Back to Search Start Over

eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma.

Authors :
Xiaoyu Wang
Gharahkhani, Puya
Levine, David M.
Fitzgerald, Rebecca C.
Gockel, Ines
Corley, Douglas A.
Risch, Harvey A.
Bernstein, Leslie
Wong-Ho Chow
Onstad, Lynn
Shaheen, Nicholas J.
Lagergren, Jesper
Hardie, Laura J.
Wu, Anna H.
Pharoah, Paul D. P.
Liu, Geoffrey
Anderson, Lesley A.
Iyer, Prasad G.
Gammon, Marilie D.
Caldas, Carlos
Source :
Cancer Epidemiology, Biomarkers & Prevention; Sep2022, Vol. 31 Issue 9, p1735-1745, 11p
Publication Year :
2022

Abstract

Background: Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. Results: Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10559965
Volume :
31
Issue :
9
Database :
Supplemental Index
Journal :
Cancer Epidemiology, Biomarkers & Prevention
Publication Type :
Academic Journal
Accession number :
159018625
Full Text :
https://doi.org/10.1158/1055-9965.EPI-22-0096