[BioC] Odd contrast; does it make statistical sense?

[Ryan C. Thompson]

Hi all,

I'm currently using edgeR to test a somewhat odd contrast. Basically, I 
have multiple groups, and I want to combine them into just 2 big groups 
and test whether the two big groups have significantly different 
averages. I'll give a toy example that demonstrates the same concept. In 
this example, there are 4 groups, A through D, each containing 3 
samples, and I want to test whether the mean of all samples in A & B is 
different from the mean of all samples in C & D:

group <- rep(LETTERS[1:4], 3)
design <- model.matrix(~0+group)
colnames(design) <- LETTERS[1:4]
cont <- makeContrasts((A+B)/2 - (C+D)/2, levels=design)

My worry is that with this contrast, I'm effectively just testing two 
groups against each other, and by having 4 groups in the design I will 
be estimating dispersions that are not appropriate for the test that I'm 
doing, and hence I will overstate my confidence. Or, to put it another 
way, am I doing something equivalent to testing a main effect in a model 
where an interaction term is present?

Thank you,

-Ryan Thompson