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

James D McKay; Rayjean J Hung; Younghun Han; Xuchen Zong; Robert Carreras-Torres; David C Christiani; Neil E Caporaso; Mattias Johansson; Xiangjun Xiao; Yafang Li; Jinyoung Byun; Alison Dunning; Karen A Pooley; David C Qian; Xuemei Ji; Geoffrey Liu; Maria N Timofeeva; Stig E Bojesen; Xifeng Wu; Loic Le Marchand; Demetrios Albanes; Heike Bickeböller; Melinda C Aldrich; William S Bush; Adonina Tardon; Gad Rennert; M Dawn Teare; John K Field; Lambertus A Kiemeney; Philip Lazarus; Aage Haugen; Stephen Lam; Matthew B Schabath; Angeline S Andrew; Hongbing Shen; Yun-Chul Hong; Jian-Min Yuan; Pier Alberto Bertazzi; Angela C Pesatori; Yuanqing Ye; Nancy Diao; Li Su; Ruyang Zhang; Yonathan Brhane; Natasha Leighl; Jakob S Johansen; Anders Mellemgaard; Walid Saliba; Christopher A Haiman; Lynne R Wilkens; SpiroMeta Consortium

doi:10.1038/ng.3892

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

James D McKay, Rayjean J Hung, Younghun Han, Xuchen Zong, Robert Carreras-Torres, David C Christiani, Neil E Caporaso, Mattias Johansson, Xiangjun Xiao, Yafang Li, Jinyoung Byun, Alison Dunning, Karen A Pooley, David C Qian, Xuemei Ji, Geoffrey Liu, Maria N Timofeeva, Stig E Bojesen, Xifeng Wu, Loic Le MarchandDemetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Hongbing Shen, Yun-Chul Hong, Jian-Min Yuan, Pier Alberto Bertazzi, Angela C Pesatori, Yuanqing Ye, Nancy Diao, Li Su, Ruyang Zhang, Yonathan Brhane, Natasha Leighl, Jakob S Johansen, Anders Mellemgaard, Walid Saliba, Christopher A Haiman, Lynne R Wilkens, SpiroMeta Consortium

484 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	49
Udgave nummer	7
Sider (fra-til)	1126-1132
Antal sider	7
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.3892
Status	Udgivet - jul. 2017

Adgang til dokumentet

10.1038/ng.3892

Citationsformater

McKay, J. D., Hung, R. J., Han, Y., Zong, X., Carreras-Torres, R., Christiani, D. C., Caporaso, N. E., Johansson, M., Xiao, X., Li, Y., Byun, J., Dunning, A., Pooley, K. A., Qian, D. C., Ji, X., Liu, G., Timofeeva, M. N., Bojesen, S. E., Wu, X., ... SpiroMeta Consortium (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. https://doi.org/10.1038/ng.3892

McKay, JD, Hung, RJ, Han, Y, Zong, X, Carreras-Torres, R, Christiani, DC, Caporaso, NE, Johansson, M, Xiao, X, Li, Y, Byun, J, Dunning, A, Pooley, KA, Qian, DC, Ji, X, Liu, G, Timofeeva, MN, Bojesen, SE, Wu, X, Le Marchand, L, Albanes, D, Bickeböller, H, Aldrich, MC, Bush, WS, Tardon, A, Rennert, G, Teare, MD, Field, JK, Kiemeney, LA, Lazarus, P, Haugen, A, Lam, S, Schabath, MB, Andrew, AS, Shen, H, Hong, Y-C, Yuan, J-M, Bertazzi, PA, Pesatori, AC, Ye, Y, Diao, N, Su, L, Zhang, R, Brhane, Y, Leighl, N, Johansen, JS, Mellemgaard, A, Saliba, W, Haiman, CA, Wilkens, LR & SpiroMeta Consortium 2017, 'Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes', Nature Genetics, bind 49, nr. 7, s. 1126-1132. https://doi.org/10.1038/ng.3892

@article{bf4122d11428474a9ec206daae86e7c9,

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

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.",

keywords = "Adenocarcinoma, Adult, Aged, Chromosome Mapping, European Continental Ancestry Group, Family Health, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Lung Neoplasms, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Smoking, Telomere Homeostasis, Journal Article, Meta-Analysis",

author = "McKay, {James D} and Hung, {Rayjean J} and Younghun Han and Xuchen Zong and Robert Carreras-Torres and Christiani, {David C} and Caporaso, {Neil E} and Mattias Johansson and Xiangjun Xiao and Yafang Li and Jinyoung Byun and Alison Dunning and Pooley, {Karen A} and Qian, {David C} and Xuemei Ji and Geoffrey Liu and Timofeeva, {Maria N} and Bojesen, {Stig E} and Xifeng Wu and {Le Marchand}, Loic and Demetrios Albanes and Heike Bickeb{\"o}ller and Aldrich, {Melinda C} and Bush, {William S} and Adonina Tardon and Gad Rennert and Teare, {M Dawn} and Field, {John K} and Kiemeney, {Lambertus A} and Philip Lazarus and Aage Haugen and Stephen Lam and Schabath, {Matthew B} and Andrew, {Angeline S} and Hongbing Shen and Yun-Chul Hong and Jian-Min Yuan and Bertazzi, {Pier Alberto} and Pesatori, {Angela C} and Yuanqing Ye and Nancy Diao and Li Su and Ruyang Zhang and Yonathan Brhane and Natasha Leighl and Johansen, {Jakob S} and Anders Mellemgaard and Walid Saliba and Haiman, {Christopher A} and Wilkens, {Lynne R} and {SpiroMeta Consortium}",

year = "2017",

month = jul,

doi = "10.1038/ng.3892",

language = "English",

volume = "49",

pages = "1126--1132",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "7",

}

TY - JOUR

T1 - Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

AU - McKay, James D

AU - Hung, Rayjean J

AU - Han, Younghun

AU - Zong, Xuchen

AU - Carreras-Torres, Robert

AU - Christiani, David C

AU - Caporaso, Neil E

AU - Johansson, Mattias

AU - Xiao, Xiangjun

AU - Li, Yafang

AU - Byun, Jinyoung

AU - Dunning, Alison

AU - Pooley, Karen A

AU - Qian, David C

AU - Ji, Xuemei

AU - Liu, Geoffrey

AU - Timofeeva, Maria N

AU - Bojesen, Stig E

AU - Wu, Xifeng

AU - Le Marchand, Loic

AU - Albanes, Demetrios

AU - Bickeböller, Heike

AU - Aldrich, Melinda C

AU - Bush, William S

AU - Tardon, Adonina

AU - Rennert, Gad

AU - Teare, M Dawn

AU - Field, John K

AU - Kiemeney, Lambertus A

AU - Lazarus, Philip

AU - Haugen, Aage

AU - Lam, Stephen

AU - Schabath, Matthew B

AU - Andrew, Angeline S

AU - Shen, Hongbing

AU - Hong, Yun-Chul

AU - Yuan, Jian-Min

AU - Bertazzi, Pier Alberto

AU - Pesatori, Angela C

AU - Ye, Yuanqing

AU - Diao, Nancy

AU - Su, Li

AU - Zhang, Ruyang

AU - Brhane, Yonathan

AU - Leighl, Natasha

AU - Johansen, Jakob S

AU - Mellemgaard, Anders

AU - Saliba, Walid

AU - Haiman, Christopher A

AU - Wilkens, Lynne R

AU - SpiroMeta Consortium

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - Adenocarcinoma

KW - Adult

KW - Aged

KW - Chromosome Mapping

KW - European Continental Ancestry Group

KW - Family Health

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Lung Neoplasms

KW - Male

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Smoking

KW - Telomere Homeostasis

KW - Journal Article

KW - Meta-Analysis

U2 - 10.1038/ng.3892

DO - 10.1038/ng.3892

M3 - Journal article

C2 - 28604730

SN - 1061-4036

VL - 49

SP - 1126

EP - 1132

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

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

Abstract

Adgang til dokumentet

Fingeraftryk

Citationsformater