Introduction: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We per- formed a meta-analysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews. Methods: We identifed articles by systematic searches of PubMed, PsycIn- fo, and ISI, and the reference lists of identifed studies. For each cytokine or chemokine polymorphism, we performed an allele- and genotype-wise meta-analysis, using a random efects model. Results: Twenty-one independent studies met the inclusion criteria, comprising polymorphisms for the IL1B, IL2, IL4, IL6, sIL6R, MCP1, and TGFB1 genes. For IL6, the A allele (OR=0.95, 95% CI 0.91–0.99) and AA genotype (OR=0.65, 95% CI 0.50–0.85) for the rs1800795 poly- morphism, and for sIL6R, the A allele (OR=0.96 95%, CI 0.92–1.00) and AA genotype (OR=0.72, 95% CI 0.55–0.94) the rs8192284 polymorphism were associated with signifcantly decreased schizophrenia risk. In the genotype-wise analysis for IL1B, homozygosity for either allele (AA: OR=1.91, 95% CI 1.60–2.27; and GG: OR=0.40, 95% CI 0.33–0.49) of the rs1143627 polymorphism was also signifcantly associated with schizophrenia risk. Conclusions: Associations between polymorphisms for the IL1B, IL6, and sIL6R genes and schizophrenia risk complement and extend previous fndings regarding immune dysfunction in this disorder, including genome-wide association studies. Future studies of cytokine expression in schizophrenia should consider the efect of these polymorphisms. Te fnding of potential “protective” alleles may also be relevant for at-risk populations. Original Contributions Meta-Analysis of Cytokine and Chemokine Genes in Schizophrenia Abstract Introduction Immunological abnormalities in schizophrenia have been one of the more enduring fndings in the feld, and a popular area of research over the last decade. Tis interest has been at least partially stimulated by our increased un- derstanding of the complex interactions that occur between the immune system and the brain in other chronic diseases. Polymorphisms in major histocompatibility complex genes, Key Words: Schizophrenia, Genetics, Single Nucleotide Polymorphisms, Cytokines, Meta-Analysis 1 Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 2 Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA Address for correspondence: Brian J. Miller, MD, PhD, MPH, Department of Psychiatry and Health Behavior, Augusta University, 997 Saint Sebastian Way, Augusta, GA 30912 Phone: +1-706-721-4445; Fax: +1-706-721-6602; E-mail: brmiller@augusta.edu Submitted: October 9, 2015; Revised: January 22, 2016; Accepted: March 15, 2016 Clinical Schizophrenia & Related Psychoses Fall 2018 • 121 Zachary D. Hudson 1 , Brian J. Miller 2 which are critical to immune function (1), as well as other immune system genes (2), are associated with increased risk of schizophrenia. Tere is evidence for abnormalities in immune cell numbers (3) and cytokine levels (4-6) in frst-episode psychosis, suggesting a role for immune dys- function that may be independent of antipsychotic medica- tions. Treatment with non-steroidal anti-infammatory drugs (NSAIDs), in adjunct to antipsychotics, has been associated with signifcant improvement in psychopathology in schizo- phrenia (7). Tese fndings provide important empirical sup- port for a pathophysiological role for infammation in some patients with schizophrenia. Aberrant blood levels of components of the cyto- kine network—including blood IL-1β, sIL-2R, IL-6, IL-12, interferon-gamma (IFN-γ), TNF-α, and transforming growth factor-beta (TGF-β) protein levels—have been reported in schizophrenia (4-6). Cytokines are key signaling molecules of the immune system that exert efects in the periphery and the brain. Tey are produced by both immune and non-