Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci

Persistent Link:
http://hdl.handle.net/10150/610285
Title:
Enrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait loci
Author:
Hulur, Imge; Gamazon, Eric R.; Skol, Andrew D.; Xicola, Rosa M.; Llor, Xavier; Onel, Kenan; Ellis, Nathan A.; Kupfer, Sonia S.
Affiliation:
Committee on Genetics, Genomics and Systems Biology, University of Chicago; Department of Medicine, University of Chicago; Department of Pediatrics, University of Chicago; Department of Medicine, Yale University; University of Arizona Cancer Center; Division of Genetic Medicine, Department of Medicine, Vanderbilt University
Issue Date:
2015
Publisher:
BioMed Central Ltd
Citation:
Hulur et al. BMC Genomics (2015) 16:138 DOI 10.1186/s12864-015-1292-z
Journal:
BMC Genomics
Rights:
© 2015 Hulur et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. This study provides a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases. RESULTS: 8.4 million imputed SNPs were tested for their associations with 16,252 expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL, corresponding to 122 independent signals, were identified at a false discovery rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant enrichment for GWAS variants for IBD (Crohn's disease [CD] and ulcerative colitis [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3, INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD-associated variants. The CRC-associated eQTL rs3802842 was associated with the expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription start sites and for active histone marks was demonstrated, and eQTL with high population differentiation were identified. CONCLUSIONS: Through the comprehensive study of eQTL in the human colon, this study identified novel target genes for IBD- and CRC-associated genetic variants. Moreover, bioinformatic characterization of colon eQTL provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups.
EISSN:
1471-2164
DOI:
10.1186/s12864-015-1292-z
Keywords:
Expression quantitative trait loci; Colon; Gene expression; African Americans; Regulatory variation; Transcriptomics; Inflammatory bowel disease; Colorectal cancer; Genomics; Genome-wide association studies
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2164/16/138

Full metadata record

DC FieldValue Language
dc.contributor.authorHulur, Imgeen
dc.contributor.authorGamazon, Eric R.en
dc.contributor.authorSkol, Andrew D.en
dc.contributor.authorXicola, Rosa M.en
dc.contributor.authorLlor, Xavieren
dc.contributor.authorOnel, Kenanen
dc.contributor.authorEllis, Nathan A.en
dc.contributor.authorKupfer, Sonia S.en
dc.date.accessioned2016-05-20T09:03:15Z-
dc.date.available2016-05-20T09:03:15Z-
dc.date.issued2015en
dc.identifier.citationHulur et al. BMC Genomics (2015) 16:138 DOI 10.1186/s12864-015-1292-zen
dc.identifier.doi10.1186/s12864-015-1292-zen
dc.identifier.urihttp://hdl.handle.net/10150/610285-
dc.description.abstractBACKGROUND: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with diseases of the colon including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). However, the functional role of many of these SNPs is largely unknown and tissue-specific resources are lacking. Expression quantitative trait loci (eQTL) mapping identifies target genes of disease-associated SNPs. This study provides a comprehensive eQTL map of distal colonic samples obtained from 40 healthy African Americans and demonstrates their relevance for GWAS of colonic diseases. RESULTS: 8.4 million imputed SNPs were tested for their associations with 16,252 expression probes representing 12,363 unique genes. 1,941 significant cis-eQTL, corresponding to 122 independent signals, were identified at a false discovery rate (FDR) of 0.01. Overall, among colon cis-eQTL, there was significant enrichment for GWAS variants for IBD (Crohn's disease [CD] and ulcerative colitis [UC]) and CRC as well as type 2 diabetes and body mass index. ERAP2, ADCY3, INPP5E, UBA7, SFMBT1, NXPE1 and REXO2 were identified as target genes for IBD-associated variants. The CRC-associated eQTL rs3802842 was associated with the expression of C11orf93 (COLCA2). Enrichment of colon eQTL near transcription start sites and for active histone marks was demonstrated, and eQTL with high population differentiation were identified. CONCLUSIONS: Through the comprehensive study of eQTL in the human colon, this study identified novel target genes for IBD- and CRC-associated genetic variants. Moreover, bioinformatic characterization of colon eQTL provides a tissue-specific tool to improve understanding of biological differences in diseases between different ethnic groups.en
dc.language.isoenen
dc.publisherBioMed Central Ltden
dc.relation.urlhttp://www.biomedcentral.com/1471-2164/16/138en
dc.rights© 2015 Hulur et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)en
dc.subjectExpression quantitative trait locien
dc.subjectColonen
dc.subjectGene expressionen
dc.subjectAfrican Americansen
dc.subjectRegulatory variationen
dc.subjectTranscriptomicsen
dc.subjectInflammatory bowel diseaseen
dc.subjectColorectal canceren
dc.subjectGenomicsen
dc.subjectGenome-wide association studiesen
dc.titleEnrichment of inflammatory bowel disease and colorectal cancer risk variants in colon expression quantitative trait locien
dc.typeArticleen
dc.identifier.eissn1471-2164en
dc.contributor.departmentCommittee on Genetics, Genomics and Systems Biology, University of Chicagoen
dc.contributor.departmentDepartment of Medicine, University of Chicagoen
dc.contributor.departmentDepartment of Pediatrics, University of Chicagoen
dc.contributor.departmentDepartment of Medicine, Yale Universityen
dc.contributor.departmentUniversity of Arizona Cancer Centeren
dc.contributor.departmentDivision of Genetic Medicine, Department of Medicine, Vanderbilt Universityen
dc.identifier.journalBMC Genomicsen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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