DOI: 10.5061/dryad.pg4f4qrzs
title: Data from: Genomic analyses identify 15 susceptibility loci and reveal HDAC2, SOX2-OT, and IGF2BP2 in a naturally-occurring canine model of gastric cancer

description: Gastric cancer ranks as the fifth most common human cancer worldwide and
 has a poor survival rate and limited treatment options. Despite the high
 prevalence and mortality rate, the genetic etiology is largely unknown. In
 dogs, a clinically and histologically similar disease disproportionately
 affects two breeds, the Belgian Tervuren and Belgian Sheepdog, who develop
 the intestinal and diffuse tumor subtypes observed in humans. We performed
 a Bayesian genome-wide association study and selection analyses in this
 naturally-occurring canine model to elucidate underlying genetic risk
 factors for gastric cancer and identified 15 associated loci. Variant
 filtering revealed germline putative regulatory variants for the EPAS1
 (HIF2A) and PTEN genes and a coding variant in CD101. Two loci are
 overrepresented among cases of intestinal tumor subtype. Although closely
 related to Tervuren and Sheepdogs, Belgian Malinois rarely develop gastric
 cancer. Across-breed analyses uncovered haplotypes enriched in Malinois at
 SOX2-OT and IGF2BP2 that are at significantly higher frequency among GWAS
 controls. Among Tervuren and Sheepdogs, HDAC2 putative regulatory variants
 were present at comparatively high frequency and were associated with risk
 of gastric cancer. Here, we describe a complex genetic architecture
 governing gastric cancer in a dog model, including genes such as PDZRN3
 and KLHL29, that have not been associated with human gastric cancer.
description: # Data from: Genomic analyses identify 15 susceptibility loci and reveal
 HDAC2, SOX2-OT, and IGF2BP2 in a naturally-occurring canine model of
 gastric cancer
 [https://doi.org/10.5061/dryad.pg4f4qrzs](https://doi.org/10.5061/dryad.pg4f4qrzs) ## Description of the data and file structure Manuscript entitled: "Genomic analyses identify 15 susceptibility loci and reveal HDAC2, SOX2-OT, and IGF2BP2 in a naturally-occurring canine model of gastric cancer" Authors: Shawna R. Cook, Sanne Hugen, Jessica J. Hayward, Thomas R. Famula, Janelle M. Belanger, Elizabeth McNiel, Hille Fieten, Anita M. Oberbauer, Peter A.J. Leegwater, Elaine A. Ostrander, Paul J.J. Mandigers, Jacquelyn M. Evans This fileset includes: 1\. Binary PLINK files containing genotype data of 363 Belgian shepherd dogs run on the 173k Illumina CanineHD BeadChip array with positions reported in CanFam3.1 reference. 173k_prephased_highcall.fam 173k_prephased_highcall.bim 173k_prephased_highcall.bed 2\. Binary PLINK files containing genotype data of 365 Belgian shepherd dogs run on Embark’s custom high-density Illumina 220k SNP array with positions reported in CanFam3.1 reference. 220k_prephased_highcall.fam 220k_prephased_highcall.bim 220k_prephased_highcall.bed 3\. Binary PLINK files containing genotype data of 184 Belgian shepherd dogs run on the Affymetrix Axiom Canine HD Array with positions reported in CanFam3.1 reference. 670k_prephased_highcall.fam 670k_prephased_highcall.bim 670k_prephased_highcall.bed 4\. Binary PLINK files containing imputed genotype data of 870 Belgian shepherd dogs. Dogs genotyped on multiple arrays have the same ID with "_173k", "_220k", or "_670k" appended to denote the SNP array of origin. Imputed.fam Imputed.bim Imputed.bed