Exploring the role of alcohol in the causal chain between pancreatitis and arterial diseases: A Mendelian randomization study

BACKGROUND: This study was motivated by the increased prevalence of pancreatitis, along with the considerable morbidity and socioeconomic impact caused by its severe complications. It is essential to understand pancreatitis’ association with systemic arterial disease. METHODS: The Mendelian randomization (MR) method was used to analyze the single-nucleotide polymorphism data related to common arterial diseases in individuals with pancreatitis from the FinnGen and Genetic Consortium for Alcohol and Nicotine use databases. Causality was primarily evaluated using the inverse variance weighted method. In addition, multivariable MR (MVMR) analysis was performed to account for potential interference from alcohol-related phenotypes. Sensitivity analysis was conducted to validate the robustness of the results. RESULTS: This study examined the relationship between four types of pancreatitis (acute pancreatitis [AP], alcohol-induced acute pancreatitis [AAP], chronic pancreatitis [CP], and alcohol-induced CP [ACP]), as well as 17 different arterial diseases. Positive results were specifically found in vascular dementia, aneurysms, and isolated proteinuria. Initial univariable MR analysis indicated an increased risk of vascular dementia in individuals with CP and ACP, as well as a higher risk of vascular dementia (multiple infarctions) in those with all types of pancreatitis. Furthermore, individuals with all types of pancreatitis were also at a greater risk of developing some types of aneurysms. Cerebral aneurysms were associated with an increased risk of CP and ACP, while isolated proteinuria seemed to have a protective effect in individuals with all types of pancreatitis. Reverse MR analysis suggested a predominantly unidirectional causal relationship between pancreatitis and systemic arterial disease. Finally, MVMR analysis showed that there was no causal effect of pancreatitis on susceptibility to vascular dementia and vascular dementia (multiple infarctions) after adjusting for alcohol consumption. CONCLUSION: This study revealed a strong link between pancreatitis and cerebral aneurysms and other aneurysms, as well as a protective effect against isolated proteinuria. Reverse MR suggested a one-way causal relationship between pancreatitis and arterial disease. The multivariable analysis indicated that even without alcohol consumption, pancreatitis still had a strong direct causal effect on vascular diseases.