TREML2 Gene Expression and Its Missense Variant rs3747742 Associate with White Matter Hyperintensity Volume and Alzheimer’s Disease-Related Brain Atrophy in the General Population
, Stefan Frenzel 1, Alexander Teumer 2, Katharina Wittfeld 1,3, Linda Garvert 1, Antoine Weihs 1, Georg Homuth 4, Holger Prokisch 5,6, Robin Bülow 7, Matthias Nauck 8,9, Uwe Völker 4,9, Henry Völzke 2,9, Hans Jörgen Grabe 1,3,†and Sandra Van der Auwera 1,3,*,†
Round 1
Reviewer 1 Report
This is a very interesting manuscript. The research is on Potential role of the TREML2 in AD. The paper is original. It add New knowledge to this area. It is well written and easy to read. The conclusions consistent with the evidence and arguments presented. The authors address the main question posed. I do not have any comments and I suggest accepting it as it is.
Author Response
We thank Reviewer 1 for the evaluation of our manuscript. As no adjustments were required or suggested by this reviewer, there was nothing to address.
Reviewer 2 Report
Interesting observations on a large population sample. But there are several questions.
1. AD score. The sample is population-based, given its age, with a very small proportion of patients with AD. In this regard, more detailed descriptions of the distribution of the values ​​of this score in the sample and a comparison of the average value of the score for the population sample and the sample of patients with AD are needed. It is possible that the results of the authors are explained by the very low level of AD score in this sample. The authors mention this in the article - it is not necessary to articulate this feature of the sample more clearly.
2. The authors performed a regression analysis and presented the data as an effect size with its reliability. At the same time, real primary data are insufficiently presented - for example, what is the level of expression (median and quartiles) of the gene under study in your sample? Yes, there is table 1 - and it is she who raises questions. Is the gene expression really distributed in such a normal way?
3. According to this table, the level of gene expression is highly stable - with much less stability of the WMH or AD score. And it does not depend on age at all - after all, the variability in age is also very significant.
4. Reference 53 - and that is why it is necessary to expand the description of methods of analysis of expression with a more complete description of how the main effects influencing the assessment of the level of expression in this particular case were taken into account.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
