Schmidt, Andreas W. and Kuehnapfel, Andreas and Kirsten, Holger and Grallert, Harald and Hellerbrand, Claus and Kiefer, Falk and Mann, Karl and Mueller, Sebastian and No, Markus M. and Peters, Annette and Ridinger, Monika and Frank, Josef and Rietschel, Marcella and Soranzo, Nicole and Soyka, Michael and Wodarz, Norbert and Malerba, Giovanni and Gambaro, Giovanni and Gieger, Christian and Scholz, Markus and Krug, Sebastian and Michl, Patrick and Ewers, Maren and Witt, Heiko and Laumen, Helmut and Rosendahl, Jonas (2022) Colocalization analysis of pancreas eQTLs with risk loci from alcoholic and novel non-alcoholic chronic pancreatitis GWAS suggests potential disease causing mechanisms. PANCREATOLOGY, 22 (4). pp. 449-456. ISSN 1424-3903, 1424-3911
Full text not available from this repository. (Request a copy)Abstract
Background: Previous genome-wide association studies (GWAS) identified genome-wide significant risk loci in chronic pancreatitis and investigated underlying disease causing mechanisms by simple overlaps with expression quantitative trait loci (eQTLs), a procedure which may often result in false positive conclusions. Methods: We conducted a GWAS in 584 non-alcoholic chronic pancreatitis (NACP) patients and 6040 healthy controls. Next, we applied Bayesian colocalization analysis of identified genome-wide significant risk loci from both, our recently published alcoholic chronic pancreatitis (ACP) and the novel NACP dataset, with pancreas eQTLs from the GTEx V8 European cohort to prioritize candidate causal genes and extracted credible sets of shared causal variants. Results: Variants at the CTRC (p = 1.22 x 10(-21)) and SPINKI (p = 6.59 x 10(-47)) risk loci reached genome-wide significance in NACP. CTRC risk variants colocalized with CTRC eQTLs in ACP (PP4 = 0.99, PP4/PP3 = 95.51) and NACP (PP4 = 0.99, PP4/PP3 = 95.46). For both diseases, the 95% credible set of shared causal variants consisted of rs497078 and rs545634. CLDN2 MORC4 risk variants colocalized with CLDN2 eQTLs in ACP (PP4 = 0.98, PP4/PP3 = 42.20) and NACP (PP4 = 0.67, PP4/PP3 = 7.18), probably driven by the shared causal variant rs12688220. Conclusions: A shared causal CTRC risk variant might unfold its pathogenic effect in ACP and NACP by reducing CTRC expression, while the CLDN2 MORC4 shared causal variant rs12688220 may modify ACP and NACP risk by increasing CLDN2 expression. (C) 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEREDITARY PANCREATITIS; GENE; VARIANTS; MUTATIONS; PRSS1-PRSS2; EXPRESSION; INHIBITOR; SECRETION; PACKAGE; Bayesian colocalization analysis; eQTL; GWAS; Chronic pancreatitis; GTEx |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 14:36 |
| Last Modified: | 12 Dec 2023 14:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58733 |
Actions (login required)
 |
View Item |
