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Schizophrenia Research Points to Rare Mutations

Structural variants more often found in genes involved in brain-development pathways

MONDAY, March 31 (HealthDay News) -- A variety of individually rare mutations affecting genes that play roles in neurodevelopmental pathways -- specific even to individuals or families -- may contribute to schizophrenia, according to research published online March 27 in Science.

Tom Walsh, Ph.D., of the University of Washington in Seattle, and colleagues conducted genomewide scans in 150 people with schizophrenia and 268 healthy controls. Cases were more than threefold more likely to have rare structural variants that deleted or duplicated at least one gene; cases with young onset were more than fourfold more likely to have these variants. Virtually every structural mutation was different. Genes disrupted by structural variants in cases were excessively represented in brain-development pathways, but weren't over-represented in any pathway in controls.

In another series of 83 cases of childhood-onset disease and 77 controls, the investigators found that cases were significantly more likely than controls to have rare structural variants impacting genes (odds ratio 2.57).

"In two independent cohorts, we found structural variants impacting genes to be more common among individuals with schizophrenia than among controls. Our design does not prove the involvement with the illness of any specific variant, or even the involvement of any specific gene. Rather, these results suggest that schizophrenia can be caused by rare mutations that disrupt genes in pathways of neuronal development and regulation. This model suggests a new approach to gene discovery for schizophrenia, and likely for other psychiatric disorders," the authors write.

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