Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

BIOS Consortium, i2QTL Consortium

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.

Original languageEnglish
Pages (from-to)1300-1310
Number of pages11
JournalNature genetics
Volume53
Issue number9
DOIs
Publication statusPublished - Sep 2021

Bibliographical note

Publisher Copyright:
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine

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