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Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Ji, Xuemei; Brunnström, Hans LU ; Manjer, Jonas LU ; Melander, Olle LU ; Overvad, Kim; Amos, Christopher I and , (2018) In Nature Communications 9(1).
Abstract
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer... (More)
Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer. © 2018, The Author(s). (Less)
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organization
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Contribution to journal
publication status
published
subject
in
Nature Communications
volume
9
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85051632965
ISSN
2041-1723
DOI
10.1038/s41467-018-05074-y
language
English
LU publication?
yes
id
1047e608-12e3-4f81-a538-f28059dbd862
date added to LUP
2018-09-06 09:48:44
date last changed
2019-06-11 03:52:25
@article{1047e608-12e3-4f81-a538-f28059dbd862,
  abstract     = {Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer. © 2018, The Author(s).},
  articleno    = {3221},
  author       = {Ji, Xuemei and Brunnström, Hans and Manjer, Jonas and Melander, Olle and Overvad, Kim and Amos, Christopher I and , },
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk},
  url          = {http://dx.doi.org/10.1038/s41467-018-05074-y},
  volume       = {9},
  year         = {2018},
}