RT Journal
A1 Green EK, Raybould R, Macgregor S, et al
T1 OPeration of the schizophrenia susceptibility gene, neuregulin 1, across traditional diagnostic boundaries to increase risk for bipolar disorder
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2005
FD June 1
VO 62
IS 6
SP 642
OP 648
DO 10.1001/archpsyc.62.6.642
UL http://dx.doi.org/10.1001/archpsyc.62.6.642
AB 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.