{"doi":"10.1101/2024.09.16.24313748","title":"Allelic effects on <i>KLHL17</i> expression likely mediated by JunB/D underlie a PDAC GWAS signal at chr1p36.33","abstract":"Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the U.S. Both rare and common germline variants contribute to PDAC risk. Here, we fine-map and functionally characterize a common PDAC risk signal at 1p36.33 (tagged by rs13303010) identified through a genome wide association study (GWAS). One of the fine-mapped SNPs, rs13303160 (r 2 =0.93 in 1000G EUR samples, OR=1.23, P value=2.74×10 −9 ) demonstrated allele-preferential gene regulatory activity in vitro and allele-preferential binding of JunB and JunD in vitro and in vivo . Expression Quantitative Trait Locus (eQTL) analysis identified KLHL17 as a likely target gene underlying the signal. Proteomic analysis identified KLHL17 as a member of the Cullin-E3 ubiquitin ligase complex in PDAC-derived cells. In silico differential gene expression analysis of the GTExv8 pancreas data suggested an association between lower KLHL17 (risk associated) and pro-inflammatory pathways. We hypothesize that KLHL17 may mitigate inflammation by recruiting pro-inflammatory proteins for ubiquitination and degradation thereby influencing PDAC risk.","journal":"medRxiv","year":2024,"id":503454,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"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":1353329,"name":"Katherine Hullin","orcid":"0000-0003-2550-6860","position":1,"is_corresponding":false},{"id":692935,"name":"Ehssan Abdolalizadeh","orcid":null,"position":2,"is_corresponding":false},{"id":319490,"name":"Jun Zhong","orcid":null,"position":3,"is_corresponding":false},{"id":692936,"name":"Daina Eiser","orcid":null,"position":4,"is_corresponding":false},{"id":692025,"name":"Aidan O’Brien","orcid":"0000-0003-2188-4223","position":5,"is_corresponding":false},{"id":692027,"name":"Irene Collins","orcid":"0000-0001-5434-4659","position":6,"is_corresponding":false},{"id":276004,"name":"Sudipto Das","orcid":"0009-0000-8325-0088","position":7,"is_corresponding":false},{"id":1033981,"name":"Gerard Duncan","orcid":null,"position":8,"is_corresponding":false},{"id":6431,"name":"Stephen J. Chanock","orcid":"0000-0002-2324-3393","position":9,"is_corresponding":false},{"id":302477,"name":"Rachael Z. Stolzenberg‐Solomon","orcid":"0000-0003-3698-7006","position":10,"is_corresponding":false},{"id":109497,"name":"Alison P. Klein","orcid":"0000-0003-2737-8399","position":11,"is_corresponding":false},{"id":56410,"name":"Brian M. Wolpin","orcid":"0000-0002-0455-1032","position":12,"is_corresponding":false},{"id":692026,"name":"Jason W. Hoskins","orcid":"0000-0001-6944-1996","position":13,"is_corresponding":false},{"id":276014,"name":"Þorkell Andrésson","orcid":"0000-0002-9545-2450","position":14,"is_corresponding":false},{"id":404341,"name":"Jill P. Smith","orcid":"0000-0002-0835-4802","position":15,"is_corresponding":false},{"id":264809,"name":"Laufey T. Ámundadóttir","orcid":"0000-0003-1859-8971","position":16,"is_corresponding":false},{"id":692023,"name":"Katelyn E. Connelly","orcid":"0000-0002-1693-5519","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:10:31.826282Z","pmid":"39371158","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":[]}