Allelic effects on <i>KLHL17</i> expression likely mediated by JunB/D underlie a PDAC GWAS signal at chr1p36.33.

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 (r²=0.93 in 1000G EUR samples, OR=1.23, P value=2.74x10^-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 th

SUBMITTER: Connelly KE 

PROVIDER: S-EPMC11451706 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature