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Introduction Previous reports have found that polymorphisms in the close homologue of L1 ( CHL1) gene located on chromosome 3p26 are associated with schizophrenia among different ethnic populations. The aim of this study was to examine the associations of single nucleotides polymorphisms ( SNPs) of the CHL1 gene locus, including rs2055314 ( C/T), rs2272522 ( C/T) and rs331894 ( A/G), with schizophrenia in the Qatari population. Methods An association case control study was carried out on 86 Qatari schizophrenic patients from the Psychiatry Hospital, Hammed Medical Corporation, Qatar and 88 Qatari unrelated, healthy, control subjects. Schizophrenia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition ( DSM-IV) criteria for schizophrenia by two independent psychiatrists. Genotyping of the SNPs rs2055314 ( C/T), rs2272522 ( C/T) and rs331894 ( A/G) was conducted using the 5′ nuclease assay with the TaqMan MGB probe and an ABI 7500. Results Individuals with the rs2272522 TT genotype had approximately 4.2 times greater risk of schizophrenia compared to individuals with the CC genotype ( OR = 4.21; 95% CI: 1.12-15.53; P = 0.047). In addition, individuals carrying a T allele of the rs2272522 SNP had a significantly increased risk of schizophrenia (1.78 times) among the population ( P = 0.028). SNPs rs2055314 and rs331894 had no significant association with schizophrenia. Pairwise linkage disequilibrium ( LD) between the three polymorphisms was modest in the schizophrenic group. Discussion The rs2272522 polymorphism was found to exhibit a highly significant association with schizophrenia in the Qatari population. This finding supports the hypothesis that cell adhesion molecules may be involved in the etiology of this disease among Qatari patients. [ABSTRACT FROM AUTHOR]