Publication Title

Nature genetics

Authors

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
Ana Fernandez-Somoano
Guillermo Fernandez-Tardon
Henricus F M van der Heijden
Jin Hee Kim
Juncheng Dai
Zhibin Hu
Michael P A Davies
Michael W Marcus
Hans Brunnström
Jonas Manjer
Olle Melander
David C Muller
Kim Overvad
Antonia Trichopoulou
Rosario Tumino
Jennifer A Doherty
Matt P Barnett
Chu Chen
Gary E Goodman, Swedish Medical Group, Seattle, WAFollow
Angela Cox
Fiona Taylor
Penella Woll
Irene Brüske
H-Erich Wichmann
Judith Manz
Thomas R Muley
Angela Risch
Albert Rosenberger
Kjell Grankvist
Mikael Johansson
Frances A Shepherd
Ming-Sound Tsao
Susanne M Arnold
Eric B Haura
Ciprian Bolca
Ivana Holcatova
Vladimir Janout
Milica Kontic
Jolanta Lissowska
Anush Mukeria
Simona Ognjanovic
Tadeusz M Orlowski
Ghislaine Scelo
Beata Swiatkowska
David Zaridze
Per Bakke
Vidar Skaug
Shanbeh Zienolddiny
Eric J Duell
Lesley M Butler
Woon-Puay Koh
Yu-Tang Gao
Richard S Houlston
John McLaughlin
Victoria L Stevens
Philippe Joubert
Maxime Lamontagne
David C Nickle
Ma'en Obeidat
Wim Timens
Bin Zhu
Lei Song
Linda Kachuri
María Soler Artigas
Martin D Tobin
Louise V Wain
Thorunn Rafnar
Thorgeir E Thorgeirsson
Gunnar W Reginsson
Kari Stefansson
Dana B Hancock
Laura J Bierut
Margaret R Spitz
Nathan C Gaddis
Sharon M Lutz
Fangyi Gu
Eric O Johnson
Ahsan Kamal
Claudio Pikielny
Dakai Zhu
Sara Lindströem
Xia Jiang
Rachel F Tyndale
Georgia Chenevix-Trench
Jonathan Beesley
Yohan Bossé
Stephen Chanock
Paul Brennan
Maria Teresa Landi
Christopher I Amos

Document Type

Article

Publication Date

7-1-2017

Keywords

Adenocarcinoma; Adenocarcinoma of Lung; 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

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.

Clinical Institute

Cancer

Specialty

Oncology

Specialty

Pulmonary Medicine

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