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

Zhang, Yang; Lu, Tianlan; Yan, Hao; Ruan, Yanyan; Wang, Lifang; Zhang, Dai; Yue, Weihua; Lu, Lin
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Chromosomal Mapping and Candidate Gene Discovery of Chicken Developmental Mutants and Genome-Wide Variation Analysis of MHC Congenics. ROBB, ELIZABETH A.; GITTER, CYNTHIA L.; CHENG, HANS H.; DELANY, MARY E. // Journal of Heredity;Mar2011, Vol. 102 Issue 2, p141 

    The chicken has been widely used in experimental research given its importance to agriculture and its utility as a model for vertebrate biology and biomedical pursuits for over 100 years. Herein we used advanced technologies to investigate the genomic characteristics of specialized chicken...

  • A comparison of major histocompatibility complex SNPs in Han Chinese residing in Taiwan and Caucasians. Hsin-Chou Yang; Chien-Hsin Lin; Chia-Ling Hsu; Shuen-Iu Hung; Jer-Yuan Wu; Wen-Harn Pan; Yuan-Tsong Chen; Fann, Cathy S. J. // Journal of Biomedical Science;Jul2006, Vol. 13 Issue 4, p489 

    Genetic dissection of complex diseases is both important and challenging. The human major histocompatibility complex is involved in many human diseases and genetic mechanisms. This highly polymorphic chromosome region has been extensively studied in Caucasians but not as well in Asians. Thus, we...

  • Identification of novel Tapasin polymorphisms and linkage disequilibrium to MHC class I alleles. Williams, Anthony P.; Bevan, Steven; Bunce, Mike; Houlston, Richard; Welsh, Kenneth I.; Elliott, Tim // Immunogenetics;Nov2000, Vol. 52 Issue 1/2, p9 

    Tapasin is a Mr 48,000 glycoprotein and has a specialized role in MHC class I-restricted antigen presentation. It is encoded by a gene which maps centromeric to the MHC class II region of human Chromosome 6 within 200 kb of HLA-DP. There is variable dependence upon tapasin for MHC class I...

  • HLA-Cw 0602 Associates More Strongly to Psoriasis in the Swedish Population than Variants of the Novel 6p21.3 Gene PSORS1C3. Holm, Sofia; Sánchez, Fabio; Carlén, Lina; Mallbris, Lotus; Ståhle, Mona; O'Brien, Kevin // Acta Dermato-Venereologica;Jan2005, Vol. 85 Issue 1, p2 

    The PSORS1 locus in the major histocompatibility complex region on chromosome 6p21.3 contains a major predisposing factor for psoriasis for which several candidate genes have been tested. The analyses are complicated by strong linkage disequilibrium in the region and the complex genetic...

  • A genetic association study in the Gambia using tagging polymorphisms in the major histocompatibility complex class III region implicates a HLA-B associated transcript 2 polymorphism in severe malaria susceptibility. Diakite, Mahamadou; Clark, Taane G.; Auburn, Sarah; Campino, Susana; Fry, Andrew E.; Green, Angela; Morris, Andrew P.; Richardson, Anna; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Kwiatkowski, Dominic P.; Rockett, Kirk A. // Human Genetics;Feb2009, Vol. 125 Issue 1, p105 

    The tumour necrosis factor (TNF) gene and other genes flanking it in the major histocompatibility complex (MHC) class III region are potentially important mediators of both immunity and pathogenesis of malaria. We investigated the association of severe malaria with 11 haplotype...

  • Multiple Sclerosis: Light at the end of the tunnel. Sawcer, Stephen; Compston, Alastair // European Journal of Human Genetics;Mar2006, Vol. 14 Issue 3, p257 

    The article highlights the two papers published in the March 2006 issue of the "European Journal of Human Genetics," which searched for genes that influence susceptibility to multiple sclerosis. The first paper identified 1068 single nucleotide polymorphisms from a 13.3 Mb interval including the...

  • Pathway-based analysis of genetic susceptibility to cervical cancer in situ: HLA-DPB1 affects risk in Swedish women. Ivansson, E L; Juko-Pecirep, I; Erlich, H A; Gyllensten, U B // Genes & Immunity;Dec2011, Vol. 12 Issue 8, p605 

    We have conducted a pathway-based analysis of genome-wide single-nucleotide polymorphism (SNP) data in order to identify genetic susceptibility factors for cervical cancer in situ. Genotypes derived from Affymetrix 500k or 5.0 arrays for 1076 cases and 1426 controls were analyzed for...

  • A sequence variation in the MOG gene is involved in multiple sclerosis susceptibility in Italy. D'Alfonso, S.; Bolognesi, E.; Guerini, F. R.; Barizzone, N.; Bocca, S.; Ferrante, D.; Castelli, L.; Bergamaschi, L.; Agliardi, C.; Ferrante, P.; Naldi, P.; Leone, M.; Caputo, D.; Ballerini, C.; Salvetti, M.; Galimberti, D.; Massacesi, L.; Trojano, M.; Momigliano-Richiardi, P. // Genes & Immunity;Jan2008, Vol. 9 Issue 1, p7 

    Several studies suggest that the histocompatibility complex (HLA) class I region harbours genes modulating multiple sclerosis (MS) susceptibility independently from the effect of class II alleles. A candidate gene in this region is MOG, encoding the myelin oligodendrocyte glycoprotein. A...

  • A polymorphism in human CD1A is associated with susceptibility to tuberculosis. Seshadri, C; Thuong, N T T; Yen, N T B; Bang, N D; Chau, T T H; Thwaites, G E; Dunstan, S J; Hawn, T R // Genes & Immunity;Apr/May2014, Vol. 15 Issue 3, p195 

    CD1 proteins are antigen-presenting molecules that evolved to present lipids rather than peptides to T cells. However, unlike major histocompatibility complex genes, CD1 genes show low rates of polymorphism and have not been clearly associated with human disease. We report that an intronic...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics