Antihypertensive drug targets and pancreatitis reporting signals: An integrative mendelian randomization and FAERS pharmacovigilance study
4 affiliations
- 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- 2School of Future Technology, Xi’an Jiaotong University, Xi’an, Shaanxi, China
- 3Department of Neonatology, The Affiliated Hospital of Qingdao University, Qingdao, China
- 4Department of Thoracic Surgery, Peking University People’s Hospital, Beijing, China
Abstract
Objective: To investigate whether genetically proxied antihypertensive drug targets are associated with pancreatic exocrine diseases and whether corresponding antihypertensive agents show pancreatitis-related pharmacovigilance signals.
Methods: This integrative genetic epidemiology and pharmacovigilance study combined linkage disequilibrium score regression, two-sample Mendelian randomization, summary-data-based Mendelian randomization, Bayesian colocalization, and FAERS disproportionality analysis. Publicly available GWAS summary statistics were derived predominantly from European-ancestry participants, and whole-blood cis-eQTLs were used to genetically proxy antihypertensive drug-target expression. FAERS reports submitted from 2004 to 2023 were analyzed for pancreatitis-related reporting signals.
Results: Among 21 antihypertensive drug targets, ADRB2, CACNA1I, JUN, NR3C2, and SLC12A4 showed nominal associations with pancreatic outcomes; however, none remained significant after Bonferroni correction. Absolute PP.H4 values did not support robust colocalization. Although several target-outcome pairs had high conditional PP.H4 values, these findings provide only relative support for H4 over H3 when both traits are assumed to have regional association signals. Several antihypertensive agents also generated pancreatitis-related reporting signals in FAERS; these signals do not quantify incidence or establish causality.
Conclusions: The findings are exploratory and prioritize selected antihypertensive targets and drugs for replication and mechanistic study. They do not establish causal effects, robust colocalization, or an increased incidence of pancreatitis.
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BibTeX
@article{li2026antihypertensive,
title = {{Antihypertensive drug targets and pancreatitis reporting signals: An integrative mendelian randomization and FAERS pharmacovigilance study}},
author = {Chang-Lei Li and Si-Han Wang and Zhi-Yuan Yao and Xiao-Tong Cui and Zu-Sen Wang},
journal = {Science Progress},
year = {2026},
month = sep,
doi = {10.1177/00368504261491552},
url = {https://doi.org/10.1177/00368504261491552},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Antihypertensive drug targets and pancreatitis reporting signals: An integrative mendelian randomization and FAERS pharmacovigilance study
AU - Chang-Lei Li
AU - Si-Han Wang
AU - Zhi-Yuan Yao
AU - Xiao-Tong Cui
AU - Zu-Sen Wang
PY - 2026
DA - 2026/09/21
JO - Science Progress
DO - 10.1177/00368504261491552
UR - https://doi.org/10.1177/00368504261491552
AB - Objective: To investigate whether genetically proxied antihypertensive drug targets are associated with pancreatic exocrine diseases and whether corresponding antihypertensive agents show pancreatitis-related pharmacovigilance signals. Methods: This integrative genetic epidemiology and pharmacovigilance study combined linkage disequilibrium score regression, two-sample Mendelian randomization, summary-data-based Mendelian randomization, Bayesian colocalization, and FAERS disproportionality analysis. Publicly available GWAS summary statistics were derived predominantly from European-ancestry participants, and whole-blood cis-eQTLs were used to genetically proxy antihypertensive drug-target expression. FAERS reports submitted from 2004 to 2023 were analyzed for pancreatitis-related reporting signals. Results: Among 21 antihypertensive drug targets, ADRB2, CACNA1I, JUN, NR3C2, and SLC12A4 showed nominal associations with pancreatic outcomes; however, none remained significant after Bonferroni correction. Absolute PP.H4 values did not support robust colocalization. Although several target-outcome pairs had high conditional PP.H4 values, these findings provide only relative support for H4 over H3 when both traits are assumed to have regional association signals. Several antihypertensive agents also generated pancreatitis-related reporting signals in FAERS; these signals do not quantify incidence or establish causality. Conclusions: The findings are exploratory and prioritize selected antihypertensive targets and drugs for replication and mechanistic study. They do not establish causal effects, robust colocalization, or an increased incidence of pancreatitis.
SN - 0036-8504
SN - 2047-7163
ER -