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| |  Schizophrenia and Bipolar Disorder Share Genetic Roots, Researchers Find BETHESDA, Md -- July 3, 2009 -- A trio of genome-wide studies have pinpointed a vast array of genetic variation that cumulatively may account for at least one third of the genetic risk for schizophrenia. One of the studies traced schizophrenia and bipolar disorder, in part, to the same chromosomal neighborhoods. “These new results recommend a fresh look at our diagnostic categories,” said Thomas R. Insel, MD, National Institute of Mental Health (NIMH), Bethesda, Maryland. “If some of the same genetic risks underlie schizophrenia and bipolar disorder, perhaps these disorders originate from some common vulnerability in brain development.” Three schizophrenia genetics research consortia report separately on their genome-wide association studies in the July 1 online issue of the journal Nature. However, the International Schizophrenia (ISC) and Molecular Genetics of Schizophrenia (MGS) consortia shared their results, making possible meta-analyses of a combined sample totaling 8,014 cases and 19,090 controls. All 3 studies implicate an area of Chromosome 6 (6p22.1), which is known to harbour genes involved in immunity and controlling how and when genes turn on and off. This hotspot of association might help to explain how environmental factors affect risk for schizophrenia. 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, say the researchers. There was substantial overlap in the genetic risk for schizophrenia and bipolar disorder that was specific to mental disorders. Researchers saw no association between the suspect gene variants and half a dozen common non-psychiatric disorders. Still, most of the genetic contribution to schizophrenia, which is estimated to be at least 70% heritable, remains unknown. The MGS consortium 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 proteins called histones that slap 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. The MGS study also found an association between schizophrenia and a genetic variation on Chromosome 1 (1p22.1) which has been implicated in multiple sclerosis. “Our study results spotlight the importance not only of genes, but also the little-known DNA sequences between genes that control their expression,” said Pablo Gejman, MD, NorthShore University HealthSystem Research Institute, Evanston, Illiniois. “Advances in biotechnology, statistics, population genetics, and psychiatry, in combination with the ability to recruit large samples, made the new findings possible.” The SGENE consortium study 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. The new findings could eventually lead to 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, the researchers said. SOURCE: National Institutes of Health
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