Large-scale cis - and trans -eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Number of Authors: 110 2021 (English) In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, no 9, p. 1300-1310Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages Springer Nature, 2021. Vol. 53, no 9, p. 1300-1310
National Category
Medical Genetics and Genomics
Identifiers URN: urn:nbn:se:ltu:diva-86989 DOI: 10.1038/s41588-021-00913-z ISI: 000692073000001 PubMedID: 34475573 Scopus ID: 2-s2.0-85115732255 OAI: oai:DiVA.org:ltu-86989 DiVA, id: diva2:1591365
Note Godkänd;2021;Nivå 0;2021-09-30 (alebob);
Funder: For funding information, see Acknowledgements https://www.nature.com/articles/s41588-021-00913-z#Ack1
2021-09-062021-09-062025-02-10 Bibliographically approved