Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Affymetrix SNP array data for esophageal squamous cell carcinoma (ESCC) samples

ABSTRACT: We demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual,suggesting an influence of genetic background on DNA methylation. Recent studies have shown a genetic influence on gene expression variation, chromatin, and DNA methylation. However, the effects of genetic background and tissue types on DNA methylation at the genome-wide level have not been characterized extensively. To study the effect of genetic background and tissue types on global DNA methylation, we performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNA from 30 patients with esophageal squamous cell carcinoma (ESCC). The use of multiple tissues from 30 individuals allowed us to evaluate variation of DNA methylation states across tissues and individuals. Our results demonstrate that blood and esophageal tissues shared similar DNA methylation patterns within the same individual, suggesting an influence of genetic background on DNA methylation. Furthermore, we showed that tissue types are important contributors of DNA methylation states. Methylation and gDNA intensity data derived from Affymetrix 500k array. 30 individuals with blood, normal and tumor esophageal tissues.

ORGANISM(S): Homo sapiens

SUBMITTER: Howard Yang

PROVIDER: E-GEOD-20123 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Influence of genetic background and tissue types on global DNA methylation patterns.

Yang Howard H HH Hu Nan N Wang Chaoyu C Ding Ti T Dunn Barbara K BK Goldstein Alisa M AM Taylor Philip R PR Lee Maxwell P MP

PloS one 20100223 2

Recent studies have shown a genetic influence on gene expression variation, chromatin, and DNA methylation. However, the effects of genetic background and tissue types on DNA methylation at the genome-wide level have not been characterized extensively. To study the effect of genetic background and tissue types on global DNA methylation, we performed DNA methylation analysis using the Affymetrix 500K SNP array on tumor, adjacent normal tissue, and blood DNA from 30 patients with esophageal squamo ...[more]

PMID: 20186319

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Project description:Background: The mechanisms of how genetic variants (SNPs) identified in genome-wide association studies act to influence body mass remain unknown for most of these SNPs, which continue to puzzle the scientific community. Recent evidence points to epigenetic and chromatin state of the genome to have an important role. Methods: 355 healthy young individuals were genotyped for 52 known obesity-associated SNPs and we obtained DNA methylation levels in their blood using the Illumina 450K BeadChip. Associations between alleles and methylation at proximal cytosine residues were tested using a linear model adjusted for age, sex, weight category and a proxy for blood cell type counts. For replication in other tissues, we used two open-access datasets (skin fibroblasts, n=62; four brain regions, n=121-133) and an additional dataset in subcutaneous and visceral fat (n=149). Results: We found that alleles at 28 of these obesity-associated SNPs associate with methylation levels at 107 proximal CpG sites. Out of 107 CpG sites, 38 are located in gene promoters, including genes strongly implicated in obesity (MIR148A, BDNF, PTPMT1, NR1H3, MGAT1, SCGB3A1, HOXC12, PMAIP1, PSIP1, RPS10-NUDT3, RPS10, SKOR1, MAP2K5, SIX5, AGRN, IMMP1L, ELP4, ITIH4, SEMA3G, POMC, ADCY3, SSPN, LGR4, TUFM, MIR4721, SULT1A1, SULT1A2, APOBR, CLN3, SPNS1,SH2B1, ATXN2L, and IL27). Interestingly, the associated SNPs are in known eQTLs for some of these genes. We also found that the 107 CpGs are enriched in enhancers in peripheral blood mononuclear cells. Finally, our results indicate that some of these associations are not be blood-specific as we successfully replicated four associations in skin fibroblasts. Conclusions: Our results strongly suggest that many obesity-associated SNPs are associated with proximal gene regulation, which was reflected by association of obesity risk allele genotypes with differential DNA methylation. This study highlights the importance of DNA methylation and other chromatin marks as a way to understand the molecular basis of genetic variants associated to human diseases and traits. Bisulphite converted DNA from 355 individuals aged 14-34 were hybridised to the Illumina Infinium 450k Human Methylation Beadchip.

Dataset Information

Affymetrix SNP array data for esophageal squamous cell carcinoma (ESCC) samples

Publications

Influence of genetic background and tissue types on global DNA methylation patterns.

Similar Datasets

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