Convergent Evidence Shows a Positive Association of Interleukin-1 Gene Complex Locus with Susceptibility to Schizophrenia in the Caucasian population

Recent genetic studies have revealed that the Interleukin-1 (IL1) gene complex (IL1 alpha, IL1 beta and IL1 receptor antagonist) is associated with schizophrenia, but contradictory findings have also been reported. We investigated the association of the IL1 gene complex locus and schizophrenia using meta-analytic techniques, covering all published data up to January 2010, to restrict to the most commonly reported 4 single nucleotide polymorphisms (SNP). We also explored potential sources of heterogeneity and to investigate whether ancestry and study design moderated any association. The combined allele-wise odds ratio (OR) for schizophrenia of the rs16944 (IL1B gene; T-511C) polymorphism was 0.86 (95% CI: 0.77to 0.96).When applying stratified analysis to this polymorphism, the pooled allele-wise OR was 0.88 (95% CI, 0.79 to 0.97) in 10 population-based studies and 0.85 (95% CI: 0.73 to 0.99) in Caucasian samples. In a stratified analysis of the rs1143634 (IL1B gene; T3953C) polymorphism, the pooled genotype-wise results in a dominant model were also statistically significant both in a population-based study subgroup with summary OR of 0.64 (95% CI: 0.41 to 0.99) and a Caucasian population subgroup with summary OR of 0.62 (95% CI: 0.40 to 0.97). Neither combined nor stratified analyses found any association of the rs1800587 (IL1A gene; T-889C) or rs1794068 (IL1RA Gene; IL1RN_86 bp; T/C) with schizophrenia susceptibility. Our study suggests the IL1B gene or the IL1 gene complex may play a moderate role in the etiology of schizophrenia in the Caucasian population.