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An association study of the neuregulin 1 gene, bipolar affective disorder and psychosis.

机译：神经调节蛋白1基因，双相情感障碍与精神病的关联研究。

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OBJECTIVE: As evidence of partial aetiological overlap between bipolar affective disorder and schizophrenia is accumulating, it is important to determine whether genes implicated in the aetiology of schizophrenia play a role in bipolar disorder, and vice versa. As the neuregulin 1 (NRG1) gene has been associated with schizophrenia, we set out to investigate whether it is also associated with bipolar affective disorder, using a sample from Scotland, UK. METHODS: We tested four single nucleotide polymorphisms (SNPs), SNP8NRG221533 (rs35753505), SNP8NRG241930, SNP8NRG243177 (rs6994992) and SNPNRG222662 (rs4623364) for allelic and haplotypic association with bipolar disorder and the presence of psychotic or mood-incongruent psychotic features. RESULTS: We found nominal allele-wise significant association (P = 0.02) for SNP8NRG221533, with the T allele being overrepresented in cases. This is the opposite allelic association to the original association study where the C allele was associated with schizophrenia. Allele-wise significance increased when we tested for association with the subgroups of bipolar disorder with psychotic features (chi2 = 8.53; P = 0.003; odds ratio = 1.49) and, more specifically, with mood-incongruent psychotic features (chi2 = 7.13; P = 0.008; odds ratio = 1.57). Furthermore, both these subphenotypes were significantly associated with the SNP8NRG221533(T)-SNP8NRG241930(G) haplotype (chi2 = 11.94, global P = 0.027 and chi2 = 11.88, global P = 0.019, respectively) and with the SNP8NRG221533(T)-SNP8NRG222662(C)-SNP8NRG241930(G) haplotype (chi2 = 19.98, global P = 0.009) in case of the broader subphenotype of psychotic bipolar. CONCLUSION: This study supports the hypothesis that NRG1 may play a role in the development of bipolar disorder, especially in psychotic subtypes, albeit with different alleles to previous association reports in schizophrenia and bipolar disorder.
机译：目的：随着双相情感障碍和精神分裂症之间部分病因学重叠的积累，确定与精神分裂症病因相关的基因是否在双相情感障碍中起作用，反之亦然，这一点很重要。由于神经调节蛋白1（NRG1）基因已与精神分裂症相关，我们开始使用来自英国苏格兰的样本调查其是否也与双相情感障碍有关。方法：我们测试了四个单核苷酸多态性（SNP），SNP8NRG221533（rs35753505），SNP8NRG241930，SNP8NRG243177（rs6994992）和SNPNRG222662（rs4623364）与双相情感障碍的等位基因和单倍型关联以及是否存在精神病或与情绪无关的精神病特征。结果：我们发现SNP8NRG221533的名义等位基因与智商之间的显着相关性（P = 0.02），其中T等位基因在病例中过分表达。这是与C等位基因与精神分裂症相关的原始关联研究相反的等位基因关联。当我们测试与患有精神病性特征的双相情感障碍亚组之间的关联时，等位基因意义显着性增加（chi2 = 8.53; P = 0.003;优势比= 1.49），更具体地说，与情绪不相容的精神病性特征（chi2 = 7.13; P = 0.008;优势比= 1.57）。此外，这两个亚表型均与SNP8NRG221533（T）-SNP8NRG241930（G）单倍型显着相关（分别为chi2 = 11.94，全局P = 0.027和chi2 = 11.88，全局P = 0.019）以及SNP8NRG221533（T）-SNP8NRG222662 （C）-SNP8NRG241930（G）单倍型（chi2 = 19.98，全局P = 0.009），是精神病性双极的较宽亚表型。结论：本研究支持以下假设：NRG1可能在双相情感障碍的发展中起作用，尤其是在精神病亚型中，尽管与先前有关精神分裂症和双相情感障碍的相关报道具有不同的等位基因。

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