Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 2 Date: 04 Apr 2025
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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?
Yes - the author's interpretation is reasonable
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?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have provided a thoughtful, detailed, and
comprehensive revision in response to the reviewer’s comments. Specifically, the authors
have significantly strengthened the manuscript by explicitly addressing key methodological
limitations inherent in Mendelian Randomization (MR), such as residual pleiotropy and
population specificity. The adjustments made in the "Conclusion" section clearly articulate these
potential limitations and provide appropriate recommendations for future research directions.
Additionally, the revised manuscript demonstrates enhanced clarity in discussing specific lipid
species (LPC 18:1 and LPC 20:4), differentiating their clinical implications for Ulcerative Colitis
(UC) and Crohn’s Disease (CD).
Although minor issues remain, including residual concerns about potential pleiotropy indicated
by some significant MR-Egger intercept tests, the authors acknowledged these issues
transparently, suggesting future research directions that could comprehensively address these
concerns.
Overall, the authors' responses and revisions effectively address all my previous concerns.
The manuscript is significantly improved in terms of clarity, clinical relevance, and scientific
robustness, making it well-prepared for publication.
Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 2 Date: 04 Apr 2025
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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?
Yes - the author's interpretation is reasonable
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?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have provided a thoughtful, detailed, and
comprehensive revision in response to the reviewer’s comments. Specifically, the authors
have significantly strengthened the manuscript by explicitly addressing key methodological
limitations inherent in Mendelian Randomization (MR), such as residual pleiotropy and
population specificity. The adjustments made in the "Conclusion" section clearly articulate these
potential limitations and provide appropriate recommendations for future research directions.
Additionally, the revised manuscript demonstrates enhanced clarity in discussing specific lipid
species (LPC 18:1 and LPC 20:4), differentiating their clinical implications for Ulcerative Colitis
(UC) and Crohn’s Disease (CD).
Although minor issues remain, including residual concerns about potential pleiotropy indicated
by some significant MR-Egger intercept tests, the authors acknowledged these issues
transparently, suggesting future research directions that could comprehensively address these
concerns.
Overall, the authors' responses and revisions effectively address all my previous concerns.
The manuscript is significantly improved in terms of clarity, clinical relevance, and scientific
robustness, making it well-prepared for publication.
Please review this paper.
user
Title: Unveiling the Influence of Lipidomes on Inflammatory Bowel Disease: A Bidirectional
Mendelian Randomization Study
Version: 2 Date: 04 Apr 2025
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?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with sufficient technical rigor to
allow confidence in the results?
Yes - experiments and analyses were performed appropriately
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?
Yes - the author's interpretation is reasonable
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?
Yes - current version is technically sound
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The authors have provided a thoughtful, detailed, and
comprehensive revision in response to the reviewer’s comments. Specifically, the authors
have significantly strengthened the manuscript by explicitly addressing key methodological
limitations inherent in Mendelian Randomization (MR), such as residual pleiotropy and
population specificity. The adjustments made in the "Conclusion" section clearly articulate these
potential limitations and provide appropriate recommendations for future research directions.
Additionally, the revised manuscript demonstrates enhanced clarity in discussing specific lipid
species (LPC 18:1 and LPC 20:4), differentiating their clinical implications for Ulcerative Colitis
(UC) and Crohn’s Disease (CD).
Although minor issues remain, including residual concerns about potential pleiotropy indicated
by some significant MR-Egger intercept tests, the authors acknowledged these issues
transparently, suggesting future research directions that could comprehensively address these
concerns.
Overall, the authors' responses and revisions effectively address all my previous concerns.
The manuscript is significantly improved in terms of clarity, clinical relevance, and scientific
robustness, making it well-prepared for publication.
assistant