On 2016 Aug 18, Andrew Kewley commented:

Expression of concern over un-interpretable statistics of multiple candidate gene association studies.

The lack of replication of candidate gene association studies has led to much discussion and debate. It is generally considered that each candidate cannot be considered to be an independent hypothesis, hence the alpha level needs to be corrected for multiple comparisons. There is no discussion of this in the paper.

This research group have published multiple candidate gene manuscripts in addition to this study [1,2,3,4] (Most of which are not listed on pub-med), and may have other unpublished data. Hence it is difficult to know what alpha should be used for significance, after correcting for multiple comparisons. If correcting for 678 comparisons, then none of the results reach significance and the overall conclusion should be quite different.

In general, future genetic studies should utilise genome-wide association methodology to avoid such biases.

[1] Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients. Sonya M. Marshall-Gradisnik, Peter Smith, Ekua W. Brenu, Bernd Nilius, Sandra B. Ramos and Donald R. Staines Immunology and Immunogenetics Insights 2015:7 1-6

[2] Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. Marshall-Gradisnik, SM; Chacko, A; Johnston, S; Smith, P; Nilius, B; et al. Immunology and Immunogenetics Insights 8 (2016): 1-2.

[3] Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients. Marshall-Gradisnik, Sonya; Smith, Peter; Nilius, Bernd; Staines, Donald R. Immunology and Immunogenetics Insights 7 (2015): 7-20.

[4] Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. T. K. Huth, E. W. Brenu, D. R. Staines, and S. M. Marshall-Gradisnik. Gene Regulation and Systems Biology 2016:10 43-49

On 2016 Aug 18, Andrew Kewley commented:

Expression of concern over un-interpretable statistics of multiple candidate gene association studies.

The lack of replication of candidate gene association studies has led to much discussion and debate. It is generally considered that each candidate cannot be considered to be an independent hypothesis, hence the alpha level needs to be corrected for multiple comparisons. There is no discussion of this in the paper.

This research group have published multiple candidate gene manuscripts in addition to this study [1,2,3,4] (Most of which are not listed on pub-med), and may have other unpublished data. Hence it is difficult to know what alpha should be used for significance, after correcting for multiple comparisons. If correcting for 678 comparisons, then none of the results reach significance and the overall conclusion should be quite different.

In general, future genetic studies should utilise genome-wide association methodology to avoid such biases.

[1] Examination of Single Nucleotide Polymorphisms (SNPs) in Transient Receptor Potential (TRP) Ion Channels in Chronic Fatigue Syndrome Patients. Sonya M. Marshall-Gradisnik, Peter Smith, Ekua W. Brenu, Bernd Nilius, Sandra B. Ramos and Donald R. Staines Immunology and Immunogenetics Insights 2015:7 1-6

[2] Genotype Frequencies of Transient Receptor Potential Melastatin M3 Ion Channels and Acetylcholine Muscarinic M3 Receptor Gene Polymorphisms in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. Marshall-Gradisnik, SM; Chacko, A; Johnston, S; Smith, P; Nilius, B; et al. Immunology and Immunogenetics Insights 8 (2016): 1-2.

[3] Examination of Single Nucleotide Polymorphisms in Acetylcholine Receptors in Chronic Fatigue Syndrome Patients. Marshall-Gradisnik, Sonya; Smith, Peter; Nilius, Bernd; Staines, Donald R. Immunology and Immunogenetics Insights 7 (2015): 7-20.

[4] Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients. T. K. Huth, E. W. Brenu, D. R. Staines, and S. M. Marshall-Gradisnik. Gene Regulation and Systems Biology 2016:10 43-49