University of Tasmania

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

journal contribution
posted on 2023-05-21, 13:04 authored by Vosa, U, Claringbould, A, Westra, HJ, Bonder, MJ, Deelen, P, Zeng, B, Kirsten, H, Saha, A, Kreuzhuber, R, Yazar, S, Brugge, H, Oelen, R, de Vries, DH, van der Wijst, MGP, Kasela, S, Pervjakova, N, Alves, I, Favve, MJ, Agbessi, M, Christiansen, MW, Jansen, R, Seppala, I, Tong, L, Teumer, A, Schramm, K, Hemani, G, Verlouw, J, Yaghootkar, H, Sonmez Flitman, R, Brown, A, Kukushkina, V, Kalnapenkis, A, Rueger, S, Porcu, E, Kronberg, J, Kettunen, J, Lee, B, Zhang, F, Qi, T, Hernandez, JA, Arindrarto, W, Beutner, F, Dmitrieva, J, Elansary, M, Fairfax, BP, Georges, M, Alexander HewittAlexander Hewitt, Heijmans, BT, Kahonen, M, Kim, Y, Knight, JC, Kovacs, P, Krohn, K, Li, S, Loeffler, M, Marigorta, UM, Mei, H, Momozawa, Y, Muller-Nurasyid, M, Nauck, M, Nivard, MG, Penninx, BWJH, Pritchard, JK, Raitakari, OT, Rotzschke, O, Slagboom, EP, Stehouwer, CDA, Stumvoll, M, Sullivan, P, 't Hoen, PAC, Thiery, J, Tonjes, A, van Dongen, J, van Iterson, M, Veldink, JH, Volker, U, Warmerdam, R, Wijmenga, C, Swertz, M, Andiappan, A, Montgomery, GW, Ripatti, S, Perola, M, Kutalik, Z, Dermitzakis, E, Bergmann, S, Frayling, T, van Meurs, J, Prokisch, H, Ahsan, H, Pierce, BL, Lehtimaki, T, Boomsma, DI, Psaty, BM, Gharib, SA, Awadalla, P, Milani, L, Ouwehand, WH, Downes, K
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.


Publication title

Nature genetics










Menzies Institute for Medical Research



Place of publication

New York

Repository Status

  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions