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Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder

Green, Elaine Karen, Raybould, Rachel, Macgregor, Stuart, Gordon-Smith, Katherine Mary, Heron, Jess, Hyde, Sally, Grozeva, Detelina Valentinova, Hamshere, Marian Lindsay, Williams, Nigel Melville, Owen, Michael John, O'Donovan, Michael Conlon, Jones, Lisa Anne, Jones, Ian Richard, Kirov, George and Craddock, Nicholas John 2005. Operation of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder. Archives of general psychiatry 62 (6) , pp. 642-648. 10.1001/archpsyc.62.6.642

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Abstract

Context Family and twin data suggest that, in addition to susceptibility genes specific for bipolar disorder or schizophrenia, genes exist that contribute to susceptibility across the traditional kraepelinian divide. Several studies have provided evidence that variation at the neuregulin 1 (NRG1) gene on chromosome 8p12 influences susceptibility to schizophrenia. The most consistent finding has been that one particular haplotype (the "core" haplotype) is overrepresented in cases compared with control subjects. Objective To investigate the possible role of NRG1 in bipolar disorder. Design Genetic case-control association analysis. Setting Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. Participants Five hundred twenty-nine patients with DSM-IV bipolar I disorder and 1011 controls from the United Kingdom (100% white). Methods We genotyped the markers constituting the NRG1 core haplotype in cases and controls and reanalyzed our existing data from 573 DSM-IV schizophrenia cases with this larger set of controls. Results We found a significant difference in haplotype distribution between bipolar cases and controls globally (P = .003) and specifically for the core haplotype. Frequencies were 10.2% for bipolar cases and 7.8% for controls (effect size, as measured by odds ratio [OR], 1.37; 95% confidence interval [CI], 1.03-1.80; P = .04). The effect size in our bipolar sample was similar to that in our schizophrenia sample (OR, 1.22; 95% CI, 0.92-1.61). In the bipolar cases with predominantly mood-incongruent psychotic features (n = 193), the effect was greater (OR, 1.71; 95% CI, 1.29-2.59; P = .009), as was the case in the subset of schizophrenia cases (n = 27) who had experienced mania (OR, 1.64; 95% CI, 0.54-5.01). Conclusions Our findings suggest that neuregulin 1 plays a role in influencing susceptibility to bipolar disorder and schizophrenia and that it may exert a specific effect in the subset of functional psychosis that has manic and mood-incongruent psychotic features.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: American Medical Association
ISSN: 0003990X
Related URLs:
Last Modified: 04 Jun 2017 01:34
URI: http://orca.cf.ac.uk/id/eprint/567

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