PONE-D-22-04764Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: An updated meta-analysis of 14 case-control studiesPLOS ONE

Dear Dr. Yao,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript is a meta-analysis of the association between Tumor Necrosis Factor-α-308G/A polymorphism and obstructive sleep apnea. The statistical analysis of 14 case-control studies selected for this review was conducted rigorously and this meta-analysis is appropriately based on the Prisma checklist. The introduction of this manuscript reported previous meta-analyses in this area and explained that they included additional case-control studies.

The conclusions are based on the findings obtained through adequate statistical analysis. However, the discussion should include some limitations related to the genetic association studies and the fact that the studies included in this meta-analysis did not report the effect of AIH (apnea, hypoapnea index), oxygen saturation levels, arousals, comorbidities, sex, age, and other factors that could play an important role in the pathophysiology of the obstructive sleep apnea.

The methodology is appropriate and rigorous. The inclusion and exclusion criteria are well formulated. The statistical analysis used in this meta-analysis included: Pearson’s χ2 test performed to evaluate the Hardy–Weinberg equilibrium (HWE), Cochran’s Q and the I2 statistics to evaluate heterogeneity, Z and OR test to evaluate genetic models, Harbord funnel plot and Peters test to identify publication bias. The results of these analyses are shown in tables and figures (forest plots, Harbord funnel plot) and show complete information about the association between Tumor Necrosis Factor-α-308G/A polymorphism and obstructive sleep apnea reported in case-control studies.

Data from each case-control study is described in the manuscript. Prisma checklist is supporting information. Complete and broad statistic results are shown. The references included the articles selected for this meta-analysis and previous meta-analyses among others.

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Reviewer #1: Yes: Liliana Otero

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Submitted filename: PLOS ONE Reviewer TNFa.pdf

PONE-D-22-04764R1Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: An updated meta-analysis of 14 case-control studiesPLOS ONE

Dear Dr. Yao,

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.

Please submit your revised manuscript by Apr 06 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Cho Naing, MBBS, PhD, FRCP

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments (if provided):

Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: An updated meta-analysis of 14 case-control studies

Abstract

Line # 31

OSA was used for the first time in this section; kindly spell it out.

Line # 35

Please replace the term ‘used” with “accessed”

As the authors describe how to estimate association in the current metanalysis, it should be "pooled odds ratio or summary odds ratio."

Line # 40-42; Line # 44-45; Line # 48-49

Please provide number of studies for the respective effect estimates.

Line # 49-50

“Substantial between-study heterogeneity” is preferable.

“ p value” of the I2 test should be deleted.

Line # 51

Better to describe as “Source of control participants”.

What sensitivity analysis is it for? Please provide specifically.

Sensitivity analysis for "source of control participants" was reported in the text.

In the abstract, I feel a lack of recommendation in the conclusions. Based on the study limitations that the authors identified during the current research, please suggest future well-designed case control studies, etc.

TEXT

Line # 87

Please omit the word "an updated". Publications from the past were not done by this team.

Search Strategy

Please provide “search strategy for PubMed and Embase in supplementary so that the audiences can replicate.

Line #101

Criteria # 1 is a doubtful. Did you select studies that showed only susceptible to OSA, but not protective. In earlier part, the authors claimed that “the results (from single studies) remained controversial and ambiguous”.

The authors should have selected studies that assessed association between TNF-α-308G/A polymorphisms and OSA (regardless of direction of association)

Line # 111

“The definition of OSA was as described in the primary studies” is preferable.

Line # 117

HWE should have been spelled out as the authors didn't use an abbreviation.

Line # 120

"Missing" is preferable than "ambiguous" as a description.

Line # 124

To the best of my understanding, the NOS checklist is a 9-star tool, with 9 being the highest possible star/score. It is impossible to score more than 9.

Line # 117

The abbreviation HWE may be used at this juncture (please refer to my comments on line #117).

Line # 155; 172-175; 178 Please provide number of studies for the respective effect estimates.

Line #188

This should come at the top of this paragraph.

Line # 198

For the dominant model and heterozygous models, please provide p values. What about the remaining models?

Please remove p value for I2 test.

Table #2

Please remove the last column with I2 test p value.

Discussion

This section requires more efforts.

As this is a meta-analysis, citations to individual studies should be reduced/shortened.

Please briefly describe how the current study and previous reviews in this field are compared and contrasted.

Please use a subheading of the “study limitations” for clarity

To add a recommendation as a concluding remark. Please note my recommendation for this section of the abstract.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The manuscript was well written. Introduction clearly and adequately stated the background of the current issue of the obstructive sleep apnea. Nevertheless, there are some suggestions as follow.

Results:

Table 1- Basic Characteristics of included studies

In this table, suggest to provide reference number in addition to author names.

In figures, it would be great if authors could provide the forest plots of effect estimates for each genetic models as a supplemenatary file.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

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PONE-D-22-04764R2Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: An updated meta-analysis of 14 case-control studiesPLOS ONE

Dear Dr. Yao,

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.

Please submit your revised manuscript by Jun 16 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're 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.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Cho Naing, MBBS, PhD, FRCP

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: An updated meta-analysis of 14 case-control studies"

The authors still need to revise an array of points. I also recommend reviewing the manuscript for language proficiency.

Title

Regarding my background comments, the phrase "an updated" has to be removed from the title.

Previous publications were not done by this team.

Abstract

Line #32………. “Obstructive” should not be capitalized

Line #41……… Please include the names of genetic models that were created for overall population. I believe that overall population was assessed using five different genetic models such as allele. "Dominant, recessive, homozygous, and heterozygous models"

Line # 47, 49……….. To spell out HB and PB

Line # 50…………. Name the genetic models for AA in comparison to GG, AG/GG

Line # 53…………. The statement "a leave-one-out meta-analysis" should be applied.

Line # 56……… Take out the word “also”

TEXT

Line # 63……….. replacing "published studies reported" for "increasing evidence has demonstrated" Line # 68/ 69………. Please rephrase this sentence. The word "thus" was used twice

Line # 72………. The wording "by Szily and coworkers or By Szily and associates" should have been used.

Line # 72………. Replace the word "strong evidence" with lighter tone, like "published studies."

Line # 78, 79, 80…… The authors could combine these two sentences into one and then cite [13] afterward.

Line # 90………. “Hence” is a preferrable term.

Line # 92………. “Source of the control participants”

Line # 114……… Please, remove “additionally”.

Line # 133……… Please keep "homozygous" and "heterozygous" while removing "codominant."

Line # 138……The word .”Otherwise” is preferrable to “By contrast”..

Line # 141……. So as to differentiate it from statistical models (Random. Fixed models), it needs to be mentioned as "for all genetic models".

Line # 141-142………… Are you referring to "a leave-one-out metanalysis" for the stability of the results.

Line # 146……… Literature search and characteristics of included studies.

Please separate the subheadings into two sections, such as "Selection of Studies" and "Characteristics of the Included Studies."

Line # 157……… This sentence should be placed at the beginning of paragraph, “Selection of studies”.

Line # 160, 165 and 166……… It is better to use "eligible". (Please follow this suggestion wherever it is applicable.)

Line # 162……… Source of the control participants?

Line # 167-168……… Please rephrase this sentence.

Table 1…….. Footnotes are incomplete. HB? PB?

Last column…….. Quality score?

Line # 175……… Please add the names of the genetic models for the audiences' convenience. Apply this recommendation to Table 2 as well by including a new column for the genetic model's name.

Line # 204-205………Please clearly indicate that the results are "results of a leave-one-out metanalysis" (also see my comments on Lines 53 and 141–142).

Study limitations

Line # 273…………….. Stability is an appropriate term. What about the reliability? Which analysis/results captured the reliability?

Line # 273…………….. Language bias or information bias?

Line # 275-283……………..Please rephrase the sentences and shorten it.

First, language bias/informational bias? Second, the confounding bias created by……. Third, not all studies conform to the HWE. So, what type of bias? Fourth, there could be additional factors that have not been included in this review.

Acknowledgements

Are you thanking your research team members or the participants and researchers in the studies included in your review? Please clarify.

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[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.]

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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Association of Tumor Necrosis Factor-α-308G/A polymorphism with the risk of obstructive sleep apnea: A meta-analysis of 14 case-control studies

PONE-D-22-04764R3

Dear Dr. Yao,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- 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.

Kind regards,

Cho Naing, MBBS, PhD, FRCP

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have improved the manuscript, accordingly.

Thank you.

Reviewers' comments: