ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico

Julian Ramírez-Bello; Celi Sun; Guillermo Valencia-Pacheco; Bhupinder Singh; Rosa Elda Barbosa-Cobos; Miguel A. Saavedra; Ricardo F. López-Villanueva; Swapan K. Nath

doi:10.1371/journal.pone.0224543

Peer Review History

Original SubmissionAugust 23, 2019
30 Aug 2019 Decision Letter - Amr H Sawalha, Editor PONE-D-19-23844 ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico PLOS ONE Dear Dr. Nath, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. We would appreciate receiving your revised manuscript by Oct 14 2019 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. 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Additional Editor Comments: The work by Ramirez-Bello and colleagues evaluate the well-established genetic association between ITGAM and lupus in 2 cohorts from Mexico. They replicate this genetic association in 2 Mexican populations and provide results suggesting a possible protective effect of ITGAM lupus-associated haplotype against RA. The is straight forward work, well written, and replication of this genetic association in Mexican populations is worth reporting. The authors need to address the following points before this can be accepted for publication: 1) As the authors are well aware, the single most important limitation in this work is the lack of ability, by study design, to assess and correct for population stratification. This is major issue in admixed populations such as in Mexico. This limitation although mentioned briefly in the manuscript, should be emphasized and also mentioned in the abstract. On the positive side, the authors did study patients and controls matched by region (central Mexico versus Yucatan). 2) The association between ITGAM and lupus in the Yucatan population is likely inflated as a result of low power and small sample size. This should be also noted in the abstract. Power has been estimated, and in particular given low power in the Yucatan cohort it is important to attempt to correct the odds ratio for inflation as a function of power similar to an approach used to calculate winner's curse effect. 3) Please attempt to preform a meta-analysis combining both Yucatan and Central Mexico lupus cohort. 4) Other minor points: - Please amend the first sentence in the conclusion to say "Our data show that all four ITGAM SNPs are significantly associated with susceptibility to SLE in patients from Mexico" - Table 1 legend should say "Central Mexico" - Table 3 RA findings are not from Yucatan but from Central Mexico. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0224543.r001
Revision 1
11 Oct 2019 Author Response Response to the Reviewers comments. The work by Ramirez-Bello and colleagues evaluates the well-established genetic association between ITGAM and lupus in two cohorts from Mexico. They replicate this genetic association in two Mexican populations and provide results suggesting a possible protective effect of ITGAM lupus-associated haplotype against RA. This is straight-forward work, well written, and replication of this genetic association in Mexican populations is worth reporting. The authors need to address the following points before this can be accepted for publication: Thank you for reviewing our manuscript, and here are our point-by-point responses to the comments. Q1) As the authors are well aware, the single most important limitation in this work is the lack of ability, by study design, to assess and correct for population stratification. This is major issue in admixed populations such as in Mexico. This limitation although mentioned briefly in the manuscript, should be emphasized and also mentioned in the abstract. On the positive side, the authors did study patients and controls matched by region (central Mexico versus Yucatan). Response: Yes, we agree with the reviewer regarding limitation of this study. As reviewer appreciated that to minimize the effect of population stratification, we have used the ethnicity-matched cases and controls from the Central Mexico and Yucatan. Now we have mentioned this in abstract and in the text. Q2) The association between ITGAM and lupus in the Yucatan population is likely inflated as a result of low power and small sample size. This should be also noted in the abstract. Power has been estimated, and in particular given low power in the Yucatan cohort it is important to attempt to correct the odds ratio for inflation as a function of power similar to an approach used to calculate winner's curse effect. Response: Yes, we agree that association results from Yucatan are likely to be inflated due to the small samples sizes, especially due to the low allele frequency, and now we have mentioned this in the abstract. As you suggested, we have performed a meta-analysis, which is adjusted by the samples sizes. As expected, the minor allele frequencies and ORs are in consistent with the directionality, although there is a significant heterogeneity of ORs. We have provided all this information in the Supplementary Table 1. Q3) Please attempt to perform a meta-analysis combining both Yucatan and Central Mexico lupus cohort. Response: Yes, we have performed a meta-analysis, and information is provided in the Supplementary Table 3. 4) Other minor points: - Please amend the first sentence in the conclusion to say: "Our data show that all four ITGAM SNPs are significantly associated with susceptibility to SLE in patients from Mexico." Response: Done, thank you. - Table 1 legend should say "Central Mexico" Response: Corrected, thank you. - Table 3 RA findings are not from Yucatan but from Central Mexico. Response: Corrected. Thank you. Attachments Attachment Submitted filename: Response_to_Reviewers_10_9_19.docx https://doi.org/10.1371/journal.pone.0224543.r002
17 Oct 2019 Decision Letter - Amr H Sawalha, Editor ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico PONE-D-19-23844R1 Dear Dr. Nath, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. With kind regards, Amr H Sawalha Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0224543.r003
Formally Accepted
20 Nov 2019 Acceptance Letter - Amr H Sawalha, Editor PONE-D-19-23844R1 ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico Dear Dr. Nath: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Amr H Sawalha Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0224543.r004

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