Question: Question:IMPUTE2: the p-value of snps in the output gen file is different from the original snp in plink.assoc .
0
gravatar for m338102001
5.1 years ago by
m33810200110
Taiwan
m33810200110 wrote:

hi, 

i use shapeit to do phasing and then inpute2 to generate the gen file.

but after i performing association test to the gen file and finally get a assoc.dosage file, i found that the p-value of original snp (not the imputed snp) is different from the original one (before phasing and impute).

my original plink file is hg19.

here is my comment line:

 

shapeit:

./shapeit --input_bed mygwas.chr1.bed mygwas.chr1.bim mygwas.chr1.fam \

--input-map genetic_map_chr1_combined_b37.txt \

--output-max mygwas.phased.haps mygwas.phased.sample

 

impute2:

./impute2 -use_prephased_g \

-m genetic_map_chr_combined_b37.txt \

-h ALL_1000G_phase1integrated_v3_chr1_impute.hap \

-l ALL_1000G_phase1integrated_v3_chr1_impute.legend \

-known_haps_g mygwas.phased.haps \

int xxx xxx \

Ne xxx \

-o mygwas.gen \

-phase

 

./plink --dosage mygwas.gen format=3 dose=1 skip0=1 skip1=1 noheader --fam mygwas.fam --assoc --out mygwas.imputed.

 

i think the p-value of original SNP in the mygwas.chr1.bed/bim/fam file should be the same with the output mygwas.imputed.assoc.dosage, but the result showed that they are different. and this really confused me.

could everyone tell me how should i fix this problem? really thanks a lot

snp software error • 2.8k views
ADD COMMENTlink modified 5.1 years ago by Maxime Lamontagne2.1k • written 5.1 years ago by m33810200110
1
gravatar for karl.stamm
5.1 years ago by
karl.stamm3.5k
United States
karl.stamm3.5k wrote:

See here for a LOD Score plot along chromosome 1.

http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000260

I tried to link to figure 4, but please scroll to figure 4 or 5 for an example of a likelihood score plotted against genomic location. 

Wouldn't you expect the statistical odds on each SNP to shift when you add more markers?

ADD COMMENTlink modified 5.1 years ago • written 5.1 years ago by karl.stamm3.5k

dear karl.stamm,

thank you for your reply. but, the p-value of SNP is calculated based on the A/T proportion  in samples. let say before imputation, i have SNP A in original data, and after imputation i add SNP B,C,D,E ,but the A/T proportion of SNP A should not be changed, isn't it?

besides, may i ask you additional question that: if the p-value of SNP A have been changed, what is the possible reason for that?

ADD REPLYlink written 5.1 years ago by m33810200110

Firstly the A/T proportion may have changed, you need to double-check that. Depending on the imputation, and calling algorithms. Although I suppose it is very unlikely to have changed, it is possible. What does really change is the knowledge of genetic structure. I don't know what test is computing your p-value, and it sounds like you don't either. If this was a single independent SNP test, then it is directly related to A/T proportion, and no other markers should matter.  The reason I linked the figures of a LOD Score plot, is because most good association tests will make use of local structure and be influenced by nearby markers. You've added information to the system, so of course a test's result should change. Make a plot of the before and the after and please post them for us to see.

ADD REPLYlink written 5.1 years ago by karl.stamm3.5k
0
gravatar for m338102001
5.1 years ago by
m33810200110
Taiwan
m33810200110 wrote:

thank you karl stemm.
i used --assoc command in PLINK to do association test. after imputation, i used the following command to perform association test.
./plink --dosage mygwas.gen format=3 dose=1 skip0=1 skip1=1 noheader --fam mygwas.fam --assoc --out mygwas.imputed.


eg. many SNPs has p-value of 1e-06, but after imputation, it only get 1e-04. (sorry i dont know how to use URL to upload the picture)


is there any possible that shapeit automatically impute missing genotype in my data? if this really a problem,how can i do to prevent it?

ADD COMMENTlink written 5.1 years ago by m33810200110
1

IMPUTE2 can impute missing data. Check if the p-value of SNPs with a call rate of 100% is still the same.

ADD REPLYlink written 5.1 years ago by Maxime Lamontagne2.1k

thank you, now i know the reason of the changing p-value.

so if i don't want impute2 to perform this autoimpute function, how could i do? because i did'nt see any command that could perform this function in the webpage of IMPUTE2.

 

ADD REPLYlink written 5.1 years ago by m33810200110
1

You could replace the post-imputation genotypes with the original. Use PLINK to remove (--exclude) the SNP from your post-Imputation file and add your old genotype with --merge.

ADD REPLYlink written 5.1 years ago by Maxime Lamontagne2.1k

thank you Maxime Lamontangne ^o^

ADD REPLYlink written 5.1 years ago by m33810200110
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