{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:18:33Z","timestamp":1768565913681,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,16]]},"group-title":"Genetic and Genomic Medicine","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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\n                  <jats:sup>2<\/jats:sup>\n                  =0.93 in 1000G EUR samples, OR=1.23,\n                  <jats:italic>P<\/jats:italic>\n                  value=2.74\u00d710\n                  <jats:sup>\u22129<\/jats:sup>\n                  ) demonstrated allele-preferential gene regulatory activity\n                  <jats:italic>in vitro<\/jats:italic>\n                  and allele-preferential binding of JunB and JunD\n                  <jats:italic>in vitro<\/jats:italic>\n                  and\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Expression Quantitative Trait Locus (eQTL) analysis identified\n                  <jats:italic>KLHL17<\/jats:italic>\n                  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.\n                  <jats:italic>In silico<\/jats:italic>\n                  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.\n                <\/jats:p>","DOI":"10.1101\/2024.09.16.24313748","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T16:05:19Z","timestamp":1726761919000},"source":"Crossref","is-referenced-by-count":0,"title":["Allelic effects on\n                  <i>KLHL17<\/i>\n                  expression likely mediated by JunB\/D underlie a PDAC GWAS signal at chr1p36.33"],"prefix":"10.64898","author":[{"given":"Katelyn E.","family":"Connelly","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Hullin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehssan","family":"Abdolalizadeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daina","family":"Eiser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aidan","family":"O\u2019Brien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Collins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudipto","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Pancreatic Cancer Cohort Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Pancreatic Cancer Case-Control Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J.","family":"Chanock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachael Z.","family":"Stolzenberg-Solomon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2737-8399","authenticated-orcid":false,"given":"Alison P.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M.","family":"Wolpin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason 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