seeQTL: a searchable database for human eQTLs

Xia, Kai; Shabalin, Andrey A.; Huang, Shangyu; Madar, Vered; Zhou, Yi; Wang, Wei; Zou, Fei; Sun, Wei; Sullivan, Patrick F.; Wright, Fred A.

doi:10.1093/bioinformatics/btr678

Cited by 139 publications

(130 citation statements)

References 18 publications

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“…We then used the Ensembl Variant Effect Predictor web tool to annotate these variants for predicted functional consequences (http://www.ensembl.org/info/docs/tools/vep/index.html) and used Genevar 12, seeQTL (http://www.bios.unc.edu/research/genomic_software/seeQTL/) 13, and the University of Chicago eQTL browser (http://eqtl.uchicago.edu/cgi‐bin/gbrowse/eqtl/) to identify eQTLs.…”

Section: Methodsmentioning

confidence: 99%

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Merkel

Xie

Monach

et al. 2017

Arthritis & Rheumatology

143

154

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ObjectiveTo identify risk alleles relevant to the causal and biologic mechanisms of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).MethodsA genome‐wide association study and subsequent replication study were conducted in a total cohort of 1,986 cases of AAV (patients with granulomatosis with polyangiitis [Wegener's] [GPA] or microscopic polyangiitis [MPA]) and 4,723 healthy controls. Meta‐analysis of these data sets and functional annotation of identified risk loci were performed, and candidate disease variants with unknown functional effects were investigated for their impact on gene expression and/or protein function.ResultsAmong the genome‐wide significant associations identified, the largest effect on risk of AAV came from the single‐nucleotide polymorphism variants rs141530233 and rs1042169 at the HLA–DPB1 locus (odds ratio [OR] 2.99 and OR 2.82, respectively) which, together with a third variant, rs386699872, constitute a triallelic risk haplotype associated with reduced expression of the HLA–DPB1 gene and HLA–DP protein in B cells and monocytes and with increased frequency of complementary proteinase 3 (PR3)–reactive T cells relative to that in carriers of the protective haplotype. Significant associations were also observed at the SERPINA1 and PTPN22 loci, the peak signals arising from functionally relevant missense variants, and at PRTN3, in which the top‐scoring variant correlated with increased PRTN3 expression in neutrophils. Effects of individual loci on AAV risk differed between patients with GPA and those with MPA or between patients with PR3‐ANCAs and those with myeloperoxidase‐ANCAs, but the collective population attributable fraction for these variants was substantive, at 77%.ConclusionThis study reveals the association of susceptibility to GPA and MPA with functional gene variants that explain much of the genetic etiology of AAV, could influence and possibly be predictors of the clinical presentation, and appear to alter immune cell proteins and responses likely to be key factors in the pathogenesis of AAV.

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Section: Methodsmentioning

confidence: 99%

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Merkel

Xie

Monach

et al. 2017

Arthritis & Rheumatology

143

154

View full text Add to dashboard Cite

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“…For example, the amount of eQTL data available for the AA population (# eQTLs = 13,995) is only ~33.1% of that in the CEU population (# eQTLs = 42,301), which reduced the reliability of our observations in the AA data. Notably, the samples used for detection of eQTL in AA were comparable to those in CEU, indicating that AA samples tend to have fewer eQTLs regardless of sample size [33]. As for the JPT population, though the eQTL data is sufficient for our analysis, the sample size in the MEC-JPT GWAS dataset was only 392 (158 cases and 234 controls), which may not have sufficient power to detect PrCa-associated SNPs in the JPT population.…”

Section: Discussionmentioning

confidence: 99%

“…We utilized human eQTL association data from a recently developed public database, seeQTL [33], which collected 9 unrelated HapMap studies of lymphoblastoid cell lines [6, 7, 9-11, 34, 35], human cortical samples [5], and monocytes [36]. In the seeQTL database, eQTL data from these previous studies was collected and re-analyzed using a combination of quality control, population stratification, and false discovery rate (FDR) assessement to generate cis - and trans -eQTLs.…”

Section: Methodsmentioning

confidence: 99%

Top associated SNPs in prostate cancer are significantly enriched incis-expression quantitative trait loci and at transcription factor binding sites

et al. 2014

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While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory structure in prostate cancer is unclear.We investigated the potential regulatory roles of risk variants in two prostate cancer GWAS datasets by their interactions with expression quantitative trait loci (eQTL) and/or transcription factor binding sites (TFBSs) in three populations.Our results indicated that the moderately associated GWAS SNPs were significantly enriched with cis-eQTLs and TFBSs in Caucasians (CEU), but not in African Americans (AA) or Japanese (JPT); this was also observed in an independent pan-cancer related SNPs from the GWAS Catalog. We found that the eQTL enrichment in the CEU population was tissue-specific to eQTLs from CEU lymphoblastoid cell lines. Importantly, we pinpointed two SNPs, rs2861405 and rs4766642, by overlapping results from cis-eQTL and TFBS as applied to the CEU data.These results suggested that prostate cancer associated SNPs and pan-cancer associated SNPs are likely to play regulatory roles in CEU. However, the negative enrichment results in AA or JPT and the potential mechanisms remain to be elucidated in additional samples.

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“…To identify eQTL effects, eQTL databases were analyzed (Borel et al., 2011; Dimas et al., 2009; Dixon et al., 2007; Fehrmann et al., 2011; Greenawalt et al., 2011; Grundberg et al., 2009; GTEx Consortium, 2015; Kim, Cho, Lee, & Webster, 2012; Kirsten et al., 2015; Mehta et al., 2013; Myers et al., 2007; Ramasamy et al., 2014; Schadt et al., 2008; Schröder et al., 2011; Veyrieras et al., 2008; Westra et al., 2013; Xia et al., 2012; Zeller et al., 2010). We only considered SNPs identified in brain or blood tissue and eQTLs had to be replicated in at least one study.…”

Section: Methodsmentioning

confidence: 99%

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

et al. 2017

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BackgroundDyslexia is a specific learning disorder affecting reading and spelling abilities. Its prevalence is ~5% in German‐speaking individuals. Although the etiology of dyslexia largely remains to be determined, comprehensive evidence supports deficient phonological processing as a major contributing factor. An important prerequisite for phonological processing is auditory discrimination and, thus, essential for acquiring reading and spelling skills. The event‐related potential Mismatch Response (MMR) is an indicator for auditory discrimination capabilities with dyslexics showing an altered late component of MMR in response to auditory input.MethodsIn this study, we comprehensively analyzed associations of dyslexia‐specific late MMRs with genetic variants previously reported to be associated with dyslexia‐related phenotypes in multiple studies comprising 25 independent single‐nucleotide polymorphisms (SNPs) within 10 genes.ResultsFirst, we demonstrated validity of these SNPs for dyslexia in our sample by showing that additional inclusion of a polygenic risk score improved prediction of impaired writing compared with a model that used MMR alone. Secondly, a multifactorial regression analysis was conducted to uncover the subset of the 25 SNPs that is associated with the dyslexia‐specific late component of MMR. In total, four independent SNPs within DYX1C1 and ATP2C2 were found to be associated with MMR stronger than expected from multiple testing. To explore potential pathomechanisms, we annotated these variants with functional data including tissue‐specific expression analysis and eQTLs.ConclusionOur findings corroborate the late component of MMR as a potential endophenotype for dyslexia and support tripartite relationships between dyslexia‐related SNPs, the late component of MMR and dyslexia.

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seeQTL: a searchable database for human eQTLs

Cited by 139 publications

References 18 publications

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody–Associated Vasculitis

Top associated SNPs in prostate cancer are significantly enriched incis-expression quantitative trait loci and at transcription factor binding sites

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

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