatment, medications currently on the market treat only one of the symptoms of the disorder (psychosis), and do not address the debilitating negative and cognitive symptoms of schizophrenia. In part, treatment options are limited because the biological mechanisms underlying schizophrenia have not been understood. The sole drug target for existing treatments was found serendipitously, and no medications with fundamentally new mechanisms of action have been developed since the 1950s.
In the genomics era, research has focused on the genetic underpinnings of schizophrenia because of the disorder’s high heritability. Previous studies have revealed the complexity of the disease (with evidence suggesting that it is caused by the combined effects of many genes), and roughly two dozen genomic regions have been found to be associated with the disorder. The new study confirms those earlier findings, and expands our understanding of the genetic basis of schizophrenia and its underlying biology.
In the present genome-wide association study (GWAS), the authors looked at over 80,000 genetic samples from schizophrenia patients and healthy volunteers and found 108 specific locations in the human genome associated with risk for schizophrenia. Eighty-three of those loci had not previously been linked to the disorder.
The study implicates genes expressed in brain tissue, particularly those related to neuronal and synaptic function. These include genes that are active in pathways controlling that are implicated in learning and memory, and pathways involved in signaling between cells in the brain.
Additionally, the researchers found a smaller number of genes associated with schizophrenia that are active in the immune system, a discovery that offers some support for a previously hypothesized link between schizophrenia and immunological processes. The study also found an association between the disorder and the region of the genome that holds DRD2—the gene that produces the dopamine receptor targeted by all approved medications for schizophrenia—suggesting that other loci uncovered in the study may point to additional therapeutic targets.
“The discovery of these 108 genomic regions has opened the door for further biological and clinical research to discover the genes that are directly linked with schizophrenia development and further understand the molecular mechanisms underneath the association of these genes with schizophrenia,” said Professor Liu Jianjun, from the Genome Institute of Singapore who is the Co-Principal Investigator of this project and the leader of the genetic study program of the project.
“These new findings will also open doors to allow researchers to examine and better clarify the underlying brain connectivity changes associated with these genes and genetic mechanisms. A better understanding of the genetic mechanism and underlying brain changes can potentially allow better detection of illness, monitoring of response with treatment and progression over time,” added co-author Adj Assoc Professor Sim Kang from the IMH.
This study is the result of several years of work by the Schizophrenia Working Group of the Psychiatric Genomics Consortium Psychiatric Genomics (PGC) which is an international, multi-institutional collaboration founded in 2007 to conduct broad-scale analyses of genetic data for psychiatric disease.
The 80,000 samples used in this study represent all of the genotyped datasets for schizophrenia that the consortium has amassed to date. The PGC is currently genotyping new samples to further study schizophrenia and additional psychiatric diseases, including autism and bipolar disorder.
Source: A*STAR; Photo: _DJ_/Flickr/CC.
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