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: 
25 Feb 2020
Reviewer's report:
This is a description of eight IBS associated SNPs selected to analyze abdominal pain and clinical
management of 2,063 individuals with IBD (1,206 with Crohn's disease and 857 with ulcerative colitis)
via samples stored in the Swiss IBD cohort study (SIBDCS) biobank. The results indicate an association
of pain intensity in patients with ulcerative colitis and two of eight IBS-associated SNPs indicating a
genetic evidence for an overlap of some disease mechanisms between IBD and IBS, whereas no such
association was found for Crohn's disease.
However, the authors will have to explain some issues more in detail.
Major concerns
In this material stored in the SIBDCS biobank solely 8 SNPs were selected although many more SNPs
actually have been related to IBS. Thus, a recent paper from this journal (Zhu S et al. BMC Gastroenterol.
2019 Oct 15;19(1):165) described 66 SNPs - and even more SNPs of interest related to IBS have been
reported elsewhere. Could the authors more detailed disclose how their 8 SNPs were selected as compared
to all existing SNPs related to IBS?
Even clinical features of IBD include "alarm symptoms" like weight loss or bloody diarrhea which might
appear straight forward in case of flaring disease, the clinical situation becomes more complex among
patients with quiescent IBD complaining of abdominal pain, bloating, chronic diarrhea, and/or
constipation mimicking features of IBS. Consequently, many clinicians would like to have valid and
specific tests at hand which could guide them to make the right clinical decisions, e.g. if a patient should
be put on other medications (in case of flaring IBD), or if management should focus on life style and
dietary changes such as avoiding particular foods (e.g. FODMAP) or adding supplements (curcumin or
soluble fibers) to address symptoms. Thus, the treatment guidelines available at present do not precisely
address the IBS/IBD overlap syndrome. Nevertheless, the authors must elaborate more in detail what
information of novelty does this paper actually add to the existing knowledge - or said in another way, the
importance of the data presented in this descriptive paper of 8 SNPs selected need to be highlighted among
several other SNPs of potential interest?
Minor comments
1. The style of the manuscript is unusual as figure legends are incorporated in the text, e.g. legend of
figure 1 is placed on page 10.
2. Throughout the text number of decimals on p-values vary from 2 to 5. A p-value of 0.00042 may be
considered "a bit overkill" (page 12).
3. The conclusion of the present paper is rather vague, especially as the aim of the study is somewhat
blurred.
4. Could an association between IBS SNPs and Crohn's disease be expected in case other SNPs were
chosen?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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:
Acceptable
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.
None
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any
attachments I upload will be posted on the website along with the authors' responses. 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/
). I understand that any comments which I do not wish to be
included in my named report can be included as confidential comments to the editors, which will not be
published.
I agree to the open peer review policy of the journal
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: 
25 Feb 2020
Reviewer's report:
This is a description of eight IBS associated SNPs selected to analyze abdominal pain and clinical
management of 2,063 individuals with IBD (1,206 with Crohn's disease and 857 with ulcerative colitis)
via samples stored in the Swiss IBD cohort study (SIBDCS) biobank. The results indicate an association
of pain intensity in patients with ulcerative colitis and two of eight IBS-associated SNPs indicating a
genetic evidence for an overlap of some disease mechanisms between IBD and IBS, whereas no such
association was found for Crohn's disease.
However, the authors will have to explain some issues more in detail.
Major concerns
In this material stored in the SIBDCS biobank solely 8 SNPs were selected although many more SNPs
actually have been related to IBS. Thus, a recent paper from this journal (Zhu S et al. BMC Gastroenterol.
2019 Oct 15;19(1):165) described 66 SNPs - and even more SNPs of interest related to IBS have been
reported elsewhere. Could the authors more detailed disclose how their 8 SNPs were selected as compared
to all existing SNPs related to IBS?
Even clinical features of IBD include "alarm symptoms" like weight loss or bloody diarrhea which might
appear straight forward in case of flaring disease, the clinical situation becomes more complex among
patients with quiescent IBD complaining of abdominal pain, bloating, chronic diarrhea, and/or
constipation mimicking features of IBS. Consequently, many clinicians would like to have valid and
specific tests at hand which could guide them to make the right clinical decisions, e.g. if a patient should
be put on other medications (in case of flaring IBD), or if management should focus on life style and
dietary changes such as avoiding particular foods (e.g. FODMAP) or adding supplements (curcumin or
soluble fibers) to address symptoms. Thus, the treatment guidelines available at present do not precisely
address the IBS/IBD overlap syndrome. Nevertheless, the authors must elaborate more in detail what
information of novelty does this paper actually add to the existing knowledge - or said in another way, the
importance of the data presented in this descriptive paper of 8 SNPs selected need to be highlighted among
several other SNPs of potential interest?
Minor comments
1. The style of the manuscript is unusual as figure legends are incorporated in the text, e.g. legend of
figure 1 is placed on page 10.
2. Throughout the text number of decimals on p-values vary from 2 to 5. A p-value of 0.00042 may be
considered "a bit overkill" (page 12).
3. The conclusion of the present paper is rather vague, especially as the aim of the study is somewhat
blurred.
4. Could an association between IBS SNPs and Crohn's disease be expected in case other SNPs were
chosen?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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:
Acceptable
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.
None
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any
attachments I upload will be posted on the website along with the authors' responses. 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/
). I understand that any comments which I do not wish to be
included in my named report can be included as confidential comments to the editors, which will not be
published.
I agree to the open peer review policy of the journal
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: 
25 Feb 2020
Reviewer's report:
This is a description of eight IBS associated SNPs selected to analyze abdominal pain and clinical
management of 2,063 individuals with IBD (1,206 with Crohn's disease and 857 with ulcerative colitis)
via samples stored in the Swiss IBD cohort study (SIBDCS) biobank. The results indicate an association
of pain intensity in patients with ulcerative colitis and two of eight IBS-associated SNPs indicating a
genetic evidence for an overlap of some disease mechanisms between IBD and IBS, whereas no such
association was found for Crohn's disease.
However, the authors will have to explain some issues more in detail.
Major concerns
In this material stored in the SIBDCS biobank solely 8 SNPs were selected although many more SNPs
actually have been related to IBS. Thus, a recent paper from this journal (Zhu S et al. BMC Gastroenterol.
2019 Oct 15;19(1):165) described 66 SNPs - and even more SNPs of interest related to IBS have been
reported elsewhere. Could the authors more detailed disclose how their 8 SNPs were selected as compared
to all existing SNPs related to IBS?
Even clinical features of IBD include "alarm symptoms" like weight loss or bloody diarrhea which might
appear straight forward in case of flaring disease, the clinical situation becomes more complex among
patients with quiescent IBD complaining of abdominal pain, bloating, chronic diarrhea, and/or
constipation mimicking features of IBS. Consequently, many clinicians would like to have valid and
specific tests at hand which could guide them to make the right clinical decisions, e.g. if a patient should
be put on other medications (in case of flaring IBD), or if management should focus on life style and
dietary changes such as avoiding particular foods (e.g. FODMAP) or adding supplements (curcumin or
soluble fibers) to address symptoms. Thus, the treatment guidelines available at present do not precisely
address the IBS/IBD overlap syndrome. Nevertheless, the authors must elaborate more in detail what
information of novelty does this paper actually add to the existing knowledge - or said in another way, the
importance of the data presented in this descriptive paper of 8 SNPs selected need to be highlighted among
several other SNPs of potential interest?
Minor comments
1. The style of the manuscript is unusual as figure legends are incorporated in the text, e.g. legend of
figure 1 is placed on page 10.
2. Throughout the text number of decimals on p-values vary from 2 to 5. A p-value of 0.00042 may be
considered "a bit overkill" (page 12).
3. The conclusion of the present paper is rather vague, especially as the aim of the study is somewhat
blurred.
4. Could an association between IBS SNPs and Crohn's disease be expected in case other SNPs were
chosen?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
Yes
Does the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
Yes
Are the conclusions drawn adequately supported by the data shown?
If not, please explain in your comments to the authors.
Yes
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:
Acceptable
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.
None
I agree to the open peer review policy of the journal. I understand that my name will be included on my
report to the authors and, if the manuscript is accepted for publication, my named report including any
attachments I upload will be posted on the website along with the authors' responses. 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/
). I understand that any comments which I do not wish to be
included in my named report can be included as confidential comments to the editors, which will not be
published.
I agree to the open peer review policy of the journal
assistant