{"doi":"10.1101/2024.08.14.604426","title":"Genomic analyses identify 15 susceptibility loci and reveal <i>HDAC2</i> , <i>SOX2-OT</i> , and <i>IGF2BP2</i> in a naturally-occurring canine model of gastric cancer","abstract":"SUMMARY 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":491644,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9146,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1337203,"name":"Sanne Hugen","orcid":"0009-0006-3864-8680","position":1,"is_corresponding":false},{"id":766890,"name":"Jessica J. Hayward","orcid":"0000-0001-6213-5013","position":2,"is_corresponding":false},{"id":743167,"name":"Thomas R. Famula","orcid":"0000-0002-3139-9849","position":3,"is_corresponding":false},{"id":788638,"name":"Janelle M. Belanger","orcid":"0000-0002-3703-260X","position":4,"is_corresponding":false},{"id":1182310,"name":"Elizabeth A. McNiel","orcid":"0000-0003-4549-4828","position":5,"is_corresponding":false},{"id":510037,"name":"Hille Fieten","orcid":"0000-0002-0562-6964","position":6,"is_corresponding":false},{"id":788637,"name":"Anita M. Oberbauer","orcid":"0000-0002-3945-2851","position":7,"is_corresponding":false},{"id":414483,"name":"Peter A. J. Leegwater","orcid":"0000-0002-4100-015X","position":8,"is_corresponding":false},{"id":98041,"name":"Elaine A. Ostrander","orcid":"0000-0001-6075-9738","position":9,"is_corresponding":false},{"id":414482,"name":"Paul J. J. Mandigers","orcid":"0000-0003-2547-6673","position":10,"is_corresponding":false},{"id":711219,"name":"Jacquelyn M. Evans","orcid":"0000-0003-1272-0059","position":11,"is_corresponding":false},{"id":403843,"name":"Shawna R. Cook","orcid":"0000-0001-7967-9607","position":0,"is_corresponding":true}],"reference_count":158,"raw_metadata":null,"created_at":"2026-07-19T02:08:45.247225Z","pmid":"39372775","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}