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closeReferee Comments: Referee 1
Posted by PLOS_ONE_Group on 17 Mar 2008 at 22:43 GMT
Referee 1's Review:
The manuscript by Han et al describes a study on the association between osteopontin (SPP1) and SLE. SPP1 was selected for the study because previously implicated roles for SPP1 in SLE, including previous genetic association studies. The most interesting finding of the study is a suggestive association between SNPs in the SPP1 gene and SLE in male patients. There are few prior studies that have addressed SLE in males. The Discussion-section recognizes that a weakness of the study is the low number of male SLE patients analyzed. Hopefully this study with a potentially interesting finding will stimulate other researchers to replicate the finding in a larger number of male SLE patients.
The manuscript is clearly written in good English. Below are some suggestions for minor improvement of the manuscript.
A surprising number of the SNPs included in the original panel for genotyping turned out to be monomorphic or to have low minor allele frequencies (19 SNPs out of 33). It would be of interest to know according to what criteria the SNPs were selected for genotyping. Was the study conducted a long time ago, when the SNP-databases contained sequencing errors? It would also be of interest to know how much of the genetic variation of the SPP1 gene that is captured by the 11 successfully genotyped SNPs.
The results are presented in four Tables. The number of individuals analyzed should be provided in Table 1 and Table 4, to make it easier for the reader to judge the significance of the results. Table 3 presents verification of the results obtained by logistic regression in Table 2 using GC, STRAT and PCA. The acronyms for the methods should not be used in the heading of Table 3. The numbers presented in Table 3 are not explained, but presumably they are P-values. This should be indicated in the Table. It is inappropriate to provide the p-values with four decimals as is done in Table 3, particularly when the total number of male samples analyzed is in the range of 100.
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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.