title: Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus.
abstract: BACKGROUND
  Gene-set analysis (GSA) is an approach using the results of single-marker genome-wide association studies when investigating pathways as a whole with respect to the genetic basis of a disease.
  
  
  METHODS
  We performed a meta-analysis of seven GSAs for lung cancer, applying the method META-GSA. Overall, the information taken from 11,365 cases and 22,505 controls from within the TRICL/ILCCO consortia was used to investigate a total of 234 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.
  
  
  RESULTS
  META-GSA reveals the systemic lupus erythematosus KEGG pathway hsa05322, driven by the gene region 6p21-22, as also implicated in lung cancer (p = 0.0306). This gene region is known to be associated with squamous cell lung carcinoma. The most important genes driving the significance of this pathway belong to the genomic areas HIST1-H4L, -1BN, -2BN, -H2AK, -H4K and C2/C4A/C4B. Within these areas, the markers most significantly associated with LC are rs13194781 (located within HIST12BN) and rs1270942 (located between C2 and C4A).
  
  
  CONCLUSIONS
  We have discovered a pathway currently marked as specific to systemic lupus erythematosus as being significantly implicated in lung cancer. The gene region 6p21-22 in this pathway appears to be more extensively associated with lung cancer than previously assumed. Given wide-stretched linkage disequilibrium to the area APOM/BAG6/MSH5, there is currently simply not enough information or evidence to conclude whether the potential pleiotropy of lung cancer and systemic lupus erythematosus is spurious, biological, or mediated. Further research into this pathway and gene region will be necessary.
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Albert
authors.identifier: http://orcid.org/0000-0001-7848-1332
authors.initials: A
authors.lastname: Rosenberger
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Sohns
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Friedrichs
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
authors.forename: Gord
authors.initials: G
authors.lastname: Fehringer
authors.affiliation: Public Health Ontario, Toronto, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Division of Molecular Biology, University Salzburg, Salzburg, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Institute of Epidemiology I, Helmholtz Center Munich, Munich, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Brüske
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Harvard University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Harvard University School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeböller
mesh_terms: D016022:Case-Control Studies; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D015870:Gene Expression; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D015398:Signal Transduction