{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:41:18Z","timestamp":1767109278728,"version":"3.37.3"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T00:00:00Z","timestamp":1542931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA118100"],"award-info":[{"award-number":["P30CA118100"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Expression quantitative trait loci (eQTLs) have been touted as the missing piece that can bridge the gap between genetic variants and phenotypes. Over the past decade, we have witnessed a sharp rise of effort in the identification and application of eQTLs. The successful application of eQTLs relies heavily on their reproducibility. The current eQTL databases such as Genotype-Tissue Expression (GTEx) were populated primarily with eQTLs deriving from germline single nucleotide polymorphisms and normal tissue gene expression. The novel scenarios that employ eQTL models for prediction purposes often involve disease phenotypes characterized by altered gene expressions. To evaluate eQTL reproducibility across diverse data sources and the effect of disease-specific gene expression alteration on eQTL identification, we conducted an eQTL study using 5178 samples from The Cancer Genome Atlas (TCGA). We found that the reproducibility of eQTLs between normal and tumor tissues was low in terms of the number of shared eQTLs. However, among the shared eQTLs, the effect directions were generally concordant. This suggests that the source of the gene expression (normal or tumor tissue) has a strong effect on the detectable eQTLs and the effect direction of the eQTLs. Additional analyses demonstrated good directional concordance of eQTLs between GTEx and TCGA. Furthermore, we found that multi-tissue eQTLs may exert opposite effects across multiple tissue types. In summary, our results suggest that eQTL prediction models need to carefully address tissue and disease dependency of eQTLs. Tissue\u2013disease-specific eQTL databases can afford more accurate prediction models for future studies.<\/jats:p>","DOI":"10.1093\/bib\/bby108","type":"journal-article","created":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T02:55:32Z","timestamp":1542423332000},"page":"338-347","source":"Crossref","is-referenced-by-count":6,"title":["Cancer-specific expression quantitative loci are affected by expression dysregulation"],"prefix":"10.1093","volume":"21","author":[{"given":"Quanhu","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center , Nashville, TN, USA"}]},{"given":"David C","family":"Samuels","sequence":"additional","affiliation":[{"name":"Vanderbilt Genetics Institute , Dept. of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN, USA"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of New Mexico , Albuquerque, NM, USA"}]},{"given":"Scott","family":"Ness","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of New Mexico , Albuquerque, NM, USA"}]},{"given":"Ying-yong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China , School of Life Sciences, Northwest University, Xi\u2019an, Shaanxi, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-3960","authenticated-orcid":false,"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of New Mexico , Albuquerque, NM, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,11,23]]},"reference":[{"key":"2023060106354126300_ref1","first-page":"175","article-title":"Mining microarray data at NCBI's Gene Expression Omnibus (GEO)*","volume":"338","author":"Barrett","year":"2006","journal-title":"Methods Mol Biol"},{"key":"2023060106354126300_ref2","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1073\/pnas.0903103106","article-title":"Potential etiologic and functional implications of genome-wide association loci for human diseases and traits","volume":"106","author":"Hindorff","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023060106354126300_ref3","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ng.840","article-title":"Principles for the post-GWAS functional characterization of cancer risk loci","volume":"43","author":"Freedman","year":"2011","journal-title":"Nat Genet"},{"key":"2023060106354126300_ref4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1186\/s13059-014-0469-0","article-title":"Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes","volume":"15","author":"Blattler","year":"2014","journal-title":"Genome Biol"},{"key":"2023060106354126300_ref5","doi-asserted-by":"crossref","first-page":"8641","DOI":"10.1093\/nar\/gkw519","article-title":"Explaining the disease phenotype of intergenic SNP through predicted long range regulation","volume":"44","author":"Chen","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"2023060106354126300_ref6","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat Genet"},{"key":"2023060106354126300_ref7","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1038\/ng.3367","article-title":"A gene-based association method for mapping traits using reference transcriptome data","volume":"47","author":"Gamazon","year":"2015","journal-title":"Nat Genet"},{"article-title":"Quality and concordance of genotyping array data of 12,064 samples from 5840 cancer patients","year":"2018","author":"Guo","key":"2023060106354126300_ref8"},{"key":"2023060106354126300_ref9","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat Biotechnol"},{"key":"2023060106354126300_ref10","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/bioinformatics\/bts163","article-title":"Matrix eQTL: ultra fast eQTL analysis via large matrix operations","volume":"28","author":"Shabalin","year":"2012","journal-title":"Bioinformatics"},{"key":"2023060106354126300_ref11","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1073\/pnas.94.3.952","article-title":"Expression genetics in cancer: shifting the focus from DNA to RNA","volume":"94","author":"Sager","year":"1997","journal-title":"Proc Natl Acad Sci USA"},{"issue":"Suppl 6","key":"2023060106354126300_ref12","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1186\/s12864-017-4022-x","article-title":"The discrepancy among single nucleotide variants detected by DNA and RNA high throughput sequencing data","volume":"18","author":"Guo","year":"2017","journal-title":"BMC Genomics"},{"key":"2023060106354126300_ref13","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1126\/science.1069516","article-title":"Genetic dissection of transcriptional regulation in budding yeast","volume":"296","author":"Brem","year":"2002","journal-title":"Science"},{"key":"2023060106354126300_ref14","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.cell.2012.12.034","article-title":"Integrative eQTL-based analyses reveal the biology of breast cancer risk loci","volume":"152","author":"Li","year":"2013","journal-title":"Cell"},{"key":"2023060106354126300_ref15","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nrg1964","article-title":"Genetics of global gene expression","volume":"7","author":"Rockman","year":"2006","journal-title":"Nat Rev Genet"},{"key":"2023060106354126300_ref16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nrg.2017.22","article-title":"Disease genomics: transitioning from association to causation with eQTLs","volume":"18","author":"Clyde","year":"2017","journal-title":"Nat Rev Genet"},{"key":"2023060106354126300_ref17","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrg3891","article-title":"The role of regulatory variation in complex traits and disease","volume":"16","author":"Albert","year":"2015","journal-title":"Nat Rev Genet"},{"key":"2023060106354126300_ref18","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1126\/science.1262110","article-title":"Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans","volume":"348","author":"GTEx Consortium","year":"2015","journal-title":"Science"},{"key":"2023060106354126300_ref19","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bav025","article-title":"SCAN database: facilitating integrative analyses of cytosine modification and expression QTL","volume":"2015","author":"Zhang","year":"2015","journal-title":"Database (Oxford)"},{"key":"2023060106354126300_ref20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1093\/bioinformatics\/btr678","article-title":"seeQTL: a searchable database for human eQTLs","volume":"28","author":"Xia","year":"2012","journal-title":"Bioinformatics"},{"key":"2023060106354126300_ref21","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1101\/gr.142521.112","article-title":"A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines","volume":"23","author":"Liang","year":"2013","journal-title":"Genome Res"},{"key":"2023060106354126300_ref22","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1089\/omi.2016.0063","article-title":"Consensus genome-wide expression quantitative trait loci and their relationship with human complex trait disease","volume":"20","author":"Yu","year":"2016","journal-title":"OMICS"},{"key":"2023060106354126300_ref23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature13602","article-title":"Putative cis-regulatory drivers in colorectal cancer","volume":"512","author":"Ongen","year":"2014","journal-title":"Nature"},{"key":"2023060106354126300_ref24","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ajhg.2017.02.004","article-title":"Large-scale trans-eQTLs affect hundreds of transcripts and mediate patterns of transcriptional co-regulation","volume":"100","author":"Brynedal","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2023060106354126300_ref25","doi-asserted-by":"crossref","first-page":"e1004461","DOI":"10.1371\/journal.pgen.1004461","article-title":"Cis and trans effects of human genomic variants on gene expression","volume":"10","author":"Bryois","year":"2014","journal-title":"PLoS Genet"},{"key":"2023060106354126300_ref26","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ajhg.2017.05.002","article-title":"Dynamic role of trans regulation of gene expression in relation to complex traits","volume":"100","author":"Yao","year":"2017","journal-title":"Am J Hum Genet"},{"key":"2023060106354126300_ref27","doi-asserted-by":"crossref","first-page":"e1002639","DOI":"10.1371\/journal.pgen.1002639","article-title":"Patterns of cis regulatory variation in diverse human populations","volume":"8","author":"Stranger","year":"2012","journal-title":"PLoS Genet"},{"key":"2023060106354126300_ref28","doi-asserted-by":"crossref","first-page":"e00523","DOI":"10.7554\/eLife.00523","article-title":"Passive and active DNA methylation and the interplay with genetic variation in gene regulation","volume":"2","author":"Gutierrez-Arcelus","year":"2013","journal-title":"Elife"},{"key":"2023060106354126300_ref29","doi-asserted-by":"crossref","first-page":"R10","DOI":"10.1186\/gb-2011-12-1-r10","article-title":"DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines","volume":"12","author":"Bell","year":"2011","journal-title":"Genome Biol"},{"key":"2023060106354126300_ref30","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ng.3721","article-title":"Disease variants alter transcription factor levels and methylation of their binding sites","volume":"49","author":"Bonder","year":"2017","journal-title":"Nat Genet"},{"key":"2023060106354126300_ref31","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1186\/gb-2014-15-2-r37","article-title":"The relationship between DNA methylation, genetic and expression inter-individual variation in untransformed human fibroblasts","volume":"15","author":"Wagner","year":"2014","journal-title":"Genome Biol"},{"key":"2023060106354126300_ref32","doi-asserted-by":"crossref","first-page":"e105393","DOI":"10.1371\/journal.pone.0105393","article-title":"Systematic genetic analysis identifies Cis-eQTL target genes associated with glioblastoma patient survival","volume":"9","author":"Chen","year":"2014","journal-title":"PLoS One"},{"key":"2023060106354126300_ref33","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng.3523","article-title":"Gene regulatory mechanisms underpinning prostate cancer susceptibility","volume":"48","author":"Whitington","year":"2016","journal-title":"Nat Genet"},{"key":"2023060106354126300_ref34","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1002\/ijc.30205","article-title":"Role of ATG10 expression quantitative trait loci in non-small cell lung cancer survival","volume":"139","author":"Xie","year":"2016","journal-title":"Int J Cancer"},{"key":"2023060106354126300_ref35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/s12864-017-3750-2","article-title":"In silico pathway analysis and tissue specific cis-eQTL for colorectal cancer GWAS risk variants","volume":"18","author":"Loo","year":"2017","journal-title":"BMC Genomics"},{"key":"2023060106354126300_ref36","doi-asserted-by":"crossref","first-page":"D971","DOI":"10.1093\/nar\/gkx861","article-title":"PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer types","volume":"46","author":"Gong","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2023060106354126300_ref37","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-60327-411-1_1","article-title":"SNPs: impact on gene function and phenotype","volume":"578","author":"Shastry","year":"2009","journal-title":"Methods Mol Biol"}],"container-title":["Briefings in Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/21\/1\/338\/50498353\/bby108.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bib\/article-pdf\/21\/1\/338\/50498353\/bby108.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T06:42:39Z","timestamp":1685601759000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bib\/article\/21\/1\/338\/5194058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,23]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1,17]]}},"URL":"https:\/\/doi.org\/10.1093\/bib\/bby108","relation":{},"ISSN":["1467-5463","1477-4054"],"issn-type":[{"type":"print","value":"1467-5463"},{"type":"electronic","value":"1477-4054"}],"subject":[],"published-other":{"date-parts":[[2020,1]]},"published":{"date-parts":[[2018,11,23]]}}}