NorthShore University HealthSystem Researcher Leads International Collaboration to Find Five New Genetic Loci Associated with Schizophrenia

Evanston, IL – September 21, 2011 – Pablo V. Gejman, M.D., Director of the NorthShore University HealthSystem (NorthShore) Center for Psychiatric Genetics led an international consortium conducting a genome-wide association study (GWAS) on schizophrenia. The researchers found five novel genetic variants that increase the susceptibility to schizophrenia. The findings are reported in the September 18, 2011 advance online edition of the journal Nature Genetics.

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 current treatments work well. There are multiple factors that increase the risk for schizophrenia, of which genetic factors are the strongest in the aggregate, though not precisely identified yet.

“This research highlights the need for a better understanding of the pathways leading to schizophrenia to enable development of better treatments,” said Dr. Gejman.

“Schizophrenia is largely a genetic disorder, though a complex one, and people who have close family members with schizophrenia are somewhat more likely to get this chronic, debilitating brain disorder,” said Alan R. Sanders, M.D., a collaborator also at NorthShore. “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.”

The publication is entitled “Genome-wide association study identifies five new schizophrenia loci” and is published under the byline of The Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium, or PGC-SZ. Formed in 2007, the PGC is the largest consortium ever in psychiatry. Over 250 researchers from more than 20 countries collaborated in an unparalleled spirit of cooperation to advance knowledge of the genetic causes of mental illness. Crucial to the project’s success was the willingness of many groups to share genetic data from tens of thousands of patients collected over many years. Numerous European, American, and Australian entities funded the research, and the US National Institute of Mental Health provided funds for coordination of the consortium.

The PGC-SZ collaboration was comprised of 17 research groups from the US, Europe and Australia, examining the role of common genetic variation in schizophrenia in an experiment of exceptional size: the discovery sample included almost 22,000 individuals of European ancestry, and the replication sample had 30,000 additional subjects. Seven loci that increase the susceptibility to schizophrenia were detected, five of them, novel (on chromosomes 1p21.3, 2q32.3, 8p23.2, 8q21.3, and 10q24.32-q24.33). Another two previously implicated loci were confirmed (on chromosomes 6p21.32-p22.1 and 18q21.2). The strongest novel finding was at microRNA 137 (MIR137), a regulator of neuronal development. Four other schizophrenia loci detected in this study contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a novel etiologic mechanism in schizophrenia. The strongest finding was at chromosome 6p21.32-p22.1, at the extended MHC region.

“The MHC region includes a histone gene cluster (protein “spools” around which DNA wraps and affects 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.

Additionally, in a joint analysis with the PGC bipolar disorder sample led by Dr. Pamela Sklar and published jointly in the same journal issue, three loci (CACNA1C, ANK3, and the ITIH3/4 region) achieved genome-wide significance.

“These studies show that there are numerous common variants increasing risk for schizophrenia, albeit representing small individual effects, many probably acting in the aggregate. Our challenge is to discover the biological mechanisms that underlie the statistical associations,” Dr. Gejman added.

The NorthShore team expects to continue to generate knowledge with a goal of developing better therapeutics, such as more specific and effective medications with fewer side effects.

About NorthShore University HealthSystem

Headquartered in Evanston, Illinois, NorthShore University HealthSystem (NorthShore) is a comprehensive, fully integrated, healthcare delivery system that serves the Chicago region. The system includes four hospitals in Evanston, Glenview, Highland Park, and Skokie. NorthShore employs approximately 9,000 and has 2,400 affiliated physicians, including a 700+ physician, multispecialty group practice with over 75 office locations. Further, NorthShore supports teaching and research as the principal teaching affiliate for the University of Chicago Pritzker School of Medicine.

The NorthShore Research Institute focuses on clinical and translational research, including leadership in outcomes research and clinical trials. The NorthShore University HealthSystem Foundation is the primary philanthropic entity of NorthShore. The Foundation raises charitable contributions and engages volunteer friends in support of NorthShore’s ongoing mission to preserve and improve human life.

NorthShore has significant capabilities in a wide spectrum of clinical programs, including cancer, heart, orthopaedics, high-risk maternity, pediatrics and neurosciences. NorthShore is a Magnet recognized organization, the only one in Illinois designated as a system to receive this prestigious honor that demonstrates excellence in nursing and high standards in patient care. NorthShore is a national leader in the implementation of innovative technologies, including electronic medical records (EMR). In 2003, NorthShore was among the first in the country to successfully launch a system-wide EMR with demonstrable benefits in quality, safety, efficiency and service to patients. NorthShore has been recognized by multiple national organizations for this notable achievement.

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Contact:
Colette Urban
Director, Public Relations
(847) 570-3144
CUrban@northshore.org

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