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| 1 | | Nat. Genet. 2011 Dec 43: 1228-31 |
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| PMID | 22037552 |
| Title | Genome-wide association study identifies a susceptibility locus for schizophrenia in Han Chinese at 11p11.2. |
| Abstract | To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia. |
| SCZ Keywords | schizophrenia |
| 2 | | PLoS ONE 2013 -1 8: e56732 |
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| PMID | 23437227 |
| Title | Replication of association between schizophrenia and chromosome 6p21-6p22.1 polymorphisms in Chinese Han population. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia |
| 3 | | Schizophr. Res. 2015 Mar 162: 124-37 |
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| PMID | 25667193 |
| Title | Association between variants of zinc finger genes and psychiatric disorders: systematic review and meta-analysis. |
| Abstract | Psychiatric disorders have a negative impact on society and human lives. Genetic factors are involved in the occurrence and development of psychiatric diseases. ZNF804A has been identified as one of the most compelling risk genes associated with broad phenotypes related to psychosis. We conducted a systematic meta-analysis and reviewed ZNF804A variants in psychosis-related disorders, including schizophrenia, bipolar disorder, and attention-deficit hyperactivity disorder. We also summarized the association between other zinc finger protein genes (ZNFs) and psychiatric diseases. The meta-analysis included a total of six variants of ZNF804A and three variants of other ZNFs (ZDHHC8 and ZKSCAN4), and the effects of ZNF variants on neurocognition and neuroimaging phenotypes were reviewed. The biological functions of these variants are also presented. We verified that ZNF804A was significantly related to psychiatric diseases, and the association between ZNF804A rs1344706 and psychosis (schizophrenia and bipolar disorder) did not vary with disease or ethnicity. The main brain area regulated by ZNF804A rs1344706 was the dorsolateral prefrontal cortex. The effect of ZNF804A variants on cognition did not display consistency with different diseases or methodologies. These findings suggest that ZNF804A might play an important role in common pathogenesis of psychiatric diseases, and its variants are likely involved in regulating the expression of psychosis-related genes, especially the dopamine pathway genes. Further research should focus on the molecular mechanisms by which ZNF804A variants act in psychiatric diseases and related phenotypes. |
| SCZ Keywords | schizophrenia |
