Biol Psychiat：免疫系统功能底下是患精神分裂症潜在风险因素

一项新的研究进一步发现，参与免疫系统的功能基因组区域，主要组织相容性复合体（MHC），参与了调控精神分裂症的遗传易感性。

精神分裂症是其中最常见的精神疾病之一。精神分裂症的风险约80％是来自遗传，确定其中遗传变异有助于降低精神分裂症的风险，但一直进展缓慢。在这项最新研究识别影响免疫系统功能的变种基因的研究中，研究人员证实某些功能基因组区域可能会导致遗传精神分裂症的风险增加。

两个大型国际合作组织的科学家--威康信托基金会病例控制协会和爱尔兰精神分裂症基因组学联盟完成了这项新的研究。他们首先对600多万名精神分裂症患者和来自爱尔兰的健康对照组的遗传变异情况进行了扫描。这使他们能够得到与精神分裂症相关性最强的基因变种名单。然后，他们对一个独立样本包括13195名精神分裂症患者和31,021来自世界各地的健康人群进行了类似的工作。

他们的研究结果进一步证实了MHC基因在精神分裂症易感性中发挥作用。都柏林大学Aiden Corvin博士评论说：研究已经证实了MHC位点的等位基因对精神分裂症的特定风险，这是参与调控免疫系统的功能基因组区域是精神分裂症遗传风险的关键证据。

这些基因的发现也突出了我们在免疫对精神分裂症的生物学作用中是一片空白。精神分裂症患者的免疫学研究，阐明免疫系统基因对精神分裂症的贡献将是精神分裂症研究一个重要的方向。

与精神分裂相关的拓展阅读：

• Biological Psych：精神分裂症风险基因和大麻依赖风险相关  
• Pharmacol Biochem Behav：研究发现氯氮平和奥氮平抗精神分裂作用机制
• BMJ Open：精神分裂症与躯体疾病共病相关
• EPA 2013：吸食大麻与精神分裂症较严重相关
• Biol Psychiatry：TMS可改善精神分裂症患者的记忆 更多信息请点击：有关精神分裂更多资讯

Genome-Wide Association Study Implicates HLA-C*01:02 as a Risk Factor at the Major Histocompatibility Complex Locus in Schizophrenia

Background We performed a genome-wide association study (GWAS) to identify common risk variants for schizophrenia.

Methods The discovery scan included 1606 patients and 1794 controls from Ireland, using 6,212,339 directly genotyped or imputed single nucleotide polymorphisms (SNPs). A subset of this sample (270 cases and 860 controls) was subsequently included in the Psychiatric GWAS Consortium-schizophrenia GWAS meta-analysis.

Results One hundred eight SNPs were taken forward for replication in an independent sample of 13,195 cases and 31,021 control subjects. The most significant associations in discovery, corrected for genomic inflation, were (rs204999, p combined = 1.34 × 10?9 and in combined samples (rs2523722 p combined = 2.88 × 10?16) mapped to the major histocompatibility complex (MHC) region. We imputed classical human leukocyte antigen (HLA) alleles at the locus; the most significant finding was with HLA-C*01:02. This association was distinct from the top SNP signal. The HLA alleles DRB1*03:01 and B*08:01 were protective, replicating a previous study.

Conclusions This study provides further support for involvement of MHC class I molecules in schizophrenia. We found evidence of association with previously reported risk alleles at the TCF4, VRK2, and ZNF804A loci.