These studies show that there are common variants increasing risk for schizophrenia, albeit representing small individual effects, and suggest that even larger samples may succeed in uncovering additional variants of pathophysiological importance, further illuminating the mechanisms of this devastating illness.
Evanston, IL (Vocus) July 2, 2009
The July 1, 2009 advance online edition of the journal Nature includes three companion papers describing the results of genome-wide association studies (GWAS) of schizophrenia. Schizophrenia is an elusive and severe psychiatric disorder that affects up to 70 million people worldwide. The causes of schizophrenia remain largely unknown and there is no cure, though for some individuals the current treatments work well. There are multiple factors that increase the risk for schizophrenia, of which genetic factors are the most prominent, though not precisely identified yet. This highlights the need for a better understanding of the pathways leading to schizophrenia to enable development of better treatments.
Dr. Pablo Gejman, Director of the NorthShore University HealthSystem (NorthShore) Center for Psychiatric Genetics, led one of these three international collaborations, the Molecular Genetics of Schizophrenia (MGS). The MGS publication is entitled “Common variants on chromosome 6p22.1 are associated with schizophrenia.
Each study analyzed several thousand individuals with hundreds of thousands genetic markers distributed along the human genome, conducted the statistical analysis of their sample, and then shared data of their top results for a meta-analysis. The three samples combined comprised over 8,000 schizophrenia cases and over 19,000 control samples of European ancestry. “The combined analysis of the three datasets highlighted a region in chromosome 6p22.1 that is associated with schizophrenia," said Dr. Gejman.
The 6p22.1 region includes a histone gene cluster (protein “spools” around which DNA wraps and affect the degree to which genes are turned on and off) and multiple immunity-related genes, suggesting a variety of possible pathophysiological mechanisms in schizophrenia, from abnormal transcriptional regulation to autoimmunity and maternal infections.
Dr. Gejman said, “These studies show that there are common variants increasing risk for schizophrenia, albeit representing small individual effects, and suggest that even larger samples may succeed in uncovering additional variants of pathophysiological importance, further illuminating the mechanisms of this devastating illness.”
Dr. Alan R. Sanders, a collaborator at NorthShore, states, “Schizophrenia is largely a genetic disease, though a complex one, and people who have close family members with schizophrenia are somewhat more likely to get this chronic, debilitating brain disorder. It usually begins in adolescence or early adulthood, and is characterized by hallucinations, delusions, disorganized thinking and behavior, and loss of interest and initiative. Chronic impairment in social functioning remains the more prevalent disease course, even with treatment.” Dr. Sanders further noted that, “Unlike the European ancestry only samples of the companion papers, the MGS sample also includes an African American (AA) subsample comprised by over 2,200 individuals. The AA GWAS results supported previously reported schizophrenia associations for the genes, ERBB4 on chromosome 2q34 and its ligand, neuregulin (NRG1 on chromosome 8p12).
The NorthShore team expects to continue to generate knowledge aimed at this goal of better therapeutics, such as more specific and effective medications with fewer side effects.
The studies were led, respectively, by Drs. Pablo V. Gejman of NorthShore University HealthSystem (MGS, the Molecular Genetics of Schizophrenia collaboration), Pamela Sklar of the Broad Institute (ISC, the International Schizophrenia Consortium), and Kari Stefansson of deCODE Genetics (SGENE, the Schizophrenia Gene consortium).
The MGS study was supported by the National Institute of Mental Health (multiple grants), the Paul Michael Donovan Charitable Foundation, NorthShore University HealthSystem the National Alliance for Research on Schizophrenia and Depression, the Genetic Association Information Network (GAIN, and the National Center for Research Resources
About NorthShore University HealthSystem
Located in Chicago's northern suburbs, NorthShore University HealthSystem (formerly Evanston Northwestern Healthcare) is an academic health system affiliated with the University of Chicago’s Pritzker School of Medicine. Our integrated delivery system includes Evanston (founded in 1891), Glenbrook, Highland Park, and Skokie Hospitals as well as the NorthShore Medical Group, Research Institute, and Foundation. NorthShore has annual revenues of $1.5 billion and a staff of more than 8,000. The fully integrated health system has significant capabilities in a wide spectrum of clinical programs, including cancer, heart, orthopedics, high-risk maternity, and pediatrics. NorthShore is a national leader in the implementation of innovative technologies, including electronic medical records.
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