Reviewer’s report
Title: 
Abdominal pain in patients with inflammatory bowel disease – Association with single-nucleotide
polymorphisms prevalent in irritable bowel syndrome and clinical management
Version: 
2 
Date: 
22 May 2020
Reviewer's report:
The authors have undertaken an interesting study about a remarkably poorly understood phenomenon in
inflammatory bowel disease (IBD): abdominal pain. 
The basic concepts underlying this manuscript and the
results are interesting. 
However, there are several conceptual and methodological concerns that I have
which severely limit my enthusiasm for this work. 
The decision-making behind key elements of the
approach (ex: using "maximum pain" as a primary outcome and the specific SNPs that were selected for
this analysis) is poorly explained and is, in my opinion, severely flawed. 
Abdominal pain, in and of itself,
does not define IBS. 
As the authors themselves state in the Discussion, the concept of using only a
measure of pain to try to make a link to IBS in IBD is problematic. 
Ideally, they should have used Rome
criteria to differentiate their study cohorts. 
Without that, this whole study is based on very shaky ground. 
If
that major issue is disregarded, there are other significant problems with the study design. 
Using
maximum pain is not ideal and there's not much of a precedent for this in the literature (ex: understanding
the limitation of the survey tools the authors had at their disposal, why not use any pain vs. no pain over
the study period?). 
There are potential rationales for using this measure over others but the reasoning is
not explained anywhere. 
Beyond this, the specific SNPs chosen in the analysis seem reasonable but the
overall list is missing several other important candidates that were even described in the references
described in the Methods section (ex: including SCN5A and SERT promoter polymorphisms). 
There is no
explanation for why they chose the SNPs they did. While the resultant analysis is interesting, without using
a more comprehensive and reasonably updated list of SNPs, their approach appears arbitrary and less
convincing. 
I would not support proceeding to publication without major revisions addressing the issues
described above.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If an additional statistical review is recommended, please specify what aspects require further assessment
in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this manuscript,
either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization that holds or has
applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your
reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (
 http://creativecommons.org/licenses/by/4.0
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy for us to publish this report, please contact the editorial office before completing
the review.
If you wish, you can include your name in your published report. Please note you must decide whether
to include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
Reviewer’s report
Title: 
Abdominal pain in patients with inflammatory bowel disease – Association with single-nucleotide
polymorphisms prevalent in irritable bowel syndrome and clinical management
Version: 
2 
Date: 
22 May 2020
Reviewer's report:
The authors have undertaken an interesting study about a remarkably poorly understood phenomenon in
inflammatory bowel disease (IBD): abdominal pain. 
The basic concepts underlying this manuscript and the
results are interesting. 
However, there are several conceptual and methodological concerns that I have
which severely limit my enthusiasm for this work. 
The decision-making behind key elements of the
approach (ex: using "maximum pain" as a primary outcome and the specific SNPs that were selected for
this analysis) is poorly explained and is, in my opinion, severely flawed. 
Abdominal pain, in and of itself,
does not define IBS. 
As the authors themselves state in the Discussion, the concept of using only a
measure of pain to try to make a link to IBS in IBD is problematic. 
Ideally, they should have used Rome
criteria to differentiate their study cohorts. 
Without that, this whole study is based on very shaky ground. 
If
that major issue is disregarded, there are other significant problems with the study design. 
Using
maximum pain is not ideal and there's not much of a precedent for this in the literature (ex: understanding
the limitation of the survey tools the authors had at their disposal, why not use any pain vs. no pain over
the study period?). 
There are potential rationales for using this measure over others but the reasoning is
not explained anywhere. 
Beyond this, the specific SNPs chosen in the analysis seem reasonable but the
overall list is missing several other important candidates that were even described in the references
described in the Methods section (ex: including SCN5A and SERT promoter polymorphisms). 
There is no
explanation for why they chose the SNPs they did. While the resultant analysis is interesting, without using
a more comprehensive and reasonably updated list of SNPs, their approach appears arbitrary and less
convincing. 
I would not support proceeding to publication without major revisions addressing the issues
described above.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If an additional statistical review is recommended, please specify what aspects require further assessment
in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this manuscript,
either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization that holds or has
applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your
reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (
 http://creativecommons.org/licenses/by/4.0
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy for us to publish this report, please contact the editorial office before completing
the review.
If you wish, you can include your name in your published report. Please note you must decide whether
to include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
Please review this paper.
user
Reviewer’s report
Title: 
Abdominal pain in patients with inflammatory bowel disease – Association with single-nucleotide
polymorphisms prevalent in irritable bowel syndrome and clinical management
Version: 
2 
Date: 
22 May 2020
Reviewer's report:
The authors have undertaken an interesting study about a remarkably poorly understood phenomenon in
inflammatory bowel disease (IBD): abdominal pain. 
The basic concepts underlying this manuscript and the
results are interesting. 
However, there are several conceptual and methodological concerns that I have
which severely limit my enthusiasm for this work. 
The decision-making behind key elements of the
approach (ex: using "maximum pain" as a primary outcome and the specific SNPs that were selected for
this analysis) is poorly explained and is, in my opinion, severely flawed. 
Abdominal pain, in and of itself,
does not define IBS. 
As the authors themselves state in the Discussion, the concept of using only a
measure of pain to try to make a link to IBS in IBD is problematic. 
Ideally, they should have used Rome
criteria to differentiate their study cohorts. 
Without that, this whole study is based on very shaky ground. 
If
that major issue is disregarded, there are other significant problems with the study design. 
Using
maximum pain is not ideal and there's not much of a precedent for this in the literature (ex: understanding
the limitation of the survey tools the authors had at their disposal, why not use any pain vs. no pain over
the study period?). 
There are potential rationales for using this measure over others but the reasoning is
not explained anywhere. 
Beyond this, the specific SNPs chosen in the analysis seem reasonable but the
overall list is missing several other important candidates that were even described in the references
described in the Methods section (ex: including SCN5A and SERT promoter polymorphisms). 
There is no
explanation for why they chose the SNPs they did. While the resultant analysis is interesting, without using
a more comprehensive and reasonably updated list of SNPs, their approach appears arbitrary and less
convincing. 
I would not support proceeding to publication without major revisions addressing the issues
described above.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
No
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Unable to assess
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
No
Are you able to assess any statistics in the manuscript or would you recommend an additional
statistical review?
If an additional statistical review is recommended, please specify what aspects require further assessment
in your comments to the editors.
I am able to assess the statistics
Quality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being published
Declaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of this manuscript,
either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an organization that holds or has
applied for patents relating to the content of the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this paper?
If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your
reply is yes to any, please give details below.
I declare that I have no competing interests
Reviewer Publication Consent.
 I agree for my report to be made available under an Open Access
Creative Commons CC-BY License (
 http://creativecommons.org/licenses/by/4.0
) if this manuscript is
accepted for publication. Any comments that I do not wish to be included in the published report have
been included as confidential comments to the editor, which will not be published.
If you are not happy for us to publish this report, please contact the editorial office before completing
the review.
If you wish, you can include your name in your published report. Please note you must decide whether
to include your name at the start of the process and confirm this decision whenever prompted. If you
change your decision later, we will not be able to publish your name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name with my report. (default)
assistant