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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer

Byun, J. ; Melander, O. LU orcid ; Brunnstrom, H. LU orcid and Amos, C.I. (2022) In Nature Genetics 54(8). p.1167-1177
Abstract
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung... (More)
To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc. (Less)
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Contribution to journal
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published
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keywords
DNA binding protein, FUBP1 protein, human, RNA binding protein, genetic predisposition, genetics, genome-wide association study, human, lung tumor, meta analysis, quantitative trait locus, single nucleotide polymorphism, DNA-Binding Proteins, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lung Neoplasms, Polymorphism, Single Nucleotide, Quantitative Trait Loci, RNA-Binding Proteins
in
Nature Genetics
volume
54
issue
8
pages
11 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85135272569
  • pmid:35915169
ISSN
1061-4036
DOI
10.1038/s41588-022-01115-x
language
English
LU publication?
yes
id
3e3e0ce2-754d-4752-9947-4e1b68ab030f
date added to LUP
2022-09-16 11:26:54
date last changed
2024-01-16 02:32:35
@article{3e3e0ce2-754d-4752-9947-4e1b68ab030f,
  abstract     = {{To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.}},
  author       = {{Byun, J. and Melander, O. and Brunnstrom, H. and Amos, C.I.}},
  issn         = {{1061-4036}},
  keywords     = {{DNA binding protein; FUBP1 protein, human; RNA binding protein; genetic predisposition; genetics; genome-wide association study; human; lung tumor; meta analysis; quantitative trait locus; single nucleotide polymorphism; DNA-Binding Proteins; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lung Neoplasms; Polymorphism, Single Nucleotide; Quantitative Trait Loci; RNA-Binding Proteins}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1167--1177}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer}},
  url          = {{http://dx.doi.org/10.1038/s41588-022-01115-x}},
  doi          = {{10.1038/s41588-022-01115-x}},
  volume       = {{54}},
  year         = {{2022}},
}