Potential involvement of the interleukin-18 pathway in schizophrenia
Potential involvement of the interleukin-18 pathway in schizophrenia
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IL-18 通路可能参与精神分裂症
DOI：
10.1016/j.jpsychires.2015.12.013
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发表时间：
2016
影响因子：
4.8
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Xu Y;Yue W;Shugart YY;Yuan J;Wang G;Wang HZ;Lehrman B;Zhang F;Zhang D
越来越多的证据表明，炎症细胞因子与精神疾病（包括精神分裂症（SZ））的发展有关。IL-18是在免疫应答和神经发育中起重要作用的细胞因子之一。我们的目的是调查潜在的遗传改变的细胞因子系统的基础SZ.MethodsWe测试的关联遗传变异内的精氨酸-细胞因子受体相互作用（CCRI）途径与SZ，使用GWAS衍生的数据，涉及768名成年SZ患者和1348名对照，并在1957名成人患者和1509名对照的独立样本中复制了IL 18 R1 rs 1035130与SZ的关联。我们比较了一组青少年参与者（<18岁）外周血中IL 18，IL 18 R1和IL 18 RAP的表达水平，包括14名早发性SZ患者和13名健康对照。此外，我们还进行了一个顺式eQTL定位，（表达数量性状基因座）和顺式mQTL结果在发现阶段，我们检测到IL 18信号通路基因IL 18 R1和IL 18 RAP之间的关联信号，其中最显著的标记是IL 18 R1 rs 1035130（P = 1.84E-7，OR = 0.70）。在验证阶段，我们发现rs 1035130与SZ相关（P = 0.028，OR = 0.89）。SZ患者外周血IL 18和IL 18 R1的表达与13名对照相比发生了变化。此外，cis-QTL分析表明，rs 1035130与一个eQTL和5个mQTLs.ConclusionOur研究结果表明，IL 18通路的改变可能有助于SZ的精神病理学。
ObjectiveAccumulating evidence implicates inflammatory cytokines in the development of psychiatric disorders, including schizophrenia (SZ). IL-18 is one of cytokines that plays a crucial role in immune response and neurodevelopment. We aimed to investigate potential genetic alterations of the cytokine system underpinning SZ.MethodsWe tested the association of genetic variants within the cytokine–cytokine receptor interaction (CCRI) pathway with SZ, using GWAS-derived data involving 768 adult SZ patients and 1348 controls, and replicated the association of IL18R1 rs1035130 with SZ in an independent sample of 1957 adult patients and 1509 controls. We compared expression levels of IL18, IL18R1 and IL18RAP in peripheral blood of a cohort of adolescent participants (<18 years), including 14 early-onset SZ patients and 13 healthy controls. Furthermore, we carried out a cis-eQTL (expression Quantitative Trait Loci) and a cis-mQTL (Methylation Quantitative Trait Loci) analysis for IL18R1 rs1035130.ResultsIn the discovery stage, we detected association signals within two IL18 pathway genes, IL18R1 and IL18RAP, with the most significant marker being IL18R1 rs1035130 (P = 1.84E-7, OR = 0.70). In the validation stage, we found rs1035130 was associated with SZ (P = 0.028, OR = 0.89). Expressions of IL18 and IL18R1 were altered in blood of SZ patients compared with 13 controls. Furthermore, cis-QTL analyses indicated that rs1035130 was associated with an eQTL and 5 mQTLs.ConclusionOur findings suggest the alteration of IL18 pathway may contribute to the psychopathology of SZ.