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Chunk #62 — Online Methods — eQTS mapping — Multiple testing correction in trans-eQTL and eQTS mapping

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Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.
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To calculate FDR estimates for trans-eQTLs and eQTS, we compared each P-value from the non-permuted meta-analysis with all P-values from 10 meta-analyzed permutation rounds. We note that this differs from the permutation strategy used in the cis-eQTL analysis, because here we used the P-values from all SNP-gene combinations, not just the smallest P-value for each gene. Nevertheless, the 10,317 SNPs tested for trans-eQTLs contained many linked variants. To establish a conservative FDR estimate, we therefore used the pruned set of 4,586 SNPs to perform a meta-analysis for both the non-permuted and permuted datasets. We derived FDR estimates from these limited meta-analyses by sorting the lists of P-values and determining the proportion of P-values in the non-permuted and permuted datasets for each given P-value in the non-permuted dataset. We then applied these FDR estimates to the trans-eQTL results from all 10,317 genetic trait-associated SNPs. If a specific eQTL from the full set was not tested in the meta-analysis conducted on the pruned set, this eQTL was assigned the higher FDR value corresponding to the next eQTL tested in the pruned set.