Title: Inflammatory bowel disease increases the risk of pancreatitis: A two-sample bidirectional
mendelian randomization analysis
Version: 1 Date: 13 Jul 2024
Reviewer's report:
The present study aimed to explore the potential causal relationship between inflammatory
bowel disease (IBD) and pancreatitis through Mendelian randomization (MR). Utilizing
genome-wide association study (GWAS) data from European individuals, the analysis revealed
that a genetic predisposition to pancreatitis is associated with an increased risk of IBD.
Specifically, ulcerative colitis (UC) was found to elevate the risk of acute pancreatitis, while
Crohn’s disease (CD) was linked to a higher risk of chronic pancreatitis. These findings suggest
a differential impact of IBD subtypes on pancreatitis risk.  Before the manuscript is officially
published, I believe some revisions are necessary.
In Table 1, the data sources for pancreatitis should be from FinnGen rather than IIBDGC.
Currently, FinnGen has updated GWAS data for pancreatitis with a larger number of cases. The
authors could consider utilizing these updated data to increase statistical power, as the existing
p-values are not robust enough. The pancreatitis GWAS data in this article only come from the
FinnGen cohort; perhaps the authors could use the UK Biobank (UKB) pancreatitis GWAS data
for validation.
In the methodology, the authors should clearly specify how the F-statistic was calculated,
including the overall F-statistic and the F-statistic for each instrumental variable, as well as R^2.
Refer to this article (PMID: 36904153). I suggest showing the overall F-statistic in Figure 3
instead of the maximum and minimum F-statistic.
Could the authors perform a reverse MR analysis to investigate whether there is a causal effect of
pancreatitis on IBD? Given that there are fewer instrumental variables for pancreatitis GWAS,
the authors could use a more lenient threshold (1E-5).
Title: Inflammatory bowel disease increases the risk of pancreatitis: A two-sample bidirectional
mendelian randomization analysis
Version: 1 Date: 13 Jul 2024
Reviewer's report:
The present study aimed to explore the potential causal relationship between inflammatory
bowel disease (IBD) and pancreatitis through Mendelian randomization (MR). Utilizing
genome-wide association study (GWAS) data from European individuals, the analysis revealed
that a genetic predisposition to pancreatitis is associated with an increased risk of IBD.
Specifically, ulcerative colitis (UC) was found to elevate the risk of acute pancreatitis, while
Crohn’s disease (CD) was linked to a higher risk of chronic pancreatitis. These findings suggest
a differential impact of IBD subtypes on pancreatitis risk.  Before the manuscript is officially
published, I believe some revisions are necessary.
In Table 1, the data sources for pancreatitis should be from FinnGen rather than IIBDGC.
Currently, FinnGen has updated GWAS data for pancreatitis with a larger number of cases. The
authors could consider utilizing these updated data to increase statistical power, as the existing
p-values are not robust enough. The pancreatitis GWAS data in this article only come from the
FinnGen cohort; perhaps the authors could use the UK Biobank (UKB) pancreatitis GWAS data
for validation.
In the methodology, the authors should clearly specify how the F-statistic was calculated,
including the overall F-statistic and the F-statistic for each instrumental variable, as well as R^2.
Refer to this article (PMID: 36904153). I suggest showing the overall F-statistic in Figure 3
instead of the maximum and minimum F-statistic.
Could the authors perform a reverse MR analysis to investigate whether there is a causal effect of
pancreatitis on IBD? Given that there are fewer instrumental variables for pancreatitis GWAS,
the authors could use a more lenient threshold (1E-5).
Please review this paper.
user
Title: Inflammatory bowel disease increases the risk of pancreatitis: A two-sample bidirectional
mendelian randomization analysis
Version: 1 Date: 13 Jul 2024
Reviewer's report:
The present study aimed to explore the potential causal relationship between inflammatory
bowel disease (IBD) and pancreatitis through Mendelian randomization (MR). Utilizing
genome-wide association study (GWAS) data from European individuals, the analysis revealed
that a genetic predisposition to pancreatitis is associated with an increased risk of IBD.
Specifically, ulcerative colitis (UC) was found to elevate the risk of acute pancreatitis, while
Crohn’s disease (CD) was linked to a higher risk of chronic pancreatitis. These findings suggest
a differential impact of IBD subtypes on pancreatitis risk.  Before the manuscript is officially
published, I believe some revisions are necessary.
In Table 1, the data sources for pancreatitis should be from FinnGen rather than IIBDGC.
Currently, FinnGen has updated GWAS data for pancreatitis with a larger number of cases. The
authors could consider utilizing these updated data to increase statistical power, as the existing
p-values are not robust enough. The pancreatitis GWAS data in this article only come from the
FinnGen cohort; perhaps the authors could use the UK Biobank (UKB) pancreatitis GWAS data
for validation.
In the methodology, the authors should clearly specify how the F-statistic was calculated,
including the overall F-statistic and the F-statistic for each instrumental variable, as well as R^2.
Refer to this article (PMID: 36904153). I suggest showing the overall F-statistic in Figure 3
instead of the maximum and minimum F-statistic.
Could the authors perform a reverse MR analysis to investigate whether there is a causal effect of
pancreatitis on IBD? Given that there are fewer instrumental variables for pancreatitis GWAS,
the authors could use a more lenient threshold (1E-5).
assistant