Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 2 Date: 12 Sep 2024
Reviewer's report:
• Many claimed revisions in the response can’t be found in the manuscript at the stated lines.
Just to name one example: comment 3 from reviewer 1, the response said that they have added
a brief overview of the methods and explained why the threshold is chosen in line 160-162, and
line 143-144, but they can’t be found in the manuscript. Please check throughout the manuscript
and fix.
• Regarding the response to comment 1 from reviewer 2 (me), could the authors provide a brief
description of the data they used for MR analysis as they did for NHANES data? Is the data
from clinical EMR? Or something else? How is (major) depression measured in these datasets?
• Can the authors briefly explain how was physical activity as a confounding factor accounted
for in the SNP selection stage? This info should be added to the manuscript as well.
• In the response, the authors tried to explain why the effect sizes (ORs) differ drastically between
MR analysis and NHANES analysis. Is the first reason claiming that GWAS result is less robust?
Also these info should be also added to the discussion section in the manuscript to improve the
quality.
• Regarding the complex relationship between depression and bowl dysfunction (constipation
and diarrhea), could the authors consider including diarrhea in the analysis, so that outcome is
categorical instead of binary? The reference category is patients without either constipation or
diarrhea, and the analysis could show whether depression increased the risk of either one of
them, or both of them. This could also potentially avoid the selection bias.
• The authors indicate that potential bias from MR methodology is included at line 295-297,
again they are not found in the manuscript there.
Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 2 Date: 12 Sep 2024
Reviewer's report:
• Many claimed revisions in the response can’t be found in the manuscript at the stated lines.
Just to name one example: comment 3 from reviewer 1, the response said that they have added
a brief overview of the methods and explained why the threshold is chosen in line 160-162, and
line 143-144, but they can’t be found in the manuscript. Please check throughout the manuscript
and fix.
• Regarding the response to comment 1 from reviewer 2 (me), could the authors provide a brief
description of the data they used for MR analysis as they did for NHANES data? Is the data
from clinical EMR? Or something else? How is (major) depression measured in these datasets?
• Can the authors briefly explain how was physical activity as a confounding factor accounted
for in the SNP selection stage? This info should be added to the manuscript as well.
• In the response, the authors tried to explain why the effect sizes (ORs) differ drastically between
MR analysis and NHANES analysis. Is the first reason claiming that GWAS result is less robust?
Also these info should be also added to the discussion section in the manuscript to improve the
quality.
• Regarding the complex relationship between depression and bowl dysfunction (constipation
and diarrhea), could the authors consider including diarrhea in the analysis, so that outcome is
categorical instead of binary? The reference category is patients without either constipation or
diarrhea, and the analysis could show whether depression increased the risk of either one of
them, or both of them. This could also potentially avoid the selection bias.
• The authors indicate that potential bias from MR methodology is included at line 295-297,
again they are not found in the manuscript there.
Please review this paper.
user
Title: Can depression lead to chronic constipation, or does chronic constipation worsen
depression? NHANES 2005-2010 and bidirectional Mendelian randomization analyses
Version: 2 Date: 12 Sep 2024
Reviewer's report:
• Many claimed revisions in the response can’t be found in the manuscript at the stated lines.
Just to name one example: comment 3 from reviewer 1, the response said that they have added
a brief overview of the methods and explained why the threshold is chosen in line 160-162, and
line 143-144, but they can’t be found in the manuscript. Please check throughout the manuscript
and fix.
• Regarding the response to comment 1 from reviewer 2 (me), could the authors provide a brief
description of the data they used for MR analysis as they did for NHANES data? Is the data
from clinical EMR? Or something else? How is (major) depression measured in these datasets?
• Can the authors briefly explain how was physical activity as a confounding factor accounted
for in the SNP selection stage? This info should be added to the manuscript as well.
• In the response, the authors tried to explain why the effect sizes (ORs) differ drastically between
MR analysis and NHANES analysis. Is the first reason claiming that GWAS result is less robust?
Also these info should be also added to the discussion section in the manuscript to improve the
quality.
• Regarding the complex relationship between depression and bowl dysfunction (constipation
and diarrhea), could the authors consider including diarrhea in the analysis, so that outcome is
categorical instead of binary? The reference category is patients without either constipation or
diarrhea, and the analysis could show whether depression increased the risk of either one of
them, or both of them. This could also potentially avoid the selection bias.
• The authors indicate that potential bias from MR methodology is included at line 295-297,
again they are not found in the manuscript there.
assistant