Journal Article

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

McLaughlin, John, Bierut, Laura J, Koh, Woon-Puay, Hu, Zhibin, Hung, Rayjean J, Johansen, Jakob S, Beesley, Jonathan, Chen, Chu, Brüske, Irene, Thorgeirsson, Thorgeir E, Zienolddiny, Shanbeh, Amos, Christopher I, Swiatkowska, Beata, Bertazzi, Pier Alberto, Rafnar, Thorunn, Tsao, Ming-Sound, Song, Lei, Risch, Angela, Duell, Eric J, Woll, Penella, Fernandez-Tardon, Guillermo, Stevens, Victoria L, Orlowski, Tadeusz M, Muley, Thomas R, Stefansson, Kari, Haura, Eric B, Hong, Yun-Chul, Li, Yafang, Ji, Xuemei, Han, Younghun, Ye, Yuanqing, Saliba, Walid, Obeidat, Ma'en, Kamal, Ahsan, Leighl, Natasha, Manz, Judith, Ognjanovic, Simona, Lindströem, Sara, Albanes, Demetrios, Kachuri, Linda, Tobin, Martin D, Christiani, David C, Shen, Hongbing, McKay, James D, Andrew, Angeline S, Shepherd, Frances A, Zong, Xuchen, Field, John K, Xiao, Xiangjun, Bolca, Ciprian, Lazarus, Philip, Spitz, Margaret R, Holcatova, Ivana, Timens, Wim, Carreras-Torres, Robert, Wu, Xifeng, Johansson, Mattias, Reginsson, Gunnar W, Dunning, Alison, Le Marchand, Loic, van der Heijden, Henricus F M, Landi, Maria Teresa, Bickeböller, Heike, Caporaso, Nei

2017

Overview

Christopher Amos and colleagues perform genome-wide association analysis for lung cancer using cohorts genotyped on the OncoArray and combing these with existing data. They identify 18 loci, 10 of which are new, finding heterogeneity across the different lung cancer subtypes, and explore candidate genes through eQTL analysis in lung tissue. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 38 / 38/91 / 45 / 45/43 / 45/61 / 631/208/205/2138 / 631/61/212/2019 / 631/67/1612 / Adenocarcinoma / Adenocarcinoma - genetics / Adenocarcinoma of Lung / Adult / Aged / Agriculture / Animal Genetics and Genomics / Association analysis / Biomedicine / Cancer / Cancer and Oncology / Cancer och onkologi / Cancer Research / Care and treatment / Chromosome Mapping / Chronic obstructive pulmonary disease / Clinical Medicine / Consortia / Development and progression / Disease / Etiology / Family Health / Female / Gene expression / Gene Function / Gene mapping / Genealogy / Genes / Genetic aspects / Genetic Predisposition to Disease / Genome-wide association studies / Genome-Wide Association Study / Genomes / Genotype / Health aspects / Heritability / Heterogeneity / Human Genetics / Humans / Klinisk medicin / letter / Lung cancer / Lung Neoplasms - epidemiology / Lung Neoplasms - ethnology / Lung Neoplasms - genetics / Male / Medical and Health Sciences / Medicin och hälsovetenskap / Middle Aged / Polymorphism, Single Nucleotide / Quantitative Trait Loci / Smoking / Smoking - epidemiology / Studies / Telomere Homeostasis - genetics / Transcriptomics / White People - genetics