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

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Author
Jiao, Shuo
Hsu, Li
Berndt, Sonja
Bézieau, Stéphane
Brenner, Hermann
Buchanan, Daniel
Caan, Bette J.
Campbell, Peter T.
Carlson, Christopher S.
Casey, Graham
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
Le Marchand, Loic
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
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0052535Metadata
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Jiao, Shuo, Li Hsu, Sonja Berndt, Stéphane Bézieau, Hermann Brenner, Daniel Buchanan, Bette J. Caan, et al. 2012. Genome-wide search for gene-gene interactions in colorectal cancer. PLoS ONE 7(12): e52535.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<\(10^{−4}\)). For the known locus rs10795668 (10p14), we found an interacting SNP rs367615 (5q21) with replication p = 0.01 and combined p = 4.19×\(10^{−8}\). Among the top marginal SNPs after LD pruning (n = 163), we identified an interaction between rs1571218 (20p12.3) and rs10879357 (12q21.1) (nominal combined p = 2.51×\(10^{−6}\); Bonferroni adjusted p = 0.03). Our study represents the first comprehensive search for GxG in CRC, and our results may provide new insight into the genetic etiology of CRC.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530500/pdf/Terms of Use
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