PONE-D-23-17201Associations between birth variables and adult apolipoproteins: The LifeGene CohortPLOS ONE

Dear Dr. Sharma,

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PLOS ONE

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"The LifeGene Study has been funded by the Torsten and Ragnar Söderbergs Foundation, AFA Insurance, Karolinska Institute, the Stockholm County Council, and the Swedish Research Council."

Please state what role the funders took in the study. If the funders had no role, please state: ""The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."" 

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"We wish to thank Professor Nancy Pedersen, Karolinska Institute, the Principal Investigator of the LifeGene cohort, for her help with the data set, and data manager Anders Dahlin, Malmö, for technical support.

The LifeGene cohort was supported by start-up funding received from Karolinska Institute, the Stockholm County Council, and the Swedish Research Council. Funding has also been obtained from the Torsten and Ragnar Söderbergs Foundation and AFA Försäkringar."

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Additional Editor Comments:

Reviewer 1,

Review

Title: Associations between birth variables and adult apolipoproteins: The LifeGene Cohort

Abstract

- Methods: the sentence in lines 70 to 72 should be the last sentence of your methods section. You may want to mention the things you did first and the last ones last.

Results

- Line 77 should go to the methods section.

- Who was the majority between males and females? Include that information with frequency (%).

- Show the results for triglycerides. This sentence sounds like a conclusion “No independent association was found with total cholesterol, but with triglyceride levels”

Conclusion

- Is there a clinical or public health recommendation that authors can give based on their findings? It would be nice to see it.

Keywords- Line 88, how is epidemiology a keyword when there is no mention of it in the abstract?

Introduction

- Line 99 delete etc. and be specific. You probably have to add dyslipidemia, hypertension and abdominal obesity which are components of metabolic syndrome.

Materials and Methods

- Line 120, should be “Study participants”

- Line 125, sampling or sample?

- Line 127, what was provided electronically?

- Lines 128 to 129, apart from the in-person testing, what was the other way of testing? Please include some details.

- Figure 1, last box, what do you mean by “staring”? It would be nice also to see a box with the number of participants on which the analysis was based for this study.

- The sentence beginning line 148 and ending line 150 should go to the section on ethical considerations. If you don’t have one, please have one and take all the ethical issues there.

- Study variables: authors should state the primary outcome/s (dependent variable) and secondary outcome/s

- Line 156, “Have you smoked more than 100 cigarettes in your entire life?” cite where you obtained this standard. Does this mean that if one smokes more than 100 cigarettes then they have a heightened risk of CVD?

- Lines 157 to 158, I don’t think this is part of the “study variable” but a study procedure “The non-fasting blood samples were drawn at LifeGene test centers”, revise accordingly. I encourage the authors to have a subsection on “Study procedures” separate from the “study variables” so that lines 157 to 163 can go there.

- Authors should have a section for “definitions” e.g the smoking of 100 cigarettes, calculation of BMI and apoB/apoA1 ratio.

- Lines 164 to 166, delete because it has already been stated above (section on study sample)

Results

- Line 184, how many were males and females? Only state the majority.

- I don’t understand why Table 1 was based on sex (male and female), does it mean, the authors were also looking at the sex differences in the outcomes? If not please delete.

- This section can be divided as follows:

o 1. “Characteristics of the study participants”, where you describe the distribution of different study variables, NO need to show the table.

o 2. Table 1 association between ApoA1 and independent variables

o 3. Table 2 do the same for ApoB

o 4. Table 3 do the same for ApoA1/ApoB ratio

o 5. Table 4 do the same for triglycerides

o 6. Table 5 do the same for total cholesterol.

- NOTE: each table should have its own subheading and narrations. All the narrations should be above the table. Narrate the significant findings first.

- All significant findings in the models should be narrated/interpreted.

- Since total cholesterol is part of the outcome, the results should be included in the main text NOT as supplementary.

Discussion

- Line 251, delete the p-value. Do the same for line 257

- The section is well-written

Conclusion.

- The section is well-written

Reviewer 2

The manuscript by Sharma et al “’Associations between birth variables and adult apolipoproteins: The LifeGene Cohort” is interesting and presents original findings that add new information to literature. The sample size is large enough to make valid inferences. The paper can benefit from a few suggestions to further improve it.

Minor

1. This study is a cross-section study using participants from another prospective study (The LifeGene Study). This needs to be clear in the methods of both the abstract and main text

2. Am not sure if the usage of “adult” before “apolipoprotein” is appropriate in the title and abstract. Does adult refer to the type of apolipoproteins (not sure if we do refer to them as such) or the age category of the participant being studied? Consider editing the title/abstract to avoid the confusion. Also, “variables” can be substituted with “characteristics” or another term.

3. It appears birth weight and gestation age are the only birth characteristics referred to and mostly birth weight appears to be central to the study. I would suggest for the title to be more reflective of the main findings. However, this is not major and feel free to ignore

4. The primary outcome variable needs to be specified for the manuscript to be more focused to avoid a fishing expedition type of aim: is it apoA1 or apoB or their ratio? In my opinion, apoB/ApoA1 ratio should be the primary out as it is a better risk marker than individual apolipoproteins under discussion.

5. Abstract lines 82-83. It’s no clear which outcome was not associated with cholesterol/was associated with triglycerides

6. Lines 106-107. The authors themselves have indicated that Multiple factors, including lifestyle, dietary habits, and genetic makeup, influence the serum concentration of apolipoproteins and yet they have not clearly written this in their limitation section for related factors that they did not include in their study but with potential to confound the results

7. Inclusion criteria should be more specific i.e what was the age of inclusion? Adults aged 18 years and above or even children where included? See lines 121 vs 126

8. The flow of the Methods section needs some editing. Please follow reporting guidelines https://www.equator-network.org/ . The strobe checklist is used but reporting ad writing format especially in methods does not clearly indicate the subheadings for proper flow

9. In the results section it’s better to indicate the “n” for each variable and only for variables that had an “n” lower than the actual sample size. In Table 1, the meaning of N (sample)* is not clear

10. What criteria was used to arrive at 1 100 cigarettes? Why not 50 or 200 etc? See table 1

11. Table 2 tittle does not reflect what is in the table. Further the words in the cells /rows are not aligned properly. Consider using a row for each subcategory vs using one row for each variable combined with subcategories

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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: No

Reviewer #2: Yes

**********

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

**********

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: Review

Title: Associations between birth variables and adult apolipoproteins: The LifeGene Cohort

Abstract

- Methods: the sentence in lines 70 to 72 should be the last sentence of your methods section. You may want to mention the things you did first and the last ones last.

Results

- Line 77 should go to the methods section.

- Who was the majority between males and females? Include that information with frequency (%).

- Show the results for triglycerides. This sentence sounds like a conclusion “No independent association was found with total cholesterol, but with triglyceride levels”

Conclusion

- Is there a clinical or public health recommendation that authors can give based on their findings? It would be nice to see it.

Keywords- Line 88, how is epidemiology a keyword when there is no mention of it in the abstract?

Introduction

- Line 99 delete etc. and be specific. You probably have to add dyslipidemia, hypertension and abdominal obesity which are components of metabolic syndrome.

Materials and Methods

- Line 120, should be “Study participants”

- Line 125, sampling or sample?

- Line 127, what was provided electronically?

- Lines 128 to 129, apart from the in-person testing, what was the other way of testing? Please include some details.

- Figure 1, last box, what do you mean by “staring”? It would be nice also to see a box with the number of participants on which the analysis was based for this study.

- The sentence beginning line 148 and ending line 150 should go to the section on ethical considerations. If you don’t have one, please have one and take all the ethical issues there.

- Study variables: authors should state the primary outcome/s (dependent variable) and secondary outcome/s

- Line 156, “Have you smoked more than 100 cigarettes in your entire life?” cite where you obtained this standard. Does this mean that if one smokes more than 100 cigarettes then they have a heightened risk of CVD?

- Lines 157 to 158, I don’t think this is part of the “study variable” but a study procedure “The non-fasting blood samples were drawn at LifeGene test centers”, revise accordingly. I encourage the authors to have a subsection on “Study procedures” separate from the “study variables” so that lines 157 to 163 can go there.

- Authors should have a section for “definitions” e.g the smoking of 100 cigarettes, calculation of BMI and apoB/apoA1 ratio.

- Lines 164 to 166, delete because it has already been stated above (section on study sample)

Results

- Line 184, how many were males and females? Only state the majority.

- I don’t understand why Table 1 was based on sex (male and female), does it mean, the authors were also looking at the sex differences in the outcomes? If not please delete.

- This section can be divided as follows:

o 1. “Characteristics of the study participants”, where you describe the distribution of different study variables, NO need to show the table.

o 2. Table 1 association between ApoA1 and independent variables

o 3. Table 2 do the same for ApoB

o 4. Table 3 do the same for ApoA1/ApoB ratio

o 5. Table 4 do the same for triglycerides

o 6. Table 5 do the same for total cholesterol.

- NOTE: each table should have its own subheading and narrations. All the narrations should be above the table. Narrate the significant findings first.

- All significant findings in the models should be narrated/interpreted.

- Since total cholesterol is part of the outcome, the results should be included in the main text NOT as supplementary.

Discussion

- Line 251, delete the p-value. Do the same for line 257

- The section is well-written

Conclusion.

- The section is well-written

Reviewer #2: The manuscript by Sharma et al “’Associations between birth variables and adult apolipoproteins: The LifeGene Cohort” is interesting and presents original findings that add new information to literature. The sample size is large enough to make valid inferences. The paper can benefit from a few suggestions to further improve it.

Minor

1. This study is a cross-section study using participants from another prospective study (The LifeGene Study). This needs to be clear in the methods of both the abstract and main text

2. Am not sure if the usage of “adult” before “apolipoprotein” is appropriate in the title and abstract. Does adult refer to the type of apolipoproteins (not sure if we do refer to them as such) or the age category of the participant being studied? Consider editing the title/abstract to avoid the confusion. Also, “variables” can be substituted with “characteristics” or another term.

3. It appears birth weight and gestation age are the only birth characteristics referred to and mostly birth weight appears to be central to the study. I would suggest for the title to be more reflective of the main findings. However, this is not major and feel free to ignore

4. The primary outcome variable needs to be specified for the manuscript to be more focused to avoid a fishing expedition type of aim: is it apoA1 or apoB or their ratio? In my opinion, apoB/ApoA1 ratio should be the primary out as it is a better risk marker than individual apolipoproteins under discussion.

5. Abstract lines 82-83. It’s no clear which outcome was not associated with cholesterol/was associated with triglycerides

6. Lines 106-107. The authors themselves have indicated that Multiple factors, including lifestyle, dietary habits, and genetic makeup, influence the serum concentration of apolipoproteins and yet they have not clearly written this in their limitation section for related factors that they did not include in their study but with potential to confound the results

7. Inclusion criteria should be more specific i.e what was the age of inclusion? Adults aged 18 years and above or even children where included? See lines 121 vs 126

8. The flow of the Methods section needs some editing. Please follow reporting guidelines https://www.equator-network.org/ . The strobe checklist is used but reporting ad writing format especially in methods does not clearly indicate the subheadings for proper flow

9. In the results section it’s better to indicate the “n” for each variable and only for variables that had an “n” lower than the actual sample size. In Table 1, the meaning of N (sample)* is not clear

10. What criteria was used to arrive at 1 100 cigarettes? Why not 50 or 200 etc? See table 1

11. Table 2 tittle does not reflect what is in the table. Further the words in the cells /rows are not aligned properly. Consider using a row for each subcategory vs using one row for each variable combined with subcategories

**********

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

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Reviewer #1: No

Reviewer #2: No

**********

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Associations between birth weight and adult apolipoproteins: The LifeGene Cohort

PONE-D-23-17201R1

Dear Dr. Sharma,

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,

Enoch Odame Anto

Academic Editor

PLOS ONE