Page 65 - JCBP-3-3

Journal of Clinical and
Basic Psychosomatics Depression and chronic pancreatitis: MR study

A

B

Figure 3. Forest plot illustrating the causal effect of depression on chronic pancreatitis (A) and the association between chronic pancreatitis and depression (B).
Abbreviations: CI: Confidence interval; MR: Mendelian randomization; nSNP: Number of single-nucleotide polymorphisms; OR: Odds ratio.

loci. To investigate whether these shared SNPs have
downstream functional effects, we extracted expression
quantitative trait locus data for the SNPs from the GTEx
Portal (https://www.gtexportal.org), including data from
visceral and subcutaneous adipose tissue, pancreas, brain,
and other tissues. We found that rs9271510 is associated
with the expression of several genes in the pancreas,
including major histocompatibility complex, class II, DQ
alpha 1 (HLA-DQA1), major histocompatibility complex,
class II, DQ beta 2, and major histocompatibility complex,
class II, DR beta 6. In addition, we identified that the gene
corresponding to the shared SNP is HLA-DQA1.
4. Discussion

In this study, we applied two-step MR and two-sample
Figure 4. Forest plot to visualize the association between depression and MR analyses to investigate the causal relationship between
chronic pancreatitis after adjusting for five other exposures depression and CP using summary data from GWAS. The
Abbreviations: ADPW: Alcoholic drinks per week; BMI: Body mass MR-IVW forward analysis provided evidence of a genetic
index; CI: Confidence interval; MDD: Major depression disorder; vulnerability to depression that is linked to an increased risk
OR: Odds ratio; SI: Smoking initiation; TG: Triglycerides; T2DM: Type 2
diabetes mellitus. of CP. In contrast, genetic liability to CP was not associated
with depression in the reverse MR-IVW analysis. Two-
step MR analyses indicated that the association between
3.3. Genetic loci of CP and depression
depression and CP was mediated by triglycerides, smoking
To explore whether CP and depression share common initiation, and type 2 diabetes. A previous MR study has
genetic loci, we first obtained GWAS summary data shown that smoking initiation and higher triglyceride levels
from the FinnGen database. Given that no shared SNPs are associated with an increased risk of CP. This study
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were identified with p-threshold of <5 × 10 , we relaxed also provides evidence supporting the causal association
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p-threshold to <2 × 10 and identified three shared between type 2 diabetes, smoking, and the risk of acute
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Volume 3 Issue 3 (2025) 59 doi: 10.36922/jcbp.5892