Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
Author(s)
Type
Journal Article
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.
Date Issued
2017-07-01
Date Acceptance
2017-05-10
Citation
Nature Genetics, 2017, 49 (7), pp.1126-1132
ISSN
1061-4036
Publisher
Nature Publishing Group
Start Page
1126
End Page
1132
Journal / Book Title
Nature Genetics
Volume
49
Issue
7
Copyright Statement
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404253300024&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
TELOMERE LENGTH
CROHNS-DISEASE
COMMON CANCERS
GLIOMA RISK
VARIANTS
IMPUTATION
ARCHITECTURE
METAANALYSIS
CONSORTIUM
Publication Status
Published
Date Publish Online
2017-06-12