Title: Genetic evidence causally linking gastroesophageal reflux disease to cholecystitis#A two-
sample Mendelian randomization study
Version: 1 Date: 23 Jul 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors performed a critical and massive revision according to
the revisors’ requests. The revised manuscript has been largely revised when not completely
rewritten. The current version is much clearer and more comprehensive. However, still
elucidates the limited analyses performed in the study and inconclusive.
REQUESTED REVISIONS:
The study is empowered by an extremely large cohort, but with very limited analyses and SNP
correlation.
Minor details and corrections still required before publication:
The statistical analysis section in M&M requires the authors to specify a minimal level of
significance and description of how results have been reported and represented.
In the Results section: Section 3.1, third line: expressions like “indicating that none of the SNPs
were weak IVs” should be revised and reconsidered. Weak expression has no meaning in such
a context
Despite how much we appreciate the authors’ intention and will to improve the study by
including additional, required, data, the Additional file 1-2 is not self-explanatory, nor is adding
much in the actual form. We would encourage the authors to further analyze and properly
represent such information on each SNP.
In the discussion, the authors correctly reported the advantages of using the MR approach.
However, critical analysis and description, including limitations and further investigation
required to support conclusions would be appropriate.
We found nothing concerning pathophysiological mechanism(s) or current knowledge on
gastroesophageal reflux and cholecystitis.
We read several speculative affirmations and hypotheses in the discussion, in relation to The
motor function of the gastroesophageal and biliary tract systems. We would suggest smoothing
such affirmations up, a little bit. Or, even better, include additional results or literature reports
in support of such a potential mechanism.
ADDITIONAL REQUESTS/SUGGESTIONS:
Based on limited results, all the limitations (acknowledged correctly by the authors), and still
inconclusive conclusions, we would suggest the authors to consider a short report rather than
a full original article
Title: Genetic evidence causally linking gastroesophageal reflux disease to cholecystitis#A two-
sample Mendelian randomization study
Version: 1 Date: 23 Jul 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors performed a critical and massive revision according to
the revisors’ requests. The revised manuscript has been largely revised when not completely
rewritten. The current version is much clearer and more comprehensive. However, still
elucidates the limited analyses performed in the study and inconclusive.
REQUESTED REVISIONS:
The study is empowered by an extremely large cohort, but with very limited analyses and SNP
correlation.
Minor details and corrections still required before publication:
The statistical analysis section in M&M requires the authors to specify a minimal level of
significance and description of how results have been reported and represented.
In the Results section: Section 3.1, third line: expressions like “indicating that none of the SNPs
were weak IVs” should be revised and reconsidered. Weak expression has no meaning in such
a context
Despite how much we appreciate the authors’ intention and will to improve the study by
including additional, required, data, the Additional file 1-2 is not self-explanatory, nor is adding
much in the actual form. We would encourage the authors to further analyze and properly
represent such information on each SNP.
In the discussion, the authors correctly reported the advantages of using the MR approach.
However, critical analysis and description, including limitations and further investigation
required to support conclusions would be appropriate.
We found nothing concerning pathophysiological mechanism(s) or current knowledge on
gastroesophageal reflux and cholecystitis.
We read several speculative affirmations and hypotheses in the discussion, in relation to The
motor function of the gastroesophageal and biliary tract systems. We would suggest smoothing
such affirmations up, a little bit. Or, even better, include additional results or literature reports
in support of such a potential mechanism.
ADDITIONAL REQUESTS/SUGGESTIONS:
Based on limited results, all the limitations (acknowledged correctly by the authors), and still
inconclusive conclusions, we would suggest the authors to consider a short report rather than
a full original article
Please review this paper.
user
Title: Genetic evidence causally linking gastroesophageal reflux disease to cholecystitis#A two-
sample Mendelian randomization study
Version: 1 Date: 23 Jul 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses one or several
testable research questions? (Brief or other article types: is there a clear objective?)
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are minor issues
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are major issues
OVERALL MANUSCRIPT POTENTIAL - Has the author addressed your concerns sufficiently
for you to now recommend the work as a technically sound contribution? If not, can further
revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors performed a critical and massive revision according to
the revisors’ requests. The revised manuscript has been largely revised when not completely
rewritten. The current version is much clearer and more comprehensive. However, still
elucidates the limited analyses performed in the study and inconclusive.
REQUESTED REVISIONS:
The study is empowered by an extremely large cohort, but with very limited analyses and SNP
correlation.
Minor details and corrections still required before publication:
The statistical analysis section in M&M requires the authors to specify a minimal level of
significance and description of how results have been reported and represented.
In the Results section: Section 3.1, third line: expressions like “indicating that none of the SNPs
were weak IVs” should be revised and reconsidered. Weak expression has no meaning in such
a context
Despite how much we appreciate the authors’ intention and will to improve the study by
including additional, required, data, the Additional file 1-2 is not self-explanatory, nor is adding
much in the actual form. We would encourage the authors to further analyze and properly
represent such information on each SNP.
In the discussion, the authors correctly reported the advantages of using the MR approach.
However, critical analysis and description, including limitations and further investigation
required to support conclusions would be appropriate.
We found nothing concerning pathophysiological mechanism(s) or current knowledge on
gastroesophageal reflux and cholecystitis.
We read several speculative affirmations and hypotheses in the discussion, in relation to The
motor function of the gastroesophageal and biliary tract systems. We would suggest smoothing
such affirmations up, a little bit. Or, even better, include additional results or literature reports
in support of such a potential mechanism.
ADDITIONAL REQUESTS/SUGGESTIONS:
Based on limited results, all the limitations (acknowledged correctly by the authors), and still
inconclusive conclusions, we would suggest the authors to consider a short report rather than
a full original article
assistant