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Co-expression analysis reveals interpretable gene modules controlled by trans-acting genetic variants.


ABSTRACT: Understanding the causal processes that contribute to disease onset and progression is essential for developing novel therapies. Although trans-acting expression quantitative trait loci (trans-eQTLs) can directly reveal cellular processes modulated by disease variants, detecting trans-eQTLs remains challenging due to their small effect sizes. Here, we analysed gene expression and genotype data from six blood cell types from 226 to 710 individuals. We used co-expression modules inferred from gene expression data with five methods as traits in trans-eQTL analysis to limit multiple testing and improve interpretability. In addition to replicating three established associations, we discovered a novel trans-eQTL near SLC39A8 regulating a module of metallothionein genes in LPS-stimulated monocytes. Interestingly, this effect was mediated by a transient cis-eQTL present only in early LPS response and lost before the trans effect appeared. Our analyses highlight how co-expression combined with functional enrichment analysis improves the identification and prioritisation of trans-eQTLs when applied to emerging cell-type-specific datasets.

SUBMITTER: Kolberg L 

PROVIDER: S-EPMC7470823 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Co-expression analysis reveals interpretable gene modules controlled by <i>trans</i>-acting genetic variants.

Kolberg Liis L   Kerimov Nurlan N   Peterson Hedi H   Alasoo Kaur K  

eLife 20200903


Understanding the causal processes that contribute to disease onset and progression is essential for developing novel therapies. Although <i>trans</i>-acting expression quantitative trait loci (<i>trans</i>-eQTLs) can directly reveal cellular processes modulated by disease variants, detecting <i>trans</i>-eQTLs remains challenging due to their small effect sizes. Here, we analysed gene expression and genotype data from six blood cell types from 226 to 710 individuals. We used co-expression modul  ...[more]

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2007-01-26 | GSE6848 | GEO