PONE-D-23-35781SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPDPLOS ONE

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Additional Editor Comments :

Hello,

Please go through the reviewers comments as below raised by the reviewer and answer them accordingly.

Ganbold et al. reported the SNP-SNP and SNP-environment positive interactions between MMP2 rs243864, MMP12 rs652438 associated with increased risk of COPD among Mongolian population. Moreover, smoking-related factors were also evaluated. It provides evidence of distinct populations and underscores the potential value of clinical intervention. However, there are still some issues that need clarification.

Major:

1. Was all p-value adjusted after multiple comparison? For example, Table 3, Table 4, and Table 5.

2. Page 9. Line153. Only recessive model was remaining after comparing the genotype frequency. I am confused about Table 4. The genotype frequencies of each SNP need to be calculated for both the COPD and control groups.

Minor:

1. Table 5. After adding rs1799750, rs11646643, and rs3918253, there is no significant difference. Do all three of these SNPs collectively exhibit a risk-resistant factor for COPD?

2, Page 11, line 169, “we found positive interaction … had increased risk for COPD” The interaction mechanism of rs243864 in MMP2 and rs652438 in MMP12 should be discussed.

Thank you.

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Reviewers' comments:

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Reviewer #1: Yes

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

Reviewer #1: I Don't Know

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Reviewer #1: Yes

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Reviewer #1: Yes

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5. Review Comments to the Author

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Reviewer #1: Ganbold et al. reported the SNP-SNP and SNP-environment positive interactions between MMP2 rs243864, MMP12 rs652438 associated with increased risk of COPD among Mongolian population. Moreover, smoking-related factors were also evaluated. It provides evidence of distinct populations and underscores the potential value of clinical intervention. However, there are still some issues that need clarification.

Major:

1. Was all p-value adjusted after multiple comparison? For example, Table 3, Table 4, and Table 5.

2. Page 9. Line153. Only recessive model was remaining after comparing the genotype frequency. I am confused about Table 4. The genotype frequencies of each SNP need to be calculated for both the COPD and control groups.

Minor:

1. Table 5. After adding rs1799750, rs11646643, and rs3918253, there is no significant difference. Do all three of these SNPs collectively exhibit a risk-resistant factor for COPD?

2, Page 11, line 169, “we found positive interaction … had increased risk for COPD” The interaction mechanism of rs243864 in MMP2 and rs652438 in MMP12 should be discussed.

**********

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Reviewer #1: No

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Dear Dr. Jambaldori,

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.

The authors have answered most of the questions raised by the reviewers that improved the quality of this manuscript. 

Kind regards,

Mohd Hussain Shah, PhD.

Guest Editor

PLOS ONE