Title: Positional integration of lung adenocarcinoma susceptibility loci with primary human alveolar epithelial cell epigenomes.
Authors: Yang, Chenchen; Stueve, Theresa Ryan; Yan, Chunli; Rhie, Suhn K; Mullen, Daniel J; Luo, Jiao; Zhou, Beiyun; Borok, Zea; Marconett, Crystal N; Offringa, Ite A
Published In Epigenomics, (2018 09)
Abstract: To identify functional lung adenocarcinoma (LUAD) risk SNPs.Eighteen validated LUAD risk SNPs (p ≤ 5 × 10-8) and 930 SNPs in high linkage disequilibrium (r2 > 0.5) were integrated with epigenomic information from primary human alveolar epithelial cells. Enhancer-associated SNPs likely affecting transcription factor-binding sites were predicted. Three SNPs were functionally investigated using luciferase assays, expression quantitative trait loci and cancer-specific expression.Forty-seven SNPs mapped to putative enhancers; 11 located to open chromatin. Of these, seven altered predicted transcription factor-binding motifs. Rs6942067 showed allele-specific luciferase expression and expression quantitative trait loci analysis indicates that it influences expression of DCBLD1, a gene that encodes an unknown membrane protein and is overexpressed in LUAD.Integration of candidate LUAD risk SNPS with epigenomic marks from normal alveolar epithelium identified numerous candidate functional LUAD risk SNPs including rs6942067, which appears to affect DCBLD1 expression. Data deposition: Data are provided in GEO record GSE84273.
PubMed ID: 30212242
MeSH Terms: Adenocarcinoma/genetics*; Alveolar Epithelial Cells/cytology; Alveolar Epithelial Cells/metabolism*; Enhancer Elements, Genetic/genetics*; Epigenesis, Genetic*; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Linkage Disequilibrium; Lung Neoplasms/genetics*; Male; Membrane Proteins/biosynthesis; Membrane Proteins/genetics*; Middle Aged; Polymorphism, Single Nucleotide*; Quantitative Trait Loci