[GenABEL-dev] ProbABEL: mmscore and interaction

[Pirastu Nicola]

Hi,

I’ve come up with this in the past before and the main problem with ProbABEL and interactions is that you should use the “robust” standard errors with mmscore which is not possible with ProbABEL. This leads from what I’ve seen to a lot of p-value inflation and as Maksim was saying a lot of false positives. In the end we had to use MixABEL which deals correctly with this. You may want to update ProbABEL in this sense.

Best.

Nicola


Il giorno 18/ott/2014, alle ore 03:13, Maksim Struchalin <m.v.struchalin at mail.ru<mailto:m.v.struchalin at mail.ru>> ha scritto:

Hi Lennart,

If ProbABEL is using the same 'two steps score test' as it was in the first version (section 'Two-step score test for association' in ProbABEL paper http://www.biomedcentral.com/1471-2105/11/134) then, I guess, the GxE term can be included in the model and run in mmscore. It only should be assured that the interaction term goes to the second step (run the model trait_residuals ~ snp + snp*E in mmscore). Otherwise, it may results in false positives.

Actually, in the first paragraph of section 'Two-step score test for association' of ProbABEL paper, it is written that "design matrix may include not only the main SNP effect, but e.g. SNP by environment interaction terms". So, I would include it and look what will happen.

P.S. IMHO it is interesting to run this scenario briefly in a small simulation study.

Best,
Maksim



On 17/10/2014 21:54, L.C. Karssen wrote:

Dear list,

There is a question on the forum [1] that I'm not sure how to answer.
The user wants to run mmscore and test for interactions. There is
nothing in ProbABEL that prevents her from doing that. However, in the
manual we state:

"Though technically --mmscore allows for inclusion of multiple
covariates, these should be kept to minimum as this is a score test. We
suggest that any covariates explaining an essential proportion of
variance should be fit as part of GenABEL’s polygenic procedure."

Does this also apply for interactions between SNP and a covariate? If so
we should produce an error message when both options are specified.


What is the proper way to deal with interactions and mmscore?


Best,

Lennart.


[1] http://forum.genabel.org/viewtopic.php?f=10&t=896




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