[GenABEL-dev] ProbABEL: mmscore and interaction

[L.C. Karssen]

Hi Nicola,


On 18-10-14 07:58, Pirastu Nicola wrote:
> 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.
> 

Ah, robust SEs... I don't remember of the top of my head if we allow
that option together with mmscore. I'll have a look.


Thanks,

Lennart.

> 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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>>
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-- 
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L.C. Karssen
Utrecht
The Netherlands

lennart at karssen.org
http://blog.karssen.org
GPG key ID: A88F554A
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