Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33

COGENT Consortium, Richard S Houlston, Jeremy Cheadle, Sara E Dobbins, Albert Tenesa, Angela M Jones, Kimberley Howarth, Sarah L Spain, Peter Broderick, Enric Domingo, Susan Farrington, James Prendergast, Alan M Pittman, Evi Theodoratou, Christopher G Smith, Bianca Olver, Axel Walther, Rebecca A Barnetson, Michael Churchman, Emma E M JaegerSteven Penegar, Ella Barclay, Lynn Martin, Maggie Gorman, Rachel Mager, Elaine Johnstone, Rachel Midgley, Iina Niittymäki, Sari Tuupanen, James Colley, Shelley Idziaszczyk, Huw J W Thomas, Anneke M Lucassen, D Gareth R Evans, Eamonn R Maher, Timothy Maughan, Antigone Dimas, Emmanouil Dermitzakis, Jean-Baptiste Cazier, Lauri A Aaltonen, Paul Pharoah, David J Kerr, Luis G Carvajal-Carmona, Harry Campbell, Malcolm G Dunlop, Ian P M Tomlinson

Research output: Contribution to journalArticlepeer-review

Abstract

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10⁻¹⁰ and rs6687758, OR = 1.09, P = 2.27 × 10⁻⁹, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10⁻⁸), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10⁻¹⁰ and rs7136702, OR = 1.06, P = 4.02 × 10⁻⁸) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10⁻¹⁰). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.
Original languageEnglish
Pages (from-to)973-979
Number of pages7
JournalNature Genetics
Volume42
Issue number11
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 13
  • Chromosomes, Human, Pair 3
  • Colorectal Neoplasms
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Odds Ratio
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Risk Assessment

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