PONE-D-19-26778

A single nucleotide polymorphism in the HOMER1 gene is associated with sleep latency and theta power in sleep electroencephalogram

PLOS ONE

Dear Prof Pedrazzoli,

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.

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ACADEMIC EDITOR: Please consider the minor concerns highlighted by both reviewers: 

1) Better discuss that the study of only one gene (and one SNP) and the multifactoral phenotypes with possible multiple genetic factors 

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Academic Editor

PLOS ONE

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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: Partly

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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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: In this study, the authors evaluated the association of a specific SNP in the HOMER1 gene with specific aspects of sleep in a representative sample of the Brazilian population. They in fact hypothesize that, given the importance of the glutamatergic system regulating sleep and prolonged wakefulness, genetic variation in the HOMER1 gene might explain inter-individual variability in several sleep traits measured using polysomnography.

Even if they studied only a gene and only one SNP of this gene, the study is well conducted and the sample size of studied subjects is consistent

The research is quite original, the experiments and the statistical analyses were conducted in a proper way and the paper is written in a clear and intelligible way.

Some minor issues are to be considered:

The author should better discuss that this study involve only one gene (and one SNP) but the phenotypes they are discussing is multifactorial and the genetic factors involved can be numerous. The gene they are studying may give a contribution but it does not explain the whole genetic variability of these phenotypes. They should also discuss about the possibility of other SNPs (and HAPLOTYPES) of this gene involved Are already known other SNPs? Could they sequence the entire gene in a group of subjects in order to study this variability and the existence of other SNPs? They should at least discuss it

They should also discuss about the functional role and meaning of the SNP they analyzed

Reviewer #2: In the current manuscript Pedrazzoli et al., examine the association between overnight sleep parameters and a polymorphism in the Homer1 gene in a Brazilian population. The authors report significant genotype interactions in the Homer1 3'UTR and sleep latency, efficiency and other parameters, as well as an interaction with Theta power in the EEG recordings. Recent studies have revealed genetic links with the Homer1 gene and psychiatric conditions. Basic research has also shown an important role for the Homer1 gene in sleep behavior in rodents and insects. The current work is presented in a straight forward manner and the data collection has been done rigorously and appropriately.

Considering the material covered in this manuscript it would be highly appropriate to include in the bibliography a recent high profile paper on the role of Homer1a in synaptic plasticity during sleep. (Diering et al., 2017 Science, PMID: 28154077). This paper shows that Homer1a protein is important to regulate mGluR1/5 signaling during sleep and for sleep-dependent remodeling of synapses. A second paper Holst et al., 2017 eLife, PMID: 28980941 shows that mGluR5 is upregulated during sleep deprivation in humans and is required for appropriate response to sleep deprivation in mice.

I have no other concerns about the current manuscript.

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Reviewer #1: No

Reviewer #2: Yes: Graham Hugh Diering

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A single nucleotide polymorphism in the HOMER1 gene is associated with sleep latency and theta power in sleep electroencephalogram

PONE-D-19-26778R1

Dear Dr. Pedrazzoli,

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.

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Kind regards,

Andrea Romigi, M.D., Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: