qval vs pval_beta in *.egenes.txt.gz and *.signif_variant_gene_pairs.txt.gz

[char4816]

Hi,

First off, thank you for all of the awesome work with GTEx v8. I am trying to compare my eQTL results to the v8 GTEx database (see which eQTLs are replicated vs novel to my cell type).

I am thinking it would be optimal for me to compare my eQTLs with q-value < 0.05 to the *.signif_variant_gene_pairs.txt.gz files, however, am struggling to find (or derive) q-values for each of these variant-gene pairs in GTEx:
https://gtexportal.org/home/datasets

As I understand the documentation from:
https://storage.googleapis.com/gtex_analysis_v8/single_tissue_qtl_data/README_eQTL_v8.txt
the order of p-value adjustment follows the path of:
pval_nominal -> pval_perm -> pval_beta -> qval

In the files I see:

• The *.allpairs.txt.gz files only contain pval_nominal.
• The *.signif_variant_gene_pairs.txt.gz files contain adjustments through pval_beta. Since pval_beta tends to exceed 0.05 in these files, I assume that this list of "significant variant-gene pairs" was the subset of *.allpairs.txt.gz with 'qval' ≤ 0.05, however, there is no qval column?
• The *.egenes.txt.gz files contain adjustments through qval.

I am confused as to why qval isn't included in all 3 file types. Given that the "eGenes are the rows with qval ≤ 0.05," I assume I should be using qval to identify which eQTLs replicate between my analysis and GTEx. It would be really helpful if the *.allpairs.txt.gz files contained a qval column for this comparison (or code for which I could derive the qval column?). At first I tried to do qvalue(pval_beta) for the subset of significant variant-gene pairs, but this fails to replicate the qval values since it is a subset of the variant-gene pairs.

Thanks in advance for any help you might be able to provide,
Chris

[francois-a]

Hi,

FDR was computed at the gene level (to identify eGenes), and therefore the q-values are only present in the *.egenes.txt.gz files. For details, please see Section 4.2 of the supplementary materials for additional details.
The *.signif_variant_gene_pairs.txt.gz files contain all pairs that pass the significance threshold for each eGene.

To test replication, consider computing the pi1 statistic (Section 5 of the supplementary materials). For that, you only need the nominal p-values (from the *.allpairs.txt.gz files) in GTEx corresponding to the variant-gene pairs that you're testing for replication.

[char4816]

Francois,

Thank you very much for your helpful reply. This clarifies many of the things I was confused about. I will give this a try and let you know if I get stuck.

Chris