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

被引:175
作者
Green, EK
Raybould, R
Macgregor, S
Gordon-Smith, K
Heron, J
Hyde, S
Grozeva, D
Hamshere, M
Williams, N
Owen, MJ
O'Donovan, MC
Jones, L
Jones, I
Kirov, G
Craddock, N
机构
[1] Cardiff Univ, Dept Psychol Med, Cardiff CF14 4XN, Wales
[2] Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, Wales
[3] Univ Birmingham, Queen Elizabeth Psychiat Hosp, Dept Psychiat, Div Neurosci, Birmingham, W Midlands, England
关键词
D O I
10.1001/archpsyc.62.6.642
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
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 10 11 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 5 73 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% Cl, 0.921.61). In the bipolar cases with predominantly mood-incongruent psychotic features (n=193), the effect was greater (OR, 1.71; 95% Cl, 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% Cl, 0.54-5.01). Conclusions: Our findings suggest that neuregulin I 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.
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页码:642 / 648
页数:7
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