Weak sharing of genetic association signals in three lung cancer subtypes: evidence at the SNP, gene, regulation, and pathway levels

Genome Medicine
Timothy D O'BrienZhongming Zhao

Abstract

There are two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC has many subtypes, but the two most common are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). These subtypes are mainly classified by physiological and pathological characteristics, although there is increasing evidence of genetic and molecular differences as well. Although some work has been done at the somatic level to explore the genetic and biological differences among subtypes, little work has been done that interrogates these differences at the germline level to characterize the unique and shared susceptibility genes for each subtype. We used single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) of European samples to interrogate the similarity of the subtypes at the SNP, gene, pathway, and regulatory levels. We expanded these genotyped SNPs to include all SNPs in linkage disequilibrium (LD) using data from the 1000 Genomes Project. We mapped these SNPs to several lung tissue expression quantitative trait loci (eQTL) and enhancer datasets to identify regulatory SNPs and their target genes. We used these genes to perform a biological pathway analysis for each...Continue Reading

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Citations

Jun 5, 2018·Human Heredity·Timothy D O'BrienZhongming Zhao
May 19, 2021·NPJ Precision Oncology·Sipeng ShenDavid C Christiani
Nov 2, 2021·Cell Transplantation·Qi-Shun GengJie Zhao

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Methods Mentioned

BETA
genotyping
chip
PCA
GTPase

Software Mentioned

biomaRt
Affymetrix
WEB
bedtools
PET
FANTOM5
Promoter Enhancer Slider Selector Tool ( PrESSTo )
Remap
GTEx
IM

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