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Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer

Author

Listed:
  • Shuo Jiao
  • Li Hsu
  • Sonja Berndt
  • Stéphane Bézieau
  • Hermann Brenner
  • Daniel Buchanan
  • Bette J Caan
  • Peter T Campbell
  • Christopher S Carlson
  • Graham Casey
  • Andrew T Chan
  • Jenny Chang-Claude
  • Stephen Chanock
  • David V Conti
  • Keith R Curtis
  • David Duggan
  • Steven Gallinger
  • Stephen B Gruber
  • Tabitha A Harrison
  • Richard B Hayes
  • Brian E Henderson
  • Michael Hoffmeister
  • John L Hopper
  • Thomas J Hudson
  • Carolyn M Hutter
  • Rebecca D Jackson
  • Mark A Jenkins
  • Elizabeth D Kantor
  • Laurence N Kolonel
  • Sébastien Küry
  • Loic Le Marchand
  • Mathieu Lemire
  • Polly A Newcomb
  • John D Potter
  • Conghui Qu
  • Stephanie A Rosse
  • Robert E Schoen
  • Fred R Schumacher
  • Daniela Seminara
  • Martha L Slattery
  • Cornelia M Ulrich
  • Brent W Zanke
  • Ulrike Peters

Abstract

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to Interaction (ARDI). With this method, we conducted a genome-wide search to identify SNPs showing evidence for GxG with previously identified CRC susceptibility loci from 14 independent regions. We also conducted a genome-wide search for GxG using the marginal association screening and examining interaction among SNPs that pass the screening threshold (p

Suggested Citation

  • Shuo Jiao & Li Hsu & Sonja Berndt & Stéphane Bézieau & Hermann Brenner & Daniel Buchanan & Bette J Caan & Peter T Campbell & Christopher S Carlson & Graham Casey & Andrew T Chan & Jenny Chang-Claude &, 2012. "Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-14, December.
    • Handle: RePEc:plo:pone00:0052535
    DOI: 10.1371/journal.pone.0052535
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    References listed on IDEAS

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    1. David E. Reich & Michele Cargill & Stacey Bolk & James Ireland & Pardis C. Sabeti & Daniel J. Richter & Thomas Lavery & Rose Kouyoumjian & Shelli F. Farhadian & Ryk Ward & Eric S. Lander, 2001. "Linkage disequilibrium in the human genome," Nature, Nature, vol. 411(6834), pages 199-204, May.
    2. Yang Liu & Haiming Xu & Suchao Chen & Xianfeng Chen & Zhenguo Zhang & Zhihong Zhu & Xueying Qin & Landian Hu & Jun Zhu & Guo-Ping Zhao & Xiangyin Kong, 2011. "Genome-Wide Interaction-Based Association Analysis Identified Multiple New Susceptibility Loci for Common Diseases," PLOS Genetics, Public Library of Science, vol. 7(3), pages 1-16, March.
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    1. Luis M Real & Agustín Ruiz & Javier Gayán & Antonio González-Pérez & María E Sáez & Reposo Ramírez-Lorca & Francisco J Morón & Juan Velasco & Ruth Marginet-Flinch & Eva Musulén & José M Carrasco & Con, 2014. "A Colorectal Cancer Susceptibility New Variant at 4q26 in the Spanish Population Identified by Genome-Wide Association Analysis," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-11, June.

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