WASHINGTON, DC—Three genome-wide studies have collectively identified an array of genetic variations that may account for as much as one-third of the genetic risk for schizophrenia. The trio of studies—collectively the largest genome-wide association studies to date—were conducted by three schizophrenia genetics research consortia, each funded in part by the National Institute of Mental Health. The three consortia shared their results with each other, creating a combined pool of 8,014 cases and 19,090 controls from which to perform meta analyses. One of the studies traced schizophrenia and bipolar disorder, in part, to the same chromosomal area. The studies’ results were published online in the journal Nature.

All three studies implicate an area of Chromosome 6 (6p22.1), which is known to harbor genes involved in immunity and controlling how and when genes turn on and off. This association might help to explain how environmental factors affect risk for schizophrenia. For example, there are hints of autoimmune involvement in schizophrenia, such as evidence that offspring of mothers with influenza while pregnant have a higher risk of developing the illness.

Among sites showing the strongest associations with schizophrenia was a suspect area on Chromosome 22 and more than 450 variations in the suspect area on Chromosome 6. Statistical simulations confirmed that the findings could not have been accounted for by a handful of common gene variants with large effect or just rare variants. This involvement of many common gene variants suggests that schizophrenia in different people might ultimately be traceable to distinct disease processes, explained researchers. However, most of the genetic contribution to schizophrenia, which is estimated to be at least 70% heritable, remains unknown.

The Molecular Genetics of Schizophrenia consortium study pinpointed an association between schizophrenia and genes in the Chromosome 6 region that code for cellular components that control when genes turn on and off. For example, one of the strongest associations was seen in the vicinity of genes for histones—proteins that affix a molecular clamp on a gene’s turning on in response to the environment. Genetically rooted variation in the functioning of such regulatory mechanisms could help to explain the environmental component repeatedly implicated in schizophrenia risk, researchers said. The same study also found an association between schizophrenia and a genetic variation on Chromosome 1 (1p22.1), which has been implicated in multiple sclerosis, an autoimmune disorder.

Another of the three studies, one conducted by the SGENE consortium, pinpointed a site of variation in the suspect Chromosome 6 region that could implicate processes related to immunity and infection. It also found significant evidence of association with variation on Chromosomes 11 and 18 that could help account for the thinking and memory deficits of schizophrenia.

According to NIMH, these discoveries could eventually lead to finding multi-gene signatures or biomarkers for severe mental disorders. As more is learned about the implicated gene pathways, it may be possible to sort out what’s shared by, or unique to, schizophrenia and bipolar disorder.

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