--cojo-slct not selecting the SNP with lowest p-value

ape4fld
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Posts: 1

--cojo-slct not selecting the SNP with lowest p-value Jul 3, 2020 13:00:38 GMT

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Post by ape4fld on Jul 3, 2020 13:00:38 GMT

Hello,

I am running --cojo-slct on separate chromosomes, and noticed that in my output I have a few independent signals in one locus, but none of them are the SNP which has the lowest p-value in that locus (also it is not in the badsnps file). Isn't the SNP with the lowest p-value picked first and then condition for it, and select the next one, etc.?

This are the commands I am using:
gcta64 --bfile file --cojo-slct --cojo-p 5e-8 --maf 0.01 --chr 1 --cojo-file sumstats.txt --out results-cojo

Thanks for any insights into this!

ax
New Member

Posts: 27

--cojo-slct not selecting the SNP with lowest p-value Jul 6, 2020 4:28:42 GMT

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Post by ax on Jul 6, 2020 4:28:42 GMT

Hi ape4fld,

COJO output the SNPs whose p-value is less than 5e-8 in the joint model. So if the SNP with the lowest p-value did not pass the 5e-8 threshold it won't show up in the results file.

It'd be better if you could provide the results table and log file.

Cheers,
AX

currant
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Posts: 1

--cojo-slct not selecting the SNP with lowest p-value Apr 13, 2021 16:23:54 GMT

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Post by currant on Apr 13, 2021 16:23:54 GMT

Hi,

I am running into the same issue when running cojo. My SNP with the smallest p-value definitely passes the significance threshold but is not being selected. Any advice would be amazing, thanks!

waddington
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Posts: 1

--cojo-slct not selecting the SNP with lowest p-value Nov 12, 2021 15:12:12 GMT

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Post by waddington on Nov 12, 2021 15:12:12 GMT

I have run into this exact problem. I think the cause is that OR, BETA, or SE in the sumstats file is not stored with sufficient precision so that for instance 2*pnorm(log(OR)/SE, lower.tail=F) != P. In some sumstats output the SE column for example might be rounded to only 4 digits. If a larger P-value SNP has a slightly larger effect size than the smallest p-value SNP but the standard errors round to the same value, then the larger effect size SNP would be chosen

--cojo-slct seems to be getting the P-value of each SNP by re-calculating it from the b and se columns rather than taking it from the p column. This can be checked by looking at the P column in the cojo.jma and cojo.cma files: they do not match the inputted P-values but they do equal 2*pnorm(b/se, lower.tail=F)

The solution I've found is to calculate a more exact value for the se column in the input file based on the effect size and original p-value, e.g. se=log(OR)/qnorm(P/2, lower.tail=F).

Last Edit: Nov 12, 2021 15:13:58 GMT by waddington