Proteome-Wide Mendelian Randomization Identifies Causal Links Between Blood Proteins and Acute Pancreatitis.
Acute Pancreatitis
Genetics
Mendelian Randomization and Therapeutic Targets
Proteome
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
15
09
2022
revised:
13
01
2023
accepted:
20
01
2023
medline:
25
4
2023
pubmed:
4
2
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
Acute pancreatitis (AP) is a complex disease and the leading cause of gastrointestinal disease-related hospital admissions. Few therapeutic options exist for AP prevention. Blood proteins with causal evidence may represent promising drug targets, but few have been causally linked with AP. Our objective was to identify blood proteins linked with AP by combining genome-wide association meta-analysis and proteome-wide Mendelian randomization (MR) studies. We performed a genome-wide association meta-analysis totalling 10,630 patients with AP and 844,679 controls and a series of inverse-variance weighted MR analyses using cis-acting variants on 4719 blood proteins from the deCODE study (N = 35,559) and 4979 blood proteins from the Fenland study (N = 10,708). The meta-analysis identified genome-wide significant variants (P <5 × 10 This large genome-wide association study meta-analysis for AP identified new variants linked with AP as well as several blood proteins that may be causally associated with AP. This study provides new information on the genetic architecture of this disease and identified pathways related to AP, which may be further explored as possible therapeutic targets for AP.
Sections du résumé
BACKGROUND & AIMS
Acute pancreatitis (AP) is a complex disease and the leading cause of gastrointestinal disease-related hospital admissions. Few therapeutic options exist for AP prevention. Blood proteins with causal evidence may represent promising drug targets, but few have been causally linked with AP. Our objective was to identify blood proteins linked with AP by combining genome-wide association meta-analysis and proteome-wide Mendelian randomization (MR) studies.
METHODS
We performed a genome-wide association meta-analysis totalling 10,630 patients with AP and 844,679 controls and a series of inverse-variance weighted MR analyses using cis-acting variants on 4719 blood proteins from the deCODE study (N = 35,559) and 4979 blood proteins from the Fenland study (N = 10,708).
RESULTS
The meta-analysis identified genome-wide significant variants (P <5 × 10
CONCLUSIONS
This large genome-wide association study meta-analysis for AP identified new variants linked with AP as well as several blood proteins that may be causally associated with AP. This study provides new information on the genetic architecture of this disease and identified pathways related to AP, which may be further explored as possible therapeutic targets for AP.
Identifiants
pubmed: 36736436
pii: S0016-5085(23)00100-2
doi: 10.1053/j.gastro.2023.01.028
pii:
doi:
Substances chimiques
Proteome
0
Blood Proteins
0
PRSS2 protein, human
103964-84-7
Trypsin
EC 3.4.21.4
Trypsinogen
9002-08-8
SPINK1 protein, human
0
Trypsin Inhibitor, Kazal Pancreatic
50936-63-5
MORC4 protein, human
0
Nuclear Proteins
0
Types de publication
Meta-Analysis
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
953-965.e3Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.