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. HayesBrian 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

Research output: Contribution to journalArticle

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-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.

Original languageEnglish (US)
Article numbere52535
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 29 2012
Externally publishedYes

Fingerprint

gene interaction
colorectal neoplasms
single nucleotide polymorphism
Single Nucleotide Polymorphism
Colorectal Neoplasms
Polymorphism
Genes
Genome
Nucleotides
genome
genes
loci
Screening
screening
Genome-Wide Association Study
pruning
etiology
heritability
methodology
Testing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jiao, S., Hsu, L., Berndt, S., Bézieau, S., Brenner, H., Buchanan, D., ... Peters, U. (2012). Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer. PLoS One, 7(12), [e52535]. https://doi.org/10.1371/journal.pone.0052535

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; 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.

In: PLoS One, Vol. 7, No. 12, e52535, 29.12.2012.

Research output: Contribution to journalArticle

Jiao, S, Hsu, L, Berndt, S, Bézieau, S, Brenner, H, Buchanan, D, Caan, BJ, Campbell, PT, Carlson, CS, Casey, G, Chan, AT, Chang-Claude, J, Chanock, S, Conti, DV, Curtis, KR, Duggan, D, Gallinger, S, Gruber, SB, Harrison, TA, Hayes, RB, Henderson, BE, Hoffmeister, M, Hopper, JL, Hudson, TJ, Hutter, CM, Jackson, RD, Jenkins, MA, Kantor, ED, Kolonel, LN, Küry, S, Le Marchand, L, Lemire, M, Newcomb, PA, Potter, JD, Qu, C, Rosse, SA, Schoen, RE, Schumacher, FR, Seminara, D, Slattery, ML, Ulrich, CM, Zanke, BW & Peters, U 2012, 'Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer', PLoS One, vol. 7, no. 12, e52535. https://doi.org/10.1371/journal.pone.0052535
Jiao S, Hsu L, Berndt S, Bézieau S, Brenner H, Buchanan D et al. Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer. PLoS One. 2012 Dec 29;7(12). e52535. https://doi.org/10.1371/journal.pone.0052535
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 ; 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. / Genome-Wide Search for Gene-Gene Interactions in Colorectal Cancer. In: PLoS One. 2012 ; Vol. 7, No. 12.
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AU - Jiao, Shuo

AU - Hsu, Li

AU - Berndt, Sonja

AU - Bézieau, Stéphane

AU - Brenner, Hermann

AU - Buchanan, Daniel

AU - Caan, Bette J.

AU - Campbell, Peter T.

AU - Carlson, Christopher S.

AU - Casey, Graham

AU - Chan, Andrew T.

AU - Chang-Claude, Jenny

AU - Chanock, Stephen

AU - Conti, David V.

AU - Curtis, Keith R.

AU - Duggan, David

AU - Gallinger, Steven

AU - Gruber, Stephen B.

AU - Harrison, Tabitha A.

AU - Hayes, Richard B.

AU - Henderson, Brian E.

AU - Hoffmeister, Michael

AU - Hopper, John L.

AU - Hudson, Thomas J.

AU - Hutter, Carolyn M.

AU - Jackson, Rebecca D.

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AU - Kantor, Elizabeth D.

AU - Kolonel, Laurence N.

AU - Küry, Sébastien

AU - Le Marchand, Loic

AU - Lemire, Mathieu

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Qu, Conghui

AU - Rosse, Stephanie A.

AU - Schoen, Robert E.

AU - Schumacher, Fred R.

AU - Seminara, Daniela

AU - Slattery, Martha L.

AU - Ulrich, Cornelia M.

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AU - Peters, Ulrike

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