PONE-D-24-05576Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profilePLOS ONE

Dear Dr. Kuchler,

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PLOS ONE

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Reviewers' comments:

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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

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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: Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profile

Thank you for submitting your article. This study investigated the association between different vertical facial profiles and SNPs in RUNX2, BMP2, BMP4, and SMAD6. It is a good topic and well written paper. I feel that is appropriate information to the Plos One and I have just a few considerations to do:

1- Abstract.

Page 2, line 36. You said “American Board of Orthodontics (angle formed....)”. You don’t need this information in abstract (angle formed by the intersection of anterior cranium base and mandibular plane lines), only in MM.

2- Introduction.

Page 3, there are typos like: line 59, “strongly associated”; line 63: “have harmonious”; line 66: “involves interactions”. Please review entire paper.

3- Material and methods.

Page 5, line 120: “American Board of Orthodontics”. Here you cant put that information from abstract. Line 122: You said “two experienced orthodontists”, How many years?

4- Discussion.

Page 8, line 198: the same typos, “development contributes”, please review entire paper.

Page 8, line 203. “Once these SNPs are associated.............to the establishment of new preventative therapies.” Is this information the clinical relevance of your paper? If yes, please make this clear.

5- References.

Please insert references from 2024.

Reviewer #2: The present study aimed to investigate the association between different vertical facial profiles and SNPs in RUNX2, BMP2, BMP4, and SMAD6.

Abstract: the aim should be clearer. Which SNPs?

In the introduction and discussion, I suggest that the authors evaluate the possibility of including more recent articles (2022 to 2024) so that the current state of the art on the subject is represented.

In general, English should be revised. Some words are spelled incorrectly, or together. For exemple: Gernerally.

The order of the session of materials and methods should be reviewed. Study size need to be one of the first subtopics.

The tables need to be sequentially numbered based on their order of appearance in the text.

I request authors to revise the titles of all tables to ensure they are self-explanatory and easily understandable.

How were the 7 SNPs chosen? This should be discussed in the discussion section.

I suggest that the authors include a paragraph with the clinical relevance of the study in the Discussion Session.

I kindly request that the authors carefully review the standards and guidelines set forth by the journal for their articles.

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Reviewer #1: No

Reviewer #2: No

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Single Nucleotide Polymorphisms in RUNX2 and BMP2 contributes to different vertical facial profile

PONE-D-24-05576R1

Dear Dr. Kuchler,

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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Kind regards,

Gaetano Isola, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have made all requested changes. The manuscript can be accepted for publication.

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 #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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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 #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

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 #1: Yes

Reviewer #2: Yes

**********

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 #1: Yes

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 #1: All corrections suggested by this reviewer were made and improved the paper, so I recommend acceptance.

Reviewer #2: The present study aimed to investigate the association between different vertical facial profiles and SNPs in RUNX2, BMP2, BMP4, and SMAD6.

After the complete revision of the manuscript, the authors resolved the elucidated concerns, made all the corrections, and addressed all indicated issues.

Overall, the manuscript is improved and presents an interesting topic with results that can provide significance in clinical application. The authors resolved the elucidated concerns, made all the corrections, and addressed all indicated issues.

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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 #1: No

Reviewer #2: No

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