TY - UNPB
T1 - Genomic analyses identify 15 susceptibility loci and reveal HDAC2 , SOX2-OT , and IGF2BP2 in a naturally-occurring canine model of gastric cancer
AU - Cook, Shawna R
AU - Hugen, Sanne
AU - Hayward, Jessica J
AU - Famula, Thomas R
AU - Belanger, Janelle M
AU - McNiel, Elizabeth
AU - Fieten, Hille
AU - Oberbauer, Anita M
AU - Leegwater, Peter A J
AU - Ostrander, Elaine A
AU - Mandigers, Paul J J
AU - Evans, Jacquelyn M
PY - 2024/8/16
Y1 - 2024/8/16
N2 - Gastric cancer (GC) is the fifth most common human cancer worldwide, but the genetic etiology is largely unknown. We performed a Bayesian genome-wide association study and selection analyses in a naturally-occurring canine model of GC, the Belgian Tervuren and Sheepdog breeds, to elucidate underlying genetic risk factors. We identified 15 loci with over 90% predictive accuracy for the GC phenotype. Variant filtering revealed germline putative regulatory variants for the
EPAS1 (
HIF2A ) and
PTEN genes and a coding variant in
CD101 . Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop GC. Across-breed analyses uncovered protective haplotypes under selection in Malinois at
SOX2-OT and
IGF2BP2 . Among Tervuren and Sheepdogs,
HDAC2 putative regulatory variants were present at comparatively high frequency and were associated with GC. Here, we describe a complex genetic architecture governing GC in a dog model, including genes such as
PDZRN3 , that have not been associated with human GC.
AB - Gastric cancer (GC) is the fifth most common human cancer worldwide, but the genetic etiology is largely unknown. We performed a Bayesian genome-wide association study and selection analyses in a naturally-occurring canine model of GC, the Belgian Tervuren and Sheepdog breeds, to elucidate underlying genetic risk factors. We identified 15 loci with over 90% predictive accuracy for the GC phenotype. Variant filtering revealed germline putative regulatory variants for the
EPAS1 (
HIF2A ) and
PTEN genes and a coding variant in
CD101 . Although closely related to Tervuren and Sheepdogs, Belgian Malinois rarely develop GC. Across-breed analyses uncovered protective haplotypes under selection in Malinois at
SOX2-OT and
IGF2BP2 . Among Tervuren and Sheepdogs,
HDAC2 putative regulatory variants were present at comparatively high frequency and were associated with GC. Here, we describe a complex genetic architecture governing GC in a dog model, including genes such as
PDZRN3 , that have not been associated with human GC.
U2 - 10.1101/2024.08.14.604426
DO - 10.1101/2024.08.14.604426
M3 - Preprint
C2 - 39372775
BT - Genomic analyses identify 15 susceptibility loci and reveal HDAC2 , SOX2-OT , and IGF2BP2 in a naturally-occurring canine model of gastric cancer
PB - bioRxiv
ER -
