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Whilst common genetic variation in many non-coding genomic regulatory regions are known to impart risk of colorectal cancer (CRC), much of the heritability of CRC remains unexplained. To examine the role of recurrent coding sequence variation in CRC aetiology, we genotyped 12,638 CRCs cases and 29,045 controls from six European populations. Single-variant analysis identified a coding variant (rs3184504) in SH2B3 (12q24) associated with CRC risk (OR = 1.08, P = 3.9 × 10(-7)), and novel damaging coding variants in 3 genes previously tagged by GWAS efforts; rs16888728 (8q24) in UTP23 (OR = 1.15, P = 1.4 × 10(-7)); rs6580742 and rs12303082 (12q13) in FAM186A (OR = 1.11, P = 1.2 × 10(-7) and OR = 1.09, P = 7.4 × 10(-8)); rs1129406 (12q13) in ATF1 (OR = 1.11, P = 8.3 × 10(-9)), all reaching exome-wide significance levels. Gene based tests identified associations between CRC and PCDHGA genes (P 

Original publication

DOI

10.1038/srep16286

Type

Journal article

Journal

Scientific reports

Publication Date

11/2015

Volume

5

Addresses

Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, United Kingdom.

Keywords

Humans, Colorectal Neoplasms, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Proteins, Cadherins, Odds Ratio, Case-Control Studies, Gene Frequency, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Alleles, Activating Transcription Factor 1, Genetic Variation, Genome-Wide Association Study, Whites