Schizophrenia linked to common genetic variations

by Poonam Singhal



Researchers has discovered that nearly a third of the genetic basis of schizophrenia may be attributed to the cumulative actions of thousands of common genetic variants.

Schizophrenia is a devastating mental disease, thought to be caused by the interaction of both genetic and environmental factors. Because there is no biochemical test that can identify the disorder, physicians rely upon the recognition of its symptoms - which can include auditory hallucinations and paranoia - in order to make their diagnosis.

Stanford University School of Medicine scientists have played a major role in an international effort that has shown, for the first time, that modern genetic technologies can solve the riddle of how gene variations lead to schizophrenia.

Researchers at Stanford and 14 other institutions carried out a study of common DNA variations throughout the genome, and then combined forces with two independent studies to complete a pooled analysis of 27,000 individuals. The largest genetic differences between the study participants with and without schizophrenia were found on a stretch of chromosome 6 containing numerous genes associated with immune response (and some with other roles). This raises the possibility that immune function plays a role in schizophrenia.

The finding, published in the journal Nature, suggests that schizophrenia is much more complex than previously thought, and can arise not only from both rare genetic variants but also from a significant number of common ones.

In this study, Sullivan and other investigators in the Consortium used "genechip" technology to identify 30,000 genetic variants (single nucleotide polymorphisms or "SNPs") that were more common in 3,000 individuals with schizophrenia than in 3,000 comparison subjects without schizophrenia. This pattern was found in three separate samples of individuals with schizophrenia and two samples with bipolar disorder – indicating a previously unrecognized overlap between the two diseases. These risk variants were not present in patients with other non-psychiatric diseases, such as hypertension or diabetes.

"While our study finds a surprising number of genetic effects, we fully expect that future work will assemble them into meaningful pathways that will teach us about the biology of schizophrenia and bipolar disorder," says senior author Pamela Sklar, MD, PhD, associate director of the Department of Psychiatry and Center for Human Genetic Research at Massachusetts General Hospital (MGH) and a senior associate member of the Broad Institute of MIT and Harvard.

The researchers are also investigating how genes and environment interact to cause the disease. One additional finding of their study was the identification of the human leukocyte antigen (HLA) locus as a possible risk factor. Because this region plays an important role in immune response to infection, it could suggest that exposure to an infectious agent increases risk of developing psychiatric disease.


(Poonam Singhal -- sub-editor compiled and published Schizophrenia linked to common genetic variations at HealthNewsTrack on July 1, 2009 sourced from Stanford University Medical Center - http://med-www.stanford.edu/)

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