A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer.

ABSTRACT: Genome-wide association studies (GWASs) have discovered 20 risk loci in the human genome where germline variants associate with risk of pancreatic ductal adenocarcinoma (PDAC) in populations of European ancestry. Here, we fine-mapped one such locus on chr16q23.1 (rs72802365, p = 2.51 × 10^-17, OR = 1.36, 95% CI = 1.31-1.40) and identified colocalization (PP = 0.87) with aberrant exon 5-7 CTRB2 splicing in pancreatic tissues (p_GTEx = 1.40 × 10^-69, β_GTEx = 1.99; p_LTG = 1.02 × 10^-30, β_LTG = 1.99). Imputation of a 584 bp structural variant overlapping exon 6 of CTRB2 into the GWAS datasets resulted in a highly significant association with pancreatic cancer risk (p = 2.83 × 10^-16, OR = 1.36, 95% CI = 1.31-1.4

SUBMITTER: Jermusyk A 

PROVIDER: S-EPMC8546220 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature