Frequency of HLA Alleles in a Cohort of 100 Romanian Late-Life Adults: An Academic Insight into Genetic Longevity

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

108 - a more detailed description of the patient group should be provided, as this may affect the change in allele frequencies. This includes donors. 130 - It is better to provide comparative figures for long-lived individuals and young individuals together on a single diagram. The number of figures should be reduced. A single table for all loci should be provided in the Appendix, as this will make it easier to read. 237 - the differences between the data should be explained. This may be due to the different resolutions used in the studies. The Discussion section should be expanded. Include data on the functional association of the found alleles (protective effect against a certain disease, etc.).

Author Response

108 - a more detailed description of the patient group should be provided, as this may affect the change in allele frequencies. This includes donors.

I did a slightly more detailed description of the patient groups.

30 - It is better to provide comparative figures for long-lived individuals and young individuals together on a single diagram. The number of figures should be reduced. A single table for all loci should be provided in the Appendix, as this will make it easier to read.

I rethinked the figures and tables. The results for elderly and young individuals are compared in the Table A1 and A2 in Appendix. I introduced comparative diagrams for long-lived women and men. Comparative diagrams of old vs young was to difficult since they don't share many alleles.

237 - the differences between the data should be explained. This may be due to the different resolutions used in the studies. The Discussion section should be expanded. Include data on the functional association of the found alleles (protective effect against a certain disease, etc.).

I expanded the discussion section with mentions of protective and susceptible alleles. The reasons why our results are different are mentioned. The two main reasons are the resolution (high res vs low res) and cohort size.

I also included a new reference, a study on protective and susceptible HLA alleles.

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript's high-resolution HLA dataset is a valuable resource, but the paper requires major revision. The text is extremely repetitive, and the data is presented redundantly. To support its claims about longevity, the authors must perform and discuss the missing statistical analyses. I suggest focusing on three key questions: 1) What are the significant allele frequency differences between the elderly and young cohorts? 2) Are there sex-specific differences in allele frequencies? 3) How do frequencies change when stratifying the broad 65-90 age group (e.g., by decade) to better understand longevity-associated differences? Addressing these points and drastically reducing repetitive text are essential.

Author Response

This manuscript's high-resolution HLA dataset is a valuable resource, but the paper requires major revision. The text is extremely repetitive, and the data is presented redundantly. To support its claims about longevity, the authors must perform and discuss the missing statistical analyses. I suggest focusing on three key questions: 1) What are the significant allele frequency differences between the elderly and young cohorts? 2) Are there sex-specific differences in allele frequencies? 3) How do frequencies change when stratifying the broad 65-90 age group (e.g., by decade) to better understand longevity-associated differences? Addressing these points and drastically reducing repetitive text are essential.

You are correct. I rethinked the figures and tables. All the results for both elderly and young inviduals are found in Table A1 and A2 in Appendix. We did a sex-specific analysis with figures for each locus that compares the results for men and women. We only did the age group stratification analisys fot he HLA class I alleles (HLA-A, B and C).

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed my previous comments. With these revisions, I consider the manuscript suitable for publication.