Schroeder, Julia, Schueller, Vitalia, May, Andrea, Gerges, Christian, Anders, Mario, Becker, Jessica, Hess, Timo, Kreuser, Nicole, Thieme, Rene ORCID: 0000-0002-0537-3979, Ludwig, Kerstin U., Noder, Tania, Venerito, Marino, Veits, Lothar, Schmidt, Thomas ORCID: 0000-0002-7166-3675, Fuchs, Claudia, Izbicki, Jakob R., Hoelscher, Arnulf H., Dakkak, Dani, Jansen-Winkeln, Boris, Moulla, Yusef, Lyros, Orestis, Niebisch, Stefan, Mehdorn, Matthias, Lang, Hauke, Lorenz, Dietmar, Schumacher, Brigitte, Mayershofer, Rupert, Vashist, Yogesh, Ott, Katja, Vieth, Michael, Weismueller, Josef, Mangold, Elisabeth, Noethen, Markus M., Moebus, Susanne, Knapp, Michael, Neuhaus, Horst, Roesch, Thomas, Ell, Christian, Gockel, Ines, Schumacher, Johannes and Boehmer, Anne C. (2019). Identification of loci of functional relevance to Barrett's esophagus and esophageal adenocarcinoma: Cross-referencing of expression quantitative trait loci data from disease-relevant tissues with genetic association data. PLoS One, 14 (12). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Full text not available from this repository.

Abstract

Esophageal adenocarcinoma (EA) and its precancerous condition Barrett's esophagus (BE) are multifactorial diseases with rising prevalence rates in Western populations. A recent meta -analysis of genome-wide association studies (GWAS) data identified 14 BE/EA risk loci located in non-coding genomic regions. Knowledge about the impact of non-coding variation on disease pathology is incomplete and needs further investigation. The aim of the present study was (i) to identify candidate genes of functional relevance to BE/EA at known risk loci and (ii) to find novel risk loci among the suggestively associated variants through the integration of expression quantitative trait loci (eQTL) and genetic association data. eQTL data from two BE/EA-relevant tissues (esophageal mucosa and gastroesophageal junction) generated within the context of the GTEx project were cross-referenced with the GWAS meta-analysis data. Variants representing an eQTL in at least one of the two tissues were categorized into genome-wide significant loci (P < 5x10(-8)) and novel candidate loci (5x10(-8) <= P <= 5x10(-5)). To follow up these novel candidate loci, a genetic association study was performed in a replication cohort comprising 1,993 cases and 967 controls followed by a combined analysis with the GWAS meta-analysis data. The cross-referencing of eQTL and genetic data yielded 2,180 variants that represented 25 loci. Among the previously reported genome-wide significant loci, 22 eQTLs were identified in esophageal mucosa and/or gastroesophageal junction tissue. The regulated genes, most of which have not been linked to BE/EA etiology so far, included C2orf43/LDAH, ZFP57, and SLC9A3. Among the novel candidate loci, replication was achieved for two variants (rs7754014, P-combined = 3.16x10(-7) and rs1540, P-combined = 4.16x10(-6)) which represent eQTLs for CFDP1 and SLC22A3, respectively. In summary, the present approach identified candidate genes whose expression was regulated by risk variants in disease-relevant tissues. These findings may facilitate the elucidation of BE/EA pathophysiology.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schroeder, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schueller, VitaliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
May, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerges, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anders, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuser, NicoleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thieme, ReneUNSPECIFIEDorcid.org/0000-0002-0537-3979UNSPECIFIED
Ludwig, Kerstin U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noder, TaniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Venerito, MarinoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Veits, LotharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, ThomasUNSPECIFIEDorcid.org/0000-0002-7166-3675UNSPECIFIED
Fuchs, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izbicki, Jakob R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoelscher, Arnulf H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dakkak, DaniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jansen-Winkeln, BorisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moulla, YusefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lyros, OrestisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niebisch, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehdorn, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, HaukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorenz, DietmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, BrigitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayershofer, RupertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vashist, YogeshUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ott, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vieth, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weismueller, JosefUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangold, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knapp, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhaus, HorstUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roesch, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ell, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gockel, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boehmer, Anne C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-123786
DOI: 10.1371/journal.pone.0227072
Journal or Publication Title: PLoS One
Volume: 14
Number: 12
Date: 2019
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; CATION TRANSPORTER OCT3; SUSCEPTIBILITY LOCI; BREAST-CANCER; POPULATION; CANDIDATE; RISK; CELL; EQTLMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12378

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item