# Hierarchical models with limma?

I have a dataset with (microarray) gene expression data that was sampled from the same individuals at multiple timepoints. Our exposure is a continuous variable, and because this was an observational study there is no consistent pattern of change in exposure over time (eg. one person's exposure may continuously increase, another's may go up and down, another may have no changes, etc.). The exposure is not expected to have any cumulative effect, so different timepoints within a person do not influence each-other. Our goal is to find genes where expression for the gene is associated with the level of exposure.

We are thinking of analyzing this as a hierarchical model, with timepoints nested within person (so a mixed model with a random effect for person). We will also need to control for a few covariates, some of which will be the same at all timepoints (race, sex) and some of which may change between timepoints (use of particular medications).

Is this something that it is possible to use limma for? I found that limma has a function called duplicateCorrelation() intended for block designs that some people have tried to use to fit mixed models, but I am not sure whether it can be used for this. Or if not limma, then what would you suggest?

• From the help page of duplicateCorrelationEstimate the correlation between duplicate spots (regularly spaced replicate spots on the same array) or between technical replicates from a series of arrays.. So I wouldn't advise to use to account for this effect with this function. – llrs May 2 '18 at 10:01