I have run moderation analysis to study the interaction between SNP (dominant model) of a gene (A) with DNA methylation on cognition measures. For this, I have calculated the mean DNA methylation levels at 3 gene loci: Upstream of TSS (transcriptional start site), promoter, and gene body.

The protein from this gene improves cognition so we expect that increasing serum protein leads to better cognition outcomes. Prior research suggests that methylation in the gene body generally results in increased gene expression.

The results of the analysis showed that: in the carriers of genotype TT, increasing methylation rate in the gene body results in less recognition ability while in the holders of the C allele, higher methylation in the gene body is associated with improved recognition (2 different directions).

I know that different alleles can impact methylation rate but here the direction is completely opposite. How can I interpret the result?

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    $\begingroup$ The addition of a methyl group (groups) can activate or repress genes, do you have a reference that the expected result in this case is activation? $\endgroup$ Commented Apr 26, 2022 at 15:31
  • $\begingroup$ No, I do not have any data about the gene expression or serum protein level. $\endgroup$
    – Mehad
    Commented Apr 27, 2022 at 4:54
  • $\begingroup$ Can you refer to any data in general talking about gene body methylation's effect on gene expression? My feeling was that the effect was somewhat ambiguous and context dependent, but I'm not an expert. Especially in the absence of actual gene expression level for your gene of interest, it's hard to draw conclusions. Additionally, "the protein from this gene improves cognition..." sounds like a pretty squishy result. Cognition is a hard phenotype to measure usually. How large are the effects +/- error of the protein on cognition? What are the effect sizes / errors of alleles on cognition? $\endgroup$ Commented Apr 27, 2022 at 5:39
  • $\begingroup$ Thank you all. Why do you judge me? I am talking about the data I have obtained by analysis. They are not my personal idea! Still, I have not shown them to my supervisors. I wanted to improve my information before that meeting. $\endgroup$
    – Mehad
    Commented Apr 28, 2022 at 2:37
  • $\begingroup$ Fair enough. I apologise. We worry about presenting information to people that might harm anyone, it is a concern on many sites on the network. For example Worldbuilding often gets questions about making explosives or poisons which creates concern. I'll delete those comments. $\endgroup$ Commented Apr 28, 2022 at 3:32


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