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Association analysis of CHRNA3 polymorphisms with schizophrenia in a Chinese Han population: A case-control study.

ABSTRACT: Schizophrenia (SCZ) is a highly heritable, chronic, severe psychiatric disorder associated with significant financial costs to families and societies. In this case-control study, we investigated the associations between seven SNPs in CHRNA3 gene and the risk of SCZ.A total of 1071 (384 cases and 687 controls) unrelated subjects were recruited for our association study. Seven candidate tagging SNPs in CHRNA3 gene (rs3743077, rs1317286, rs938682, rs12914385, rs2869546, rs3743075, rs8040868) selected in HapMap database were genotyped by Sequenom MassARRAY. Finally, association analysis was conducted under various models.According to our results, in genetic model analysis, rs12914385 and rs8040868 are associated with decreased risk of SCZ in female subgroup; rs3743075 is associated with decreased risk of SCZ in subgroup with age?<45; while rs3743077 and rs2869546 are associated with increased risk of SCZ. Haplotype analysis suggested that the 3 variants comprised 1 block, and that the haplotype Ars938682Crs12914385Crs2869546 was significantly correlated with an increased risk of SCZ in the subgroup with age ?45.Our data indicate potential associations between CHRNA3polymorphisms and SCZ susceptibility, and the significant variants identified in our study may be used as genetic biomarkers for SCZ susceptibility in Chinese Han population.

SUBMITTER: Li G

PROVIDER: S-EPMC5999463 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Association analysis of CHRNA3 polymorphisms with schizophrenia in a Chinese Han population: A case-control study.

Li Guixin G Bai Mei M Guo Chenghao C Zhu Linhao L Wang Li L Yuan Dongya D Jin Tianbo T He Yongjun Y

Medicine 20180601 23

Schizophrenia (SCZ) is a highly heritable, chronic, severe psychiatric disorder associated with significant financial costs to families and societies. In this case-control study, we investigated the associations between seven SNPs in CHRNA3 gene and the risk of SCZ.A total of 1071 (384 cases and 687 controls) unrelated subjects were recruited for our association study. Seven candidate tagging SNPs in CHRNA3 gene (rs3743077, rs1317286, rs938682, rs12914385, rs2869546, rs3743075, rs8040868) select ...[more]

PMID: 29879020

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Project description:BackgroundThe expression of μ-opioid receptor has important role in cognitive dysfunction in Schizophrenia (SZ). The results of studies about the association of polymorphisms of μ-opioid receptor gene (OPRM1) with SZ were inconsistent.MethodsWe conducted a case-control study to investigate the genetic association between OPRM1 polymorphisms and SZ among the Han chinese population. 264 SZ patients and 264 age-matched control subjects were recruited. Four SNPs of OPRM1 were successfully genotyped by using PCR-RFLP.ResultsOf four polymorphisms, rs1799971 and rs2075572 were shown to associate with SZ. Compared with the A allele of rs1799971 and C allele of rs2075572, the G allele of rs1799971 and rs2075572 was associated with an almost 0.46-fold risk (OR=0.46, 95% CI: 0.357-0.59, P<0.01) and 0.7-fold risk (OR=0.707, 95% CI: 0.534-0.937, P=0.015) of the occurrence of SZ,. When subjects were divided by gender, rs1799971 remained significant difference only in males (OR=0.309, 95% CI: 0.218-0.439 for G allele, P<0.01), and rs2075572 only in females (OR=0.399, 95% CI: 0.246-0.648 for G allele, P<0.01). In secondary analysis with subsets of patients, the G allele of rs1799971 (compared to the A allele) was associated with a decreased risk of all patients and male patients with apathy symptoms (OR=0.086, 95% CI: 0.048-0.151, P=0.01; OR=0.083, 95% CI: 0.045-0.153, P<0.01), and the G allele of rs2075572 (compared to the C allele) was associated with a decreased risk of all patients and female patients with positive family history (OR=0.468, 95% CI: 0.309-0.71, P<0.01; OR=0.34, 95% CI: 0.195-0.593, P<0.01). In addition, haplotype analysis revealed that two SNP haplotypes (A-C-C-G and G-C-C-A) were associated with decreased risks of SZ (P<0.01). The other two (G-C-C-G and G-G-C-G) with increased risks of SZ (P<0.01).ConclusionsThe present study demonstrated for the first time that the OPRM1 polymorphism may be a risk factor for schizophrenia in the Han Chinese. Further studies are needed to give a global view of this polymorphism in pathogenesis of schizophrenia in a large-scale sample, family-based association design or well-defined subgroups of schizophrenia.

Project description: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-?B-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, P(combined) = 0.0019, OR = 0.81; rs1150722: allele G>A, P(combined) = 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.

Dataset Information

Association analysis of CHRNA3 polymorphisms with schizophrenia in a Chinese Han population: A case-control study.

Publications

Association analysis of CHRNA3 polymorphisms with schizophrenia in a Chinese Han population: A case-control study.

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