Reviewer ’s report  
 
Title:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 30 Sep 2016 
 
Reviewer:  Reza  Ghassemifar  
 
Reviewer’s report:  
 
The authors of the current study investigated single nucleotide polymorphisms (SNP) located in 
genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD.  
 
 According to their results the two strongest alle lic associations were observed between IBD and 
SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker 
(rs6689879) contributed to increased ileal MAGI3 expression level in non -IBD controls. 
Furthermore, association between inflammation an d decreased expression levels of MAGI3, 
PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased 
expression of PTPN22 in colonic IBD 36 mucosa, was observed  
 
Comments:  
 
Genetic associations were studied in a cohort of 1 38 adult IBD and 157 CD or UC patients. 
Controls were a pool of randomly selected individuals (n=423) from anonymized regional DNA 
bank all living in the south -eastern part of Sweden (Table 1, subgroup 1). A second Swedish 
cohort was used in follow up stud y.  
 
The study has delivered the initial aim and has shown that there is a genetic basis for modulation 
of the intestinal epithelial barrier in IBD, which in turn points to a complex regulation of TJ gene 
expression via a secondary role of inflammation. Al so using genetically homogenous cohort 
(Swedish population) they have been able to identified MAGI3 as a new candidate gene for IBD.  
 
Over all, the work is adequately controlled and the results are sound. The findings are new 
information and will be useful for both scientists and clinicians in this field.  
 
Are the m ethods 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 sta tistical 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 o f 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.  
 
I agree to the open peer review policy of the journal. I understand that my name wil l 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 und er 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 a s 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:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 30 Sep 2016 
 
Reviewer:  Reza  Ghassemifar  
 
Reviewer’s report:  
 
The authors of the current study investigated single nucleotide polymorphisms (SNP) located in 
genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD.  
 
 According to their results the two strongest alle lic associations were observed between IBD and 
SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker 
(rs6689879) contributed to increased ileal MAGI3 expression level in non -IBD controls. 
Furthermore, association between inflammation an d decreased expression levels of MAGI3, 
PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased 
expression of PTPN22 in colonic IBD 36 mucosa, was observed  
 
Comments:  
 
Genetic associations were studied in a cohort of 1 38 adult IBD and 157 CD or UC patients. 
Controls were a pool of randomly selected individuals (n=423) from anonymized regional DNA 
bank all living in the south -eastern part of Sweden (Table 1, subgroup 1). A second Swedish 
cohort was used in follow up stud y.  
 
The study has delivered the initial aim and has shown that there is a genetic basis for modulation 
of the intestinal epithelial barrier in IBD, which in turn points to a complex regulation of TJ gene 
expression via a secondary role of inflammation. Al so using genetically homogenous cohort 
(Swedish population) they have been able to identified MAGI3 as a new candidate gene for IBD.  
 
Over all, the work is adequately controlled and the results are sound. The findings are new 
information and will be useful for both scientists and clinicians in this field.  
 
Are the m ethods 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 sta tistical 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 o f 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.  
 
I agree to the open peer review policy of the journal. I understand that my name wil l 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 und er 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 a s 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:  Genetic variation and expression levels of tight junction genes identifies association 
between MAGI3 and inflammatory bowel disease  
 
Version: 0 Date: 30 Sep 2016 
 
Reviewer:  Reza  Ghassemifar  
 
Reviewer’s report:  
 
The authors of the current study investigated single nucleotide polymorphisms (SNP) located in 
genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD.  
 
 According to their results the two strongest alle lic associations were observed between IBD and 
SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker 
(rs6689879) contributed to increased ileal MAGI3 expression level in non -IBD controls. 
Furthermore, association between inflammation an d decreased expression levels of MAGI3, 
PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased 
expression of PTPN22 in colonic IBD 36 mucosa, was observed  
 
Comments:  
 
Genetic associations were studied in a cohort of 1 38 adult IBD and 157 CD or UC patients. 
Controls were a pool of randomly selected individuals (n=423) from anonymized regional DNA 
bank all living in the south -eastern part of Sweden (Table 1, subgroup 1). A second Swedish 
cohort was used in follow up stud y.  
 
The study has delivered the initial aim and has shown that there is a genetic basis for modulation 
of the intestinal epithelial barrier in IBD, which in turn points to a complex regulation of TJ gene 
expression via a secondary role of inflammation. Al so using genetically homogenous cohort 
(Swedish population) they have been able to identified MAGI3 as a new candidate gene for IBD.  
 
Over all, the work is adequately controlled and the results are sound. The findings are new 
information and will be useful for both scientists and clinicians in this field.  
 
Are the m ethods 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 sta tistical 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 o f 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.  
 
I agree to the open peer review policy of the journal. I understand that my name wil l 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 und er 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 a s confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant