Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NsCLC)risk.biological mechanisms of these variants remain largely *** integrating a...
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Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NsCLC)risk.biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(sqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk.variants for NsCLC,which were overrepresented in enhancer-lik. and promoter-lik. histone modification peak. as well as DNase I hypersensitive *** factor enrichment analysis revealed that UsF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for sqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while sqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NsCLC,providing not only novel insights into the genetic heterogeneity between AD and sqCC but also a set of plausible gene targets for post-GWAs functional experiments.
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