Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, PR China.
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:50-54. doi: 10.1016/j.pnpbp.2017.10.003. Epub 2017 Oct 9.
Schizophrenia is a serious mental disease with high heritability. To better understand the genetic basis of schizophrenia, we conducted a large scale integrative analysis of genome-wide association study (GWAS) and expression quantitative trait loci (eQTLs) data. GWAS summary data was derived from a published GWAS of schizophrenia, containing 9394 schizophrenia patients and 12,462 healthy controls. The eQTLs dataset was obtained from an eQTLs meta-analysis of 5311 subjects, containing 923,021 cis-eQTLs for 14,329 genes and 4732 trans-eQTLs for 2612 genes. Genome-wide single gene expression association analysis was conducted by SMR software. The SMR analysis results were further subjected to gene set enrichment analysis (GSEA) to identify schizophrenia associated gene sets. SMR detected 49 genes significantly associated with schizophrenia. The top five significant genes were CRELD2 (p value=1.65×10), DIP2B (p value=3.94×10), ZDHHC18 (p value=1.52×10) and ZDHHC5 (p value=7.45×10), C11ORF75 (p value=3.70×10). GSEA identified 80 gene sets with p values <0.01. The top five significant gene sets were COWLING_MYCN_TARGETS (p value <0.001) and CHR16P11 (p value <0.001), ACTACCT_MIR196A_MIR196B (p value=0.002), CELLULAR_COMPONENT_DISASSEMBLY (p value=0.002) and GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN (p value=0.002). Our results provide useful information for revealing the genetic basis of schizophrenia.
精神分裂症是一种具有高遗传性的严重精神疾病。为了更好地了解精神分裂症的遗传基础，我们对全基因组关联研究（GWAS）和表达数量性状基因座（eQTLs）数据进行了大规模综合分析。GWAS 汇总数据来自一项已发表的精神分裂症 GWAS，包含 9394 名精神分裂症患者和 12462 名健康对照。eQTLs 数据集来自于 5311 名受试者的 eQTLs 荟萃分析，包含 14329 个基因的 923021 个顺式-eQTLs 和 2612 个基因的 4732 个反式-eQTLs。通过 SMR 软件进行全基因组单基因表达关联分析。SMR 分析结果进一步进行基因集富集分析（GSEA），以鉴定与精神分裂症相关的基因集。SMR 检测到 49 个与精神分裂症显著相关的基因。前五个显著基因是 CRELD2（p 值=1.65×10）、DIP2B（p 值=3.94×10）、ZDHHC18（p 值=1.52×10）和 ZDHHC5（p 值=7.45×10），C11ORF75（p 值=3.70×10）。GSEA 鉴定到 80 个 p 值<0.01 的基因集。前五个显著基因集是 COWLING_MYCN_TARGETS（p 值<0.001）和 CHR16P11（p 值<0.001）、ACTACCT_MIR196A_MIR196B（p 值=0.002）、CELLULAR_COMPONENT_DISASSEMBLY（p 值=0.002）和 GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN（p 值=0.002）。我们的结果为揭示精神分裂症的遗传基础提供了有用的信息。
