Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

McKay, JD, Hung, RJ, Han, Y, Zong, X, Carreras-Torres, R, Christiani, DC, Caporaso, NE, Johansson, M, Xiao, X and Field, JK ORCID: 0000-0003-3951-6365 (2017) Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nature Genetics, 49 (7). 1126 - 1132.

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Abstract

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

Item Type:	Article
Uncontrolled Keywords:	Genome-wide association studies, Lung cancer, Transcriptomics
Depositing User:	Symplectic Admin
Date Deposited:	23 Jan 2018 09:23
Last Modified:	19 Jan 2023 06:42
DOI:	10.1038/ng.3892
Open Access URL:	https://www.nature.com/articles/ng.3892
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3016684