精神分裂症注意及执行功能的全基因组关联分析

A genome-wide association study of attention and executive function in patients with schizophrenia

目的以认知功能中的注意和执行功能为内表型，运用全基因组关联分析策略寻找精神分裂症的相关基因。方法采用连线测验评估98例精神分裂症患者（患者组）和60名正常对照者（对照组）的注意和执行功能；使用IlluminaHumanHap660 BeadArray进行基因分型，有464301个单核苷酸多态性（single nucleotide polymorphisms，SNPs）通过质量控制用于本研究的关联分析；以SNPs为分析因素，年龄、性别和受教育年限为协变量，连线测验结果为数量性状，用PLINK软件分别对患者组和对照组作主效应分析。结果PTPRC基因的2个SNPs位点与精神分裂症的注意功能缺损有关联（rs3767742，P：1．83×10^-5；rs12409128，P=4．50×10^-6）；UGT2A1、VPS13A和CNTN13个基因内的10个SNPs位点与精神分裂症的执行功能缺陷有关联（rs10011630，P=5．88×10^-8；rs4148284，P：5．88×10^-8；rs4148283，P=5．88×10^-8；rs4148282，P=5．88×10^-8；rs7030802，P=2．91x10^-6；rs12343395，P=4．30×10^-6rs7035855，P=2．91×10^-6；rs7039192，P=2．91×10^-6rs12316203，P=2．91×10^-6；rs13328933，P：2．91×10^-6），且这些位点与个体患精神分裂症的状态存在交互作用。结论PTPRC、UGT2A1、VPS13A和CNTN1可能是精神分裂症的易感基因，尚待进一步验证。

Objective The study used genome-wide association study （GWAS） to explore related genes for schizophrenia with attention and executive function of cognition as endophenotypes. Methods Trial making tests were used to assess attention and executive function in 98 schizophrenia patients and 60 normal controls. HumanHap660 BeadArray was used to genotype and 464 301 SNPs passed quality control checks. Taking SNPs as analytic factors, age, gender and education years as covariates, trial making tests as quantitative traits, the study used PLINK software to complete main effect analyses of the case group and the control group. Results Two SNPs residing on PTPRC were associated with attention deficit（ rs3767742 ,P = 1.83 × 10-5 ; rs12409128, P = 4. 50 × 10-6 ） ; 10 SNPs which locate in UGT2A1, VPS13A and CNTN1 respectively were associated with executive function deficit（ rs10011630, P = 5.88 × 10 -8 ; rs4148284, P = 5.88 × 10-8 ; rs4148283, P = 5.88 × 10-8 ; rs4148282, P = 5.88 × 10-8 ; rs7030802, P = 2. 91 × 10-6 ; rs12343395, P = 4. 30 × 10 -6 ; rs7035855, P = 2. 91 ×10 -6 ; rs7039192, P = 2. 91 × 10 -6 ; rs12316203, P = 2.91 × 10-6 ; rs13328933, P = 2.91 × 10-6 ）, moreover, these SNPs had interaction with individual schizophrenia state. Conclusions PTPRC, UGT2A1, VPS13A and CNTN1 may be the susceptibility genes for schizophrenia that merit further investigation.