Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan

Zoe Kemp, Luis Carvajal-Carmona, Sarah Spain, Ella Barclay, Margaret Gorman, Lynn Martin, Emma Jaeger, Neil Brooks, D. Timothy Bishop, Huw Thomas, Ian Tomlinson, Elli Papaemmanuil, Emily Webb, Gabrielle S. Sellick, Wendy Wood, Gareth Evans, Anneke Lucassen, Eamonn R. Maher, Richard S. Houlston

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10 204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P = 0.0003) at chromosomal region 3q21-q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD = 3.10, genome-wide P = 0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.

Original languageEnglish (US)
Pages (from-to)2903-2910
Number of pages8
JournalHuman Molecular Genetics
Volume15
Issue number19
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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