| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Apr 147: 343-50 |
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| PMID | 18092318 |
| Title | Comprehensive evaluation of positional candidates in the IL-18 pathway reveals suggestive associations with schizophrenia and herpes virus seropositivity. |
| Abstract | Interactions between genetic variation and environmental factors have been invoked inschizophreniagenesis, but pathways linking them are uncertain. We used a pathway-oriented approach to evaluate six genes mediatingIL18function (IL-18,IL18BP,IL18R1,IL18RAP, IL12B, and IL12A). The first five are also localized to regions previously linked withschizophrenia. Fifty-four representative tag SNPs were selected from comprehensive sequence data and genotyped in 478 patients withschizophrenia/schizoaffective disorder (DSM IV criteria) and 501 unscreened control individuals. Exposure to three herpes viruses previously suggested as risk factors forschizophreniawas estimated simultaneously among the cases. Five SNPs in four genes were associated withschizophrenia,特别是rs2272127 atIL18RAP (P = 0.0007, odds ratio for C allele 1.49, 95% CI: 1.18-1.87; P = 0.03 following correction for multiple comparisons). Exploratory analysis revealed that rs2272127 was also associated with herpes simplex virus 1 (HSV1) seropositivity in cases (P = 0.04, OR for G allele 1.58, 95% CI: 1.04-2.39). Similar patterns were observed at another correlated SNP (rs11465702, P = 0.005 and 0.006, respectively for associations withschizophreniaand HSV1 seropositivity). We suggest plausible, testable hypotheses linking IL-18 signaling and HSV1 inschizophreniapathogenesis. |
| SCZ Keywords | schizophrenia |
| 2 | J Psychiatr Res 2016 Mar 74: 10-6 |
| PMID | 26736035 |
| Title | Potential involvement of the interleukin-18 pathway in schizophrenia. |
| Abstract | Accumulating evidence implicates inflammatory cytokines in the development of psychiatric disorders, includingschizophrenia(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. We 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 ofIL18R1 rs1035130 with SZ in an independent sample of 1957 adult patients and 1509 controls. We compared expression levels ofIL18,IL18R1 andIL18RAP 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 forIL18R1 rs1035130. In the discovery stage, we detected association signals within twoIL18pathway genes,IL18R1 andIL18RAP, with the most significant marker beingIL18R1 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 ofIL18andIL18R1 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. Our findings suggest the alteration ofIL18pathway may contribute to the psychopathology of SZ. |
| SCZ Keywords | schizophrenia |