Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder.
Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder.
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DOI：
10.1097/ypg.0b013e32835bd5f1
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发表时间：
2013-02
影响因子：
0.9
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Jackson KJ;Fanous AH;Chen J;Kendler KS;Chen X
精神分裂症患者的吸烟率明显高于一般人群。这种并发症的潜在机制尚不清楚。一种假设是，有共同的遗传因素，易患尼古丁依赖（ND）和精神分裂症。为了研究这一假设，我们研究了15 q25基因簇与精神分裂症和双相情感障碍的关联，该基因簇是迄今为止与ND和吸烟行为有关的最重要的候选区域。选择15 q25基因簇中的五个变体（rs 951266，rs 16969968，rs 1051730，rs 8040868和rs 17477223）来测试与精神分裂症诊断，双相情感障碍诊断和精神分裂症阴性症状存在的相关性。使用解剖学上可获得的死后脑表达数据分析变体对15 q25基因表达的影响。一项荟萃分析揭示了与精神分裂症和双相情感障碍风险相关的四个标志物（rs 951266、rs 16969968、rs 8040868和rs 17477223）以及与精神分裂症阴性症状的存在相关的四个标志物（rs 951266、rs 1051730、rs 8040868和rs 17477223）。这些关联与ND的关联方向相同。基因表达分析表明，rs 1051730变异体基因型与脑和外周血单核细胞中CHRNA 5表达之间存在关联，与脑中rs 16969968和rs 17477223变异体之间存在关联。15 q25基因簇中的变异与精神分裂症/双相情感障碍、精神分裂症阴性症状的风险相关，并影响脑和外周血单核细胞中CHRNA 5的表达。这些结果与精神分裂症、ND和双相情感障碍存在共同遗传机制的观点一致。
Rates of tobacco smoking are significantly higher in patients with schizophrenia compared with the general population. The underlying mechanism for this comorbidity is unclear. One hypothesis is that there are common genetic factors that predispose to both nicotine dependence (ND) and schizophrenia. To investigate this hypothesis, we examined the association of the 15q25 gene cluster, the most significant candidate region to date implicated in ND and smoking behavior, with schizophrenia and bipolar disorder. Five variants in the 15q25 gene cluster (rs951266, rs16969968, rs1051730, rs8040868, and rs17477223) were selected to test for association with schizophrenia diagnosis, bipolar disorder diagnosis, and the presence of negative symptoms of schizophrenia. Effects of the variants on 15q25 gene expression were analyzed using publically available postmortem brain expression data. A meta-analysis revealed four markers associated with risk for schizophrenia and bipolar disorder (rs951266, rs16969968, rs8040868, and rs17477223), and with the presence of negative symptoms of schizophrenia (rs951266, rs1051730, rs8040868, and rs17477223). The associations were in the same direction as that found for ND. Gene expression analysis indicated an association between genotypes of the rs1051730 variant and CHRNA5 expression in brain and peripheral blood mononuclear cells, and with the rs16969968 and rs17477223 variants in brain. Variants in the 15q25 gene cluster are associated with risk for schizophrenia/bipolar illness, negative symptoms of schizophrenia, and influence CHRNA5 expression in the brain and peripheral blood mononuclear cells. These results are consistent with the notion that there are genetic mechanisms common to schizophrenia, ND, and bipolar disorder.