Genetic liability for acute and chronic pancreatitis shows strong correlation and identifies potential drug targetsGenetic links and proteins show shared roots of pancreatitis

medRxiv Published September 19, 2026 Study authors: Khodursky, S.; Judy, R.; Abramowitz, S.; Levin, M. G.; Damrauer, S. M. DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Note that strong genetic correlation (rg=0.89) and specific drug-target genes identify potential pathways for pancreatitis.

This meta-analysis investigates the genetic architecture of acute pancreatitis (AP) and chronic pancreatitis (CP) using a large multi-population sample. The study integrates genome-wide association studies (GWAS) with Mendelian randomization (MR) to explore the roles of plasma proteins and drug-target expression in disease liability.

Key findings include the identification of 16 genome-wide significant loci for AP and 14 for CP. A strong genetic correlation of rg=0.89 was found between AP and CP, although 44 regions showed lower correlation, including a specific region on chromosome 18 containing BCL2. Proteome-wide MR identified 15 proteins associated with AP and 6 proteins associated with CP. Furthermore, drug-target MR identified 38 target genes associated with AP and 45 target genes associated with CP.

The study also noted that non-O blood type is modestly but significantly associated with both conditions. While the study identifies tractable therapeutic targets, such as DRD2 for AP and BCHE for CP, these are potential targets rather than proven treatments. The results provide a framework for understanding the shared genetic basis of these conditions and identifying pathways for future pharmacological intervention.

How this fits prior evidence

This meta-analysis addresses a gap in understanding the underlying genetic and molecular drivers of pancreatitis. While prior evidence has identified specific risk factors like tamoxifen-induced hypertriglyceridemia and the presence of a fatty pancreas, this study provides a broader genomic landscape. It identifies specific genetic loci and potential drug targets, expanding the scope from clinical risk factors to molecular targets for AP and CP.

Living with pancreatitis can be a grueling experience, whether it is a sudden, painful flare-up or a long-term, chronic condition. Scientists wanted to know if these two forms of the disease share the same underlying causes. By looking at the genetic makeup of over 23,000 people with acute pancreatitis and over 9,000 people with chronic pancreatitis, they found a very strong link between the two conditions at the genetic level.

The study identified specific genetic locations and proteins in the blood that are linked to both types of the disease. For example, they found 16 genetic locations for acute pancreatitis and 14 for chronic. They also found that certain proteins and genes, such as DRD2 and BCHE, might be involved in the disease process. These findings suggest that the two conditions are more closely related than previously known.

While these results are promising, it is important to remember that this research identifies potential targets for future medicine rather than immediate treatments. The study also noted that having a non-O blood type was linked to both conditions. These findings provide a roadmap for researchers to develop more specific ways to treat the underlying causes of pancreatitis.

What this means for you:

Acute and chronic pancreatitis share strong genetic and protein links, identifying new targets for future treatment.

Common questions

Are acute and chronic pancreatitis related?

Yes, the study found a very strong genetic correlation between acute and chronic pancreatitis. Researchers found that the two conditions are linked at the genome-wide level, meaning they share many of the same underlying genetic markers.

What specific proteins or genes were linked to the condition?

The study identified 15 proteins associated with acute pancreatitis and 6 proteins associated with chronic pancreatitis. It also identified 38 target genes for acute pancreatitis and 45 target genes for chronic pancreatitis, including specific targets like DRD2 and BCHE.

Does blood type affect the risk of pancreatitis?

The study found that having a non-O blood type was modestly but significantly associated with both acute and chronic pancreatitis. This finding serves as a marker for how certain factors might influence the risk of developing the condition.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedSep 2026

View Original Abstract ↓

Acute (AP) and chronic (CP) pancreatitis are major causes of gastrointestinal morbidity. However, the genetic architectures of AP and CP remain incompletely defined, as does the degree to which the two conditions share a common genetic basis. Here we report a multi-population GWAS meta-analysis of both AP and CP across five biobanks, comprising 23,292 individuals with and 1,748,420 individuals without AP across five populations and 9,866 individuals with and 1,627,720 individuals without CP across three populations. We identified 16 and 14 genome-wide significant loci for AP and CP, respectively. Combining nearest-gene assignment, fine-mapping, MAGMA, and colocalization with pancreatic eQTLs, we prioritized 7 genes for AP and 5 genes for CP using two or more approaches, including three previously unreported candidates: TM4SF4 and TCIM for AP, and FFAR4 for CP. We demonstrated that AP and CP are strongly correlated at the genome-wide level (rg=0.89); however, we identified 44 regions with significantly lower correlations, including a region on chromosome 18 containing BCL2 with a negative local correlation. Plasma proteome-wide Mendelian randomization (MR) found 15 proteins whose genetically predicted plasma levels were associated with AP and 6 associated with CP, including ABO, whose measured levels likely proxy non-O blood type. Consistent with this, we found that non-O blood type was modestly but significantly associated with both AP and CP in an analysis of electronic health records from over 650,000 individuals. Finally, drug-target MR identified 38 and 45 target genes whose genetically predicted expression levels were associated with genetic liability for AP and CP, respectively. Among these, DRD2 and BCHE (for AP and CP, respectively) were also supported by colocalization analysis. Overall, these results expand the known genetic architecture of pancreatitis and identify tractable therapeutic targets.

Genetic liability for acute and chronic pancreatitis shows strong correlation and identifies potential drug targetsGenetic links and proteins show shared roots of pancreatitis

How this fits prior evidence

Common questions

Study Details

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Genetic liability for acute and chronic pancreatitis shows strong correlation and identifies potential drug targetsGenetic links and proteins show shared roots of pancreatitis

How this fits prior evidence

Common questions

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Study Details

TLR4 Asp299Gly polymorphism associated with increased infection susceptibility (OR 2.05) and mortality (HR 1.78)

Genetic variations linked to higher risk of severe infections

Clinical research that matters. Delivered to your inbox.

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