Transcriptome-wide association study reveals candidate causal genes for lung cancer.
Publication Title
International journal of cancer. Journal international du cancer
Document Type
Article
Publication Date
4-1-2020
Keywords
Biomarkers, Tumor; Cell Line, Tumor; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lung Neoplasms; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Transcriptome
Abstract
We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (p
Area of Special Interest
Cancer
Specialty/Research Institute
Oncology
