Mapping of Hepatic Expression Quantitative Trait Loci (eQTLs) in a Han Chinese Population
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE53792 | GEO | 2015/01/02
SECONDARY ACCESSION(S): PRJNA232969
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-02 | E-GEOD-53792 | biostudies-arrayexpress
Project description:BackgroundElucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world.MethodsWe performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population.ResultsOur analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10⁻⁸). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10⁻⁴). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both).ConclusionsOur study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.
| S-EPMC3995251 | biostudies-literature
Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64).
2015-01-02 | GSE53791 | GEO
Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64).
2015-01-02 | GSE53790 | GEO
Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64). Normal (non-diseased) liver tissues were previously collected from 64 Chinese donors who provided informed consent. All samples were stored frozen at -80M-bM-^DM-^C from collection until processing for RNA and DNA extraction. DNA /Total RNA of the human liver tissue samples were extracted by using the RNA/DNA Mini Kit (Qiagen, Hilden, Germany).each RNA sample were labeled and hybridized to the One-Color Agilent 60-mer Whole Human Genome Microarray (G4112F, GPL4133) at the Agilent Microarray Facility of Shanghai genomePilot Technology, Inc. The genome-wide scan was performed using the Affymetrix Genome-Wide Human SNP Array 6.0. We tested all expression traits for their associations with each of the QC passed SNPs using PLINK's assoc function for quantitative traits, which correlates allele dosage with changes in the trait.
2015-01-02 | E-GEOD-53791 | biostudies-arrayexpress
Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64). Normal (non-diseased) liver tissues were previously collected from 64 Chinese donors who provided informed consent. All samples were stored frozen at -80℃ from collection until processing for RNA and DNA extraction. DNA /Total RNA of the human liver tissue samples were extracted by using the RNA/DNA Mini Kit (Qiagen, Hilden, Germany).each RNA sample were labeled and hybridized to the One-Color Agilent 60-mer Whole Human Genome Microarray (G4112F, GPL4133) at the Agilent Microarray Facility of Shanghai genomePilot Technology, Inc. The genome-wide scan was performed using the Affymetrix Genome-Wide Human SNP Array 6.0. We tested all expression traits for their associations with each of the QC passed SNPs using PLINK's assoc function for quantitative traits, which correlates allele dosage with changes in the trait.
2015-01-02 | E-GEOD-53790 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-05-21 | E-GEOD-55232 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2014-05-21 | GSE55232 | GEO
Project description:Genome-wide association studies in European individuals have revealed that IL12A is strongly associated with primary biliary cirrhosis (PBC). However, this association was not detected in replicative studies conducted in Chinese Han and Japanese populations.To verify contributions of genetic variants of IL12A to the pathogenesis of PBC in Chinese populations, a replicative study of 22 single nucleotide polymorphisms (SNPs) around the IL12A gene locus was performed in a cohort of 586 PBC cases and 726 healthy controls. Three out of the 22 SNPs were significantly associated with PBC. The 2 SNPs with the most significant association signal were rs4679868 (P = 6.59E-05, odds ratio [OR] = 1.554 [1.253-1.927]) and rs6441286 (P = 8.00E-05, OR = 1.551 [1.250-1.924]). These 2 SNPs were strongly linked to each other (r = 0.981), and both were found to be significantly associated with PBC in European populations.An expression quantitative trait loci (eQTL) analysis was performed based on the observation that these 2 SNPs were located in proximity to 2 enhancers verified by luciferase reporter systems in the HEK293 cell line. The results of eQTL analysis, conducted using the publically accessible data, showed that the risk alleles of rs4679868 and rs6441286 were significantly associated with decreased expression of IL12A in lymphoblastoid cell lines derived from individuals of Chinese Han ancestry (P = 0.0031 for rs4679868 and P = 0.0073 for rs6441286). In addition, the risk alleles of the 2 SNPs were significantly associated with down-regulation of SCHIP1, a celiac disease susceptible gene, 91.5 kb upstream of IL12A.These results not only demonstrated that IL12A is associated with PBC in the Chinese Han population but also identified a potential mechanism for its involvement in the pathogenesis of PBC.
| S-EPMC4902537 | biostudies-literature
Project description:In recent years genome-wide association studies (GWAS) have uncovered numerous chromosomal loci associated with various electrocardiographic traits and cardiac arrhythmia predisposition. A considerable fraction of these loci lie within inter-genic regions. The underlying trait-associated variants likely reside in regulatory regions and exert their effect by modulating gene expression. Hence, the key to unraveling the molecular mechanisms underlying these cardiac traits is to interrogate variants for association with differential transcript abundance by expression quantitative trait locus (eQTL) analysis. In this study we conducted an eQTL analysis of human heart. For a total of 129 left ventricular samples that were collected from non-diseased human donor hearts, genome-wide transcript abundance and genotyping was determined using microarrays. Each of the 18,402 transcripts and 897,683 SNP genotypes that remained after pre-processing and stringent quality control were tested for eQTL effects. We identified 771 eQTLs, regulating 429 unique transcripts. Overlaying these eQTLs with cardiac GWAS loci identified novel candidates for studies aimed at elucidating the functional and transcriptional impact of these loci. Thus, this work provides for the first time a comprehensive eQTL map of human heart: a powerful and unique resource that enables systems genetics approaches for the study of cardiac traits.
| S-EPMC4028258 | biostudies-literature