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Region of chromosome 22 linked to bipolar disorder, again
Same region may contain susceptibility gene(s) for schizophrenia
Edward R. Winstead

A genome-wide search for susceptibility genes in bipolar disorder has yielded a potential hotspot on chromosome 22. In addition to the chromosome 22 region, researchers found evidence of susceptibility genes for bipolar disorder on chromosomes 3, 5, 10, 13 and 21. The regions of chromosomes 22, 13, and 10 implicated here may also contain susceptibility genes for schizophrenia, according to published data.

Proof that bipolar disorder, or manic depression, and schizophrenia have susceptibility genes in common will require the identification of specific genes. But the researchers, led by John R. Kelsoe, of University of California, San Diego, are intrigued that the disorders might share risk factors—and that different mutations in the same gene might have different disease outcomes. Writing in Proceedings of the National Academies of Science, they cite data suggesting some degree of overlap between the disorders. The new scans, they note, raise the possibility that "the relationship between these two disorders may be more complex than previously thought."

The researchers analyzed the genomes of 164 subjects from 20 families that had been recruited in San Diego and Vancouver, British Columbia. The researchers used 443 DNA markers to track the inheritance of chromosome regions among affected and unaffected individuals, and a statistical analysis of the scan data yielded the potential hotspots. The strongest statistical evidence implicated chromosome 22.

Kelsoe and colleagues first reported a possible risk factor for bipolar disorder on chromosome 22 in 1997. That study involved 13 of the 20 families reported in the current study, which used more individuals and more DNA markers. To gain some independent confirmation of the findings, Kelsoe's group compared its data to scans involving 57 families from the Bipolar Disorder Genetics Initiative (from the US National Institutes of Mental Health). The findings were consistent with the current study, according to the researchers.

Different hypotheses about the role of genes in the development of bipolar disorder have been proposed. One theory says the risk for bipolar disorder is due to a few susceptibility genes; another says that many susceptibility genes contribute modestly to the risk for disease.

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Kelsoe, J.R. et al. A genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22. Proc Natl Acad Sci U S A 98, 585-590 (January 16, 2001).

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