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Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus

Author

Listed:
  • Albert Rosenberger
  • Melanie Sohns
  • Stefanie Friedrichs
  • Rayjean J Hung
  • Gord Fehringer
  • John McLaughlin
  • Christopher I Amos
  • Paul Brennan
  • Angela Risch
  • Irene Brüske
  • Neil E Caporaso
  • Maria Teresa Landi
  • David C Christiani
  • Yongyue Wei
  • Heike Bickeböller

Abstract

Introduction: 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.

Suggested Citation

  • Albert Rosenberger & Melanie Sohns & Stefanie Friedrichs & Rayjean J Hung & Gord Fehringer & John McLaughlin & Christopher I Amos & Paul Brennan & Angela Risch & Irene Brüske & Neil E Caporaso & Maria, 2017. "Gene-set meta-analysis of lung cancer identifies pathway related to systemic lupus erythematosus," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-14, March.
    • Handle: RePEc:plo:pone00:0173339
    DOI: 10.1371/journal.pone.0173339
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    References listed on IDEAS

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    1. Gordon Fehringer & Geoffrey Liu & Laurent Briollais & Paul Brennan & Christopher I Amos & Margaret R Spitz & Heike Bickeböller & H Erich Wichmann & Angela Risch & Rayjean J Hung, 2012. "Comparison of Pathway Analysis Approaches Using Lung Cancer GWAS Data Sets," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-8, February.
    2. Albert Rosenberger & Stefanie Friedrichs & Christopher I Amos & Paul Brennan & Gordon Fehringer & Joachim Heinrich & Rayjean J Hung & Thomas Muley & Martina Müller-Nurasyid & Angela Risch & Heike Bick, 2015. "META-GSA: Combining Findings from Gene-Set Analyses across Several Genome-Wide Association Studies," PLOS ONE, Public Library of Science, vol. 10(10), pages 1-21, October.
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