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dc.contributor.authorZhang, Ten_US
dc.contributor.authorChoi, Jen_US
dc.contributor.authorKovacs, MAen_US
dc.contributor.authorShi, Jen_US
dc.contributor.authorXu, Men_US
dc.contributor.authorNISC Comparative Sequencing Programen_US
dc.contributor.authorMelanoma Meta-Analysis Consortiumen_US
dc.contributor.authorGoldstein, AMen_US
dc.contributor.authorTrower, AJen_US
dc.contributor.authorBishop, DTen_US
dc.contributor.authorIles, MMen_US
dc.contributor.authorDuffy, DLen_US
dc.contributor.authorMacGregor, Sen_US
dc.contributor.authorAmundadottir, LTen_US
dc.contributor.authorLaw, MHen_US
dc.contributor.authorLoftus, SKen_US
dc.contributor.authorPavan, WJen_US
dc.contributor.authorBrown, KMen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-04T16:21:46Z
dc.date.issued2018-11en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30333196en_US
dc.identifiergr.233304.117en_US
dc.identifier.citationGenome Res, 2018, 28 (11), pp. 1621 - 1635en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3046
dc.identifier.eissn1549-5469en_US
dc.identifier.doi10.1101/gr.233304.117en_US
dc.description.abstractMost expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4 Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology.en_US
dc.format.extent1621 - 1635en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.subjectBasic Helix-Loop-Helix Transcription Factorsen_US
dc.subjectCarrier Proteinsen_US
dc.subjectCells, Cultureden_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHemeproteinsen_US
dc.subjectHumansen_US
dc.subjectInterferon Regulatory Factorsen_US
dc.subjectLinkage Disequilibriumen_US
dc.subjectMelanocytesen_US
dc.subjectMelanomaen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectQuantitative Trait Locien_US
dc.titleCell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-09-21en_US
rioxxterms.versionofrecord10.1101/gr.233304.117en_US
rioxxterms.licenseref.startdate2018-11en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfGenome Resen_US
pubs.issue11en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublisheden_US
pubs.volume28en_US
pubs.embargo.termsNot knownen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorSwerdlow, Anthonyen_US


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