[GenABEL-dev] deflated chi2 from ProbABEL output
Yurii Aulchenko
yurii.aulchenko at gmail.com
Thu Jan 6 23:48:06 CET 2011
slides attached
we do not explicitly explain how to do the test in protocols, so I do
not send that
Aaron, can you please outline in short the 'correct' procedure'?
(probably I have that outlined, in which case can you please just
confirm)
Yurii
On Thu, Jan 6, 2011 at 10:48 PM, Yurii Aulchenko
<yurii.aulchenko at gmail.com> wrote:
> Oh mine. You used wrong option - we have had multiple problems using
> the procedure you've outlined. Sorry it was not clear it is bad one...
>
> The interaction covariate you need to include at step 2 (probabel),
> not to polygenic. never use --interaction_only (I actually thought we
> have killed this option, but apparently not - something to do). I will
> send you some slides about that known problem + the latest protocol we
> used for this type of analysis; if you do not get that within a day,
> please remind me.
>
> Yurii
>
> On 1/6/11, Zhai, Guangju <guangju.zhai at kcl.ac.uk> wrote:
>> Hi, Yurii
>>
>> Happy New Year!
>>
>> I managed to complete my interaction analyses but noticed that there is a
>> huge deflated chi2 for the interaction effect, the lambda ranged from 0.175
>> to 0.678 in my four phenotype analyses. There is no problem for the SNP main
>> effect, the lambdas are close to 1 as expected. Can you help explain why?
>>
>> What I did was I first run polygenic model in GenABEL with all covariates
>> included, then run ProbABEL with interaction_only and mmscore function. The
>> following is one of my command line used:
>>
>> ProbABEL/bin/palinear -p z_fev1_interaction_smk_pheno.PHE -i
>> proab_CHR22.machinfo -d 22.gen.dose.fvi --map proab_CHR22.machlegend
>> --mmscore mmscore_z_fev1_InvSigma_aj_smk_ever_smk_currrent_packyr.dat
>> --interaction_only=1 -c 22 --out z_fev1_interaction_smk_chr22
>>
>> Thanks,
>>
>> Guangju
>>
>> -----Original Message-----
>> From: Yurii Aulchenko [mailto:yurii.aulchenko at gmail.com]
>> Sent: 21 December 2010 17:09
>> To: Zhai, Guangju
>> Subject: Re: time to run ProbABEL
>>
>> This is indeed big problem - the running time with mmscore. We work
>> hard on new method (grammar+) which will help a lot. We expect it to
>> be out for use in next month or two.
>>
>> Yurii
>>
>> On 12/21/10, Zhai, Guangju <guangju.zhai at kcl.ac.uk> wrote:
>>> Thanks, Yurii
>>>
>>> In my situation, it looks take much more than 7 days to complete. Given I
>>> run 4 phenotypes, it will take couple of months to complete.
>>>
>>> I don't know what command Dana used, but she has unrelated samples, so it
>>> wouldn't be "mmscore", but with three covariates plus one interaction term
>>> in linear regression model.
>>>
>>> Kind regards
>>> Guangju
>>>
>>> From: yurii.aulchenko at gmail.com [mailto:yurii.aulchenko at gmail.com]
>>> Sent: 21 December 2010 08:48
>>> To: Zhai, Guangju
>>> Subject: Re: time to run ProbABEL
>>>
>>> It is expected that 'mmscore' analysis is taking a while (say, 3000 people
>>> is about 3-7 days to complete). Also, analysis with 3 covariates + SNPxE
>>> interaction is expected to take twice longer then main effects only with 1
>>> covariate.
>>>
>>> Do you know what command/model did Dana use to run analysis?
>>>
>>> Yurii
>>>
>>> On Dec 20, 2010 5:05pm, "Zhai, Guangju" <guangju.zhai at kcl.ac.uk> wrote:
>>>> Hi, Yurii
>>>>
>>>>
>>>>
>>>> I am running my GWAS interaction analysis using ProbABEL, the program
>>>> seems running fine but taking such a substantial time. I have just over
>>>> 3000 related samples, after running polygenic model in GenABEL, I set up
>>>> ProbABEL to run mmscore test last Wed, it has just completed 2 analyses
>>>> on
>>>> chr 1 (I have 4 analyses on each of the 22 chromosomes) by yesterday. It
>>>> looks it will take ages to complete the analyses.
>>>>
>>>>
>>>>
>>>> Today I have a communication with Dana from ARIC study, she used ProbABEL
>>>> to run the same analyses as I am doing in 9000 unrelated individuals, but
>>>> only took her less than a day to complete.
>>>>
>>>>
>>>>
>>>> I have checked my output so far, it seems fine, I didn't find any
>>>> strange
>>>> thing. So wonder if that is kind of what expected or there is something
>>>> that I can do to speed up the analyses? I am using the ProbABEL vesion
>>>> 0.1-9c.
>>>>
>>>>
>>>>
>>>> Thanks,
>>>>
>>>>
>>>>
>>>> Guangju
>>>>
>>>>
>>>>
>>>> -----Original Message-----
>>>>
>>>> From: Yurii Aulchenko [mailto:yurii.aulchenko at gmail.com]
>>>>
>>>> Sent: 16 December 2010 16:25
>>>>
>>>> To: Zhai, Guangju; l.karssen
>>>>
>>>> Subject: Re: impute2mach
>>>>
>>>>
>>>>
>>>> You use version of ProbA which is very old and does not support DatA
>>>> format
>>>>
>>>>
>>>>
>>>> Upgrade to the latest (0.1-9d or so)!
>>>>
>>>>
>>>>
>>>> Yurii
>>>>
>>>>
>>>>
>>>> On 12/16/10, Zhai, Guangju guangju.zhai at kcl.ac.uk> wrote:
>>>>
>>>> > Hi, Yurii
>>>>
>>>> >
>>>>
>>>> > After converting all the files, I tried to run the ProABEL, but got a
>>>>
>>>> > problem which said "segmentation fault", the below is the log file. I
>>>>
>>>> > thought it was a RAM issue, but we got 250GB RAM here, the ProABEL
>>>> > manual
>>>>
>>>> > said it only requires a small RAM. Could you please advise how to sort
>>>> > this
>>>>
>>>> > problem out?
>>>>
>>>> >
>>>>
>>>> > Many thanks,
>>>>
>>>> >
>>>>
>>>> > Guangju
>>>>
>>>> >
>>>>
>>>> > [guangju at dtrcluster interaction-lung]$ ProbABEL/bin/palinear -p
>>>>
>>>> > z_fev1_pheno.PHE -i chr22.machinfo -d 22.gen.dose.fvi --map
>>>> > chr22.machlegend
>>>>
>>>> > --mmscore mmscore_z_fev1_InvSigma_aj_smk_ever_smk_currrent_packyr.dat
>>>>
>>>> > --interaction_only=1 --out z_fev1_interaction_chr22
>>>>
>>>> > ProbABEL v. 0.1-3 (Nov 11, 2009) (C) Yurii Aulchenko, Maksim
>>>> > Struchalin,
>>>>
>>>> > EMCR
>>>>
>>>> >
>>>>
>>>> > Options in effect:
>>>>
>>>> > --pheno = z_fev1_pheno.PHE
>>>>
>>>> > --info = chr22.machinfo
>>>>
>>>> > --dose = 22.gen.dose.fvi
>>>>
>>>> > --ntraits = 1
>>>>
>>>> > --ngpreds = 1
>>>>
>>>> > --interaction = 0
>>>>
>>>> > --interaction_only = 1
>>>>
>>>> > --mmscore =
>>>>
>>>> > mmscore_z_fev1_InvSigma_aj_smk_ever_smk_currrent_packyr.dat
>>>>
>>>> > --map = chr22.machlegend
>>>>
>>>> > --nids = estimated from data
>>>>
>>>> > --chrom = not in output
>>>>
>>>> > --out = z_fev1_interaction_chr22
>>>>
>>>> > --skipd = 2
>>>>
>>>> > --separat = " "
>>>>
>>>> > --score = OFF
>>>>
>>>> > --nohead = OFF
>>>>
>>>> > --allcov = OFF
>>>>
>>>> > --robust = OFF
>>>>
>>>> > Number of SNPs = 40322
>>>>
>>>> > Actual number of people in phenofile = 5654; using all of these
>>>>
>>>> > model is running without smk_ever, term
>>>>
>>>> > Linear model: ( z_fev1 ) ~ mu + smk_ever + smk_current + packyr +
>>>> > SNP_A1
>>>> > +
>>>>
>>>> > smk_ever*SNP_A1
>>>>
>>>> > you are runing mmscore...
>>>>
>>>> > Reading data ...Segmentation fault
>>>>
>>>> >
>>>>
>>>> > -----Original Message-----
>>>>
>>>> > From: Yurii Aulchenko [mailto:yurii.aulchenko at gmail.com]
>>>>
>>>> > Sent: 18 November 2010 18:25
>>>>
>>>> > To: Zhai, Guangju; l.karssen
>>>>
>>>> > Subject: Re: impute2mach
>>>>
>>>> >
>>>>
>>>> >> By the way, how the generated .fvd and .fvi be used in the ProABEL?
>>>>
>>>> >
>>>>
>>>> > the same way you do that with regulat files -- if the program sees
>>>>
>>>> > that you specify *fvi as geno/dose file, it will know this DA data.
>>>>
>>>> > Should be described in PA manual
>>>>
>>>> >
>>>>
>>>> > Yurii
>>>>
>>>> >
>>>>
>>>> >> -----Original Message-----
>>>>
>>>> >> From: Yurii Aulchenko [mailto:yurii.aulchenko at gmail.com]
>>>>
>>>> >> Sent: 18 November 2010 17:25
>>>>
>>>> >> To: Zhai, Guangju; Stepan Yakovenko; Message Logger
>>>>
>>>> >> Subject: Re: impute2mach
>>>>
>>>> >>
>>>>
>>>> >> Ok, great news! Stepan, thanks for doing this work!
>>>>
>>>> >>
>>>>
>>>> >> Zhai, I think by now you are a kind of expert in issues which may go
>>>>
>>>> >> wrong with impute2* procedures :) In the future, if we get people with
>>>>
>>>> >> similar problems arising, would that be ok to involve you into
>>>>
>>>> >> dicussion so you can provide an advise based on your experience?
>>>>
>>>> >>
>>>>
>>>> >> Best wishes,
>>>>
>>>> >> Yurii
>>>>
>>>> >>
>>>>
>>>> >> On 11/18/10, Zhai, Guangju guangju.zhai at kcl.ac.uk> wrote:
>>>>
>>>> >>> It looks yes! At least on chr 22 data.
>>>>
>>>> >>>
>>>>
>>>> >>> I will keep you updated for other chrs.
>>>>
>>>> >>>
>>>>
>>>> >>> Many thanks for both you and Stepan!!
>>>>
>>>> >>>
>>>>
>>>> >>>
>>>>
>>>> >>> Guangju
>>>>
>>>> >>>
>>>>
>>>> >>> -----Original Message-----
>>>>
>>>> >>> From: Yurii Aulchenko [mailto:yurii.aulchenko at gmail.com]
>>>>
>>>> >>> Sent: 18 November 2010 12:45
>>>>
>>>> >>> To: Zhai, Guangju; Stepan Yakovenko; Message Logger
>>>>
>>>> >>> Subject: Re: impute2mach
>>>>
>>>> >>>
>>>>
>>>> >>> Loss of precision -- no problem with that, expected and appreciated
>>>>
>>>> >>> behaviour\
>>>>
>>>> >>>
>>>>
>>>> >>> So, is the problem fixed at the end?!
>>>>
>>>> >>>
>>>>
>>>> >>> On Thu, Nov 18, 2010 at 1:41 PM, Zhai, Guangju
>>>> >>> guangju.zhai at kcl.ac.uk>
>>>>
>>>> >>> wrote:
>>>>
>>>> >>>> Hi, Stepan
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>> I just tested after adding two missing columns in the first two
>>>> >>>> lines
>>>> >>>> in
>>>>
>>>> >>>> the
>>>>
>>>> >>>> sample file and adding the headers in the info file, it seems fine,
>>>> >>>> no
>>>>
>>>> >>>> warning appeared! But I still have the following statement: not sure
>>>>
>>>> >>>> what
>>>>
>>>> >>>> that mean and if it has impact on the generated files?
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>> Guangju
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>>
>>>>
>>>> >>>> Loss of precision / loss of data during conversion from DOUBLE to
>>>> >>>> FLOAT.
>>>>
>>>> >>>>
>>>>
>>>> >>>> Futher conversion warnings omitted.
>>>>
>>>> >>>
>>>>
>>>> >>
>>>>
>>>> >> --
>>>>
>>>> >> Sent from my mobile device
>>>>
>>>> >>
>>>>
>>>> >
>>>>
>>>>
>>>>
>>>> --
>>>>
>>>> Sent from my mobile device
>>>>
>>>
>>
>> --
>> Sent from my mobile device
>>
>
> --
> Sent from my mobile device
>
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