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

U. Vosa*, A. Claringbould*, H.J. Westra, M.J. Bonder, P. Deelen, B. Zeng, H. Kirsten, A. Saha, R. Kreuzhuber, S. Yazar, H. Brugge, R. Oelen, D.H. de Vries, M.G.P. van der Wijst, S. Kasela, N. Pervjakova, I. Alves, M.J. Fave, M. Agbessi, M.W. ChristiansenR. Jansen, I. Seppala, L. Tong, A. Teumer, K. Schramm, G. Hemani, J. Verlouw, H. Yaghootkar, R.S. Flitman, A. Brown, V. Kukushkina, A. Kalnapenkis, S. Rueger, E. Porcu, J. Kronberg, J. Kettunen, B. Lee, F.T. Zhang, T. Qi, J.A. Hernandez, W. Arindrarto, F. Beutner, J. Dmitrieva, M. Elansary, B.P. Fairfax, M. Georges, B.T. Heijmans, A.W. Hewitt, BIOS Consortium, i2QTL Consortium, C.D.A. Stehouwer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.
Original languageEnglish
Pages (from-to)1300-1310
Number of pages22
JournalNature Genetics
Issue number9
Early online date2021
Publication statusPublished - Sept 2021


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