| 1 | Gene 2013 Aug 525: 107-15 |
|---|---|
| PMID | 23644028 |
| Title | 通路分析的全基因组协会iation study in schizophrenia. |
| Abstract | The aim of this study was to identify the candidate single nucleotide polymorphisms (SNPs) and candidate mechanisms that contribute toschizophreniasusceptibility and to generate a SNP to gene to pathway hypothesis using an analytical pathway-based approach. We usedschizophreniaGWAS data of the genotypes of 660,259 SNPs in 1378 controls and 1351 cases of European descent after quality control filtering. ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis was applied to theschizophreniaGWAS dataset. The first stage involved the pre-selection of candidate SNPs by linkage disequilibrium analysis and the functional SNP annotation of the most significant SNPs found. The second stage involved the annotation of biological mechanisms for the pre-selected candidate SNPs using improved-gene set enrichment analysis. ICSNPathway analysis identified fifteen candidate SNPs, ten candidate pathways, and nine hypothetical biological mechanisms. The most strongly associated potential pathways were as follows. First, rs1644731 and rs1644730 to RDH8 to estrogen biosynthetic process (p<0.001, FDR<0.001). The genes involved in this pathway are RDH8 and HSD3B1 (p<0.05). All-trans-retinol dehydrogenase (RDH8) is a visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol in the presence of NADPH. The chemical reactions and pathways involved result in the formation of estrogens, which are C18 steroid hormones that can stimulate the development of female sexual characteristics. Second, rs1146031 to ACVR1 to mesoderm formation and activin binding (p<0.001, FDR=0.032, 0.034). Two of 15 candidate genes are known genes associated withschizophrenia: KCNQ2 and APOL2. One of the 10 candidate pathways, estrogen biosynthetic process, is known to be associated withschizophrenia(p<0.001, FDR<0.001). However, 13 of candidate genes (RDH8, ACVR1, PSMD9, KCNAB1, SLC17A3, ARCN1, COG7, STAB2, LRPAP1, STAB1,CXCL16, COL4A4, EXOSC3) and 9 of candidate pathways were novel. By applying ICSNPathway analysis toschizophreniaGWAS data, we identified candidate SNPs, genes like KCNQ2 and APOL2 and pathways involving the estrogen biosynthetic process may contribute toschizophreniasusceptibility. Further analyses are needed to validate the results of this analysis. |
| SCZ Keywords | schizophrenia |