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Võsa, U.* ; Claringbould, A.* ; Westra, H.J.* ; Bonder, M.J.* ; Deelen, P.* ; Zeng, B.* ; Kirsten, H.* ; Saha, A.* ; Kreuzhuber, R.* ; Yazar, S.* ; Brugge, H.* ; Oelen, R.* ; de Vries, D.H.* ; van der Wijst, M.G.P.* ; Kasela, S.* ; Pervjakova, N.* ; Alves, I.* ; Favé, M.J.* ; Agbessi, M.* ; Christiansen, M.W.* ; Jansen, R.* ; Seppälä, I.* ; Tong, L.* ; Teumer, A.* ; Schramm, K. ; Hemani, G.* ; Verlouw, J.* ; Yaghootkar, H.* ; Sönmez Flitman, R.* ; Brown, A.* ; Kukushkina, V.* ; Kalnapenkis, A.* ; Rüeger, S.* ; Porcu, E.* ; Kronberg, J.* ; Kettunen, J.* ; Lee, B.* ; Zhang, F.* ; Qi, T.* ; Hernandez, J.A.* ; Arindrarto, W.* ; Beutner, F.* ; BIOS Consortium* ; i2QTL Consortium* ; Dmitrieva, J.* ; Elansary, M.* ; Fairfax, B.P.* ; Georges, M.* ; Heijmans, B.T.* ; Hewitt, A.W.* ; Kähönen, M.* ; Kim, Y.* ; Knight, J.C.* ; Kovacs, P.* ; Krohn, K.* ; Li, S.* ; Loeffler, M.* ; Marigorta, U.M.* ; Mei, H.* ; Momozawa, Y.* ; Müller-Nurasyid, M. ; Nauck, M.* ; Nivard, M.G.* ; Penninx, B.W.J.H.* ; Pritchard, J.K.* ; Raitakari, O.T.* ; Rotzschke, O.* ; Slagboom, E.P.* ; Stehouwer, C.D.A.* ; Stumvoll, M.* ; Sullivan, P.* ; 't Hoen, P.A.C.* ; Thiery, J.* ; Tönjes, A.* ; van Dongen, J.* ; van Iterson, M.* ; Veldink, J.H.* ; Völker, U.* ; Warmerdam, R.* ; Wijmenga, C.* ; Swertz, M.* ; Andiappan, A.* ; Montgomery, G.W.* ; Ripatti, S.* ; Perola, M.* ; Kutalik, Z.* ; Dermitzakis, E.* ; Bergmann, S.* ; Frayling, T.* ; van Meurs, J.* ; Prokisch, H. ; Ahsan, H.* ; Pierce, B.L.* ; Lehtimäki, T.* ; Boomsma, D.I.* ; Psaty, B.M.* ; Gharib, S.A.* ; Awadalla, P.* ; Milani, L.* ; Ouwehand, W.H.* ; Downes, K.* ; Stegle, O.* ; Battle, A.* ; Visscher, P.M.* ; Yang, J.* ; Scholz, M.* ; Powell, J.* ; Gibson, G.* ; Esko, T.* ; Franke, L.*

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

Nat. Genet. 53, 1300-1310 (2021)
Postprint DOI PMC
Open Access Green
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide Association; Serine Biosynthesis; Human Transcriptome; Architecture; Disease; Deficiency; Relevance; Disorder; Links; Risk
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 53, Issue: 9, Pages: 1300-1310 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Institute of Genetic Epidemiology (IGE)
Grants Estonian Research Council grant PRG
ERC under the European Union's Horizon 2020 research and innovation program
Diabetes UK RD Lawrence fellowship
Jacobs Foundation research fellowship
European Research Council (ERC)
VIDI grant
VICI grant from the Netherlands Organisation for Scientific Research (NWO)
European Regional Development Fund
program Mobilitas Pluss
Netherlands Organisation for Health Research and Development
VENI grant from the NWO
NIH
Nederlandse Organisatie voor Wetenschappelijk onderzoek
Sigrid Juselius Foundation
UK MRC
University of Bristol
Swiss National Science Foundation
CHARGE infrastructure
German Federal Ministry of Education and Research (BMBF)
LIFE (Leipzig Research Center for Civilization Diseases), Universitat Leipzig
European Union
Free State of Saxony
KNAW Academy Professor Award
Spinozapremie
Academy of Finland
Novo Nordisk Foundation
Academy of Finland Centre of Excellence in Complex Disease Genetics
EU Horizon 2020
Excellence of Science (FNRS)
FWO
BBMRI-NL (Biobanking and Biomolecular Resources Research Infrastructure)
NWO