Association analysis of putative cis-acting polymorphisms of interleukin-19 gene with schizophrenia

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 50; pp. 151 - 156
• Main Authors: Okazaki, Satoshi, Watanabe, Yuichiro, Hishimoto, Akitoyo, Sasada, Toru, Mouri, Kentaro, Shiroiwa, Kyoichi, Eguchi, Noriomi, Ratta-Apha, Woraphat, Otsuka, Ikuo, Nunokawa, Ayako, Kaneko, Naoshi, Shibuya, Masako, Someya, Toshiyuki, Shirakawa, Osamu, Sora, Ichiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 03.04.2014; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Asian Continental Ancestry Group - genetics; Asian Continental Ancestry Group - psychology; Biological and medical sciences; Case-Control Studies; eQTL; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Genotype; Haplotype; Haplotypes; Humans; IL-19; Interleukins - genetics; Male; Medical sciences; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Polymorphism, Single Nucleotide - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Quantitative Trait Loci - genetics; Schizophrenia; Schizophrenia - genetics; SNP; GWAS; SNP; IL-19; HWE; LD; Schizophrenia; eQTL; Haplotype; Psychosis; Gene; Interleukin; Cytokine; Genetics; Polymorphism
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2013.12.006

Genome-wide association studies (GWAS) and gene expression analyses have revealed that single nucleotide polymorphisms (SNPs) associated with multifactorial diseases, such as schizophrenia, are significantly more likely to be associated with expression quantitative trait loci (eQTL). It was recently suggested that an immune system imbalance plays an important role in the pathogenesis of schizophrenia. Interleukin-19 is a novel cytokine that may play multiple roles in immune regulation and various diseases. We selected eight tag SNPs in the eQTL of the IL-19 gene. Seven of the SNPs are putative cis-acting SNPs. Then, we conducted a case–control study using two independent samples. The first sample comprised 567 schizophrenia patients and 710 controls, and the second sample comprised 677 schizophrenia patients and 667 controls. We identified the TGAA haplotype as being significantly associated with schizophrenia (p=0.0036 and corrected p=0.0264), although a combined analysis of the TGAA haplotype with the replication samples exhibited a nominally significant difference (p=0.022 and corrected p=0.235). These results suggest that the IL-19 gene might slightly contribute to the genetic risk of schizophrenia. Thus, further research on the association of eQTL SNPs with schizophrenia is warranted. •Cytokines are involved in the pathology of schizophrenia.•The putative cis-acting haplotype of the IL-19 gene is associated with schizophrenia.•IL-19 might contribute to the genetic risk of schizophrenia.