gravatar for calen.p.ryan

3 hours ago by

I am running regressions using limma on 450k array DNA methylation data.

I'm interested in the relationship between circulating levels of a hormone and DNAm in ~144,000 CpG sites I've preselected based on variability (non variable sites likely won't tell us anything about our variable of interest).

I run regressions using limma, and plot the p-values, but they don't look uniform at all. The odd thing is that this is exactly the same for all 3 hormone measurements. I tried to remove covariates in case there is collinearity going on, many different versions of these models look exactly the same.

weird_pval_dist

or here if that link isn't working.
weird-uniform

What would explain this kind of distribution - sparse at high and low p-values, but uniform across the rest?

Is there some way I can 'fix' this? More robust tests I can run etc. to see if there is a relationship between my hormones and DNAm?



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