Replication of Association between Schizophrenia and Chromosome 6p21-6p22.1 Polymorphisms in Chinese Han PopulationReport as inadecuate




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Chromosome 6p21-p22.1, spanning the extended major histocompatibility complex MHC region, is a highly polymorphic, gene-dense region. It has been identified as a susceptibility locus of schizophrenia in Europeans, Japanese, and Chinese. In our previous two-stage genome-wide association study GWAS, polymorphisms of zinc finger with KRAB and SCAN domains 4 ZKSCAN4, nuclear factor-κB-activating protein-like NKAPL, and piggyBac transposable element derived 1 PGBD1, localized to chromosome 6p21-p22.1, were strongly associated with schizophrenia. To further investigate the association between polymorphisms at this locus and schizophrenia in the Chinese Han population, we selected eight other single-nucleotide polymorphisms SNPs distributed in or near these genes for a case-control association study in an independent sample of 902 cases and 1,091 healthy controls in an attempt to replicate the GWAS results. Four of these eight SNPs rs12214383, rs1150724, rs3800324, and rs1997660 displayed a nominal difference in allele frequencies between the case and control groups. The association between two of these SNPs and schizophrenia were significant even after Bonferroni correction rs12000: allele A>G, P = 2.50E-04, odds ratio OR = 1.27, 95% confidence interval CI = 1.12–1.45; rs1150722: allele C>T, P = 4.28E-05, OR = 0.55, 95% CI = 0.41–0.73. Haplotype ATTGACGC, comprising these eight SNPs rs2235359, rs2185955, rs12214383, rs12000, rs1150724, rs1150722, rs3800324, and rs1997660, was significantly associated with schizophrenia P = 6.60E-05. We also performed a combined study of this replication sample and the first-stage GWAS sample. The combined study revealed that rs12000 and rs1150722 were still strongly associated with schizophrenia rs12000: allele G>A, Pcombined = 0.0019, OR = 0.81; rs1150722: allele G>A, Pcombined = 3.00E-04, OR = 0.61. These results support our findings that locus 6p21-p22.1 is significantly associated with schizophrenia in the Chinese Han population and encourage further studies of the functions of these genetic factors.



Author: Yang Zhang, Tianlan Lu, Hao Yan, Yanyan Ruan, Lifang Wang, Dai Zhang, Weihua Yue , Lin Lu

Source: http://plos.srce.hr/



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