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

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

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

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 and Ulrike Peters

PLOS ONE, 2012, vol. 7, issue 12, 1-14

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

Date: 2012
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0052535

DOI: 10.1371/journal.pone.0052535

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