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Affymetrix SNP array data for Japanese schizophrenia samples

ABSTRACT: Genome-wide association study (GWAS) was performed in 120 patient-parents trio samples from Japanese schizophrenia pedigrees ABSTRACT: Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p < 0.01 and 473 SNPs of p < 0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE27923 | GEO | 2011/06/13

SECONDARY ACCESSION(S): PRJNA137837

REPOSITORIES: GEO

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Project description:Genome-wide association study (GWAS) was performed in 120 patient-parents trio samples from Japanese schizophrenia pedigrees ABSTRACT: Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p < 0.01 and 473 SNPs of p < 0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. SUPPLEMENTARY FILES: CEL files were processed by manufacture's protocol. Genotype data were analyzed with the GeneSpring GT (Varia) 2.0 software package developed by Agilent Technologies (Santa Clara, CA). Matrix tables for the Genetic programs were produced (Linkage format: http://bioinformatics.med.utah.edu/~alun/software/docs/linkage.html) File 1: Matrix file_SNP_Map.txt File 2: Matrix file_Family_Information.txt File 3: Matrix file_Pedigree_Format.txt (Genotyping data of Linkage format) Transmission disequilibrium test was performed using the R program (http://www.r-project.org). File 4: Matrix file_results.txt

Project description:Despite of multiple systematic studies of schizophrenia pathogenesis, reconstruction of the mechanism established on proteomics, metabolomics, and genome-wide significant loci is still a challenging task. We suggested that advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) may enhance the current evidence and fundamental knowledge about molecular pathogenesis of schizophrenia. Liquide chromatography and ultra-high-resolution mass-spectrometry were utilized for proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. Proteomic and metabolomic results were quantitatively evaluated and overlayed on the GWAS data. After statistical analysis using R-package, the resulting features were associated in a multilayer mode with adjusted biological processes in a reconstructed unified map of molecular events. We have identified 20 DFE proteins that were validated on an independent cohort of patients that are significant for schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. Almost half of them are new for schizophrenia. The metabolomic survey revealed 18 compounds most of which were the part transformation of tyrosine and steroids with the incline to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.) which were extracted as group-specific determinants that permits to isolate patients with schizophrenia. The GWAS assay revealed 52 loci were integrated into proteome-metabolome data as significantly implicated in schizophrenia. We integrated three layers of omics science (proteomics, metabolomics and GWAS) and quantitative analysis utilized systematic approach to reconstruct the proposed map of molecular events associated with the considered psychopathology. The resulting interplay between different layers emphasized strict implication of lipids metabolism, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones and sex hormones interconnection. The proposed interplay map can give opportunity in the understanding how the regulation of distinct metabolic axis is achieved and what happens in proteome arrangements to produce a schizophrenia-specific pattern of pathology condition.

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Affymetrix SNP array data for Japanese schizophrenia samples

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