Article (Scientific journals)
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.
Võsa, Urmo; Claringbould, Annique; Westra, Harm-Jan et al.
2021In Nature Genetics, 53 (9), p. 1300-1310
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Keywords :
Blood Proteins/genetics; Gene Expression Regulation/genetics; Genome-Wide Association Study; Humans; Multifactorial Inheritance/genetics; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; Transcriptome/genetics
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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Võsa, Urmo
Claringbould, Annique
Westra, Harm-Jan
Bonder, Marc Jan
Deelen, Patrick
Zeng, Biao
Kirsten, Holger
Saha, Ashis
Kreuzhuber, Roman
Yazar, Seyhan
Brugge, Harm
Battle, Alexis
Visscher, Peter M.
Yang, Jian
Scholz, Markus
Powell, Joseph
Gibson, Greg
Esko, Tõnu
Franke, Lude
Oelen, Roy
de Vries, Dylan H.
van der Wijst, Monique G. P.
Kasela, Silva
Pervjakova, Natalia
Alves, Isabel
Favé, Marie-Julie
Agbessi, Mawussé
Christiansen, Mark W.
Jansen, Rick
Seppälä, Ilkka
Tong, Lin
Teumer, Alexander
Schramm, Katharina
Hemani, Gibran
Verlouw, Joost
Yaghootkar, Hanieh
Sönmez Flitman, Reyhan
Brown, Andrew
Kukushkina, Viktorija
Kalnapenkis, Anette
Rüeger, Sina
Porcu, Eleonora
Kronberg, Jaanika
Kettunen, Johannes
Lee, Bernett
Zhang, Futao
Qi, Ting
Hernandez, Jose Alquicira
Arindrarto, Wibowo
Beutner, Frank
Dmitrieva, Julia
Elansary, Mahmoud ;  Université de Liège - ULiège > GIGA
Fairfax, Benjamin P.
Georges, Michel  ;  Université de Liège - ULiège > Dpt. de gestion vétérinaire des Ressources Animales (DRA) > Génomique animale
Heijmans, Bastiaan T.
Hewitt, Alex W.
Kähönen, Mika
Kim, Yungil
Knight, Julian C.
Kovacs, Peter
Krohn, Knut
Li, Shuang
Loeffler, Markus
Marigorta, Urko M.
Mei, Hailang
Momozawa, Yukihide
Müller-Nurasyid, Martina
Nauck, Matthias
Nivard, Michel G.
Penninx, Brenda W. J. H.
Pritchard, Jonathan K.
Raitakari, Olli T.
Rotzschke, Olaf
Slagboom, Eline P.
Stehouwer, Coen D. A.
Stumvoll, Michael
Sullivan, Patrick
't Hoen, Peter A. C.
Thiery, Joachim
Tönjes, Anke
van Dongen, Jenny
van Iterson, Maarten
Veldink, Jan H.
Völker, Uwe
Warmerdam, Robert
Wijmenga, Cisca
Swertz, Morris
Andiappan, Anand
Montgomery, Grant W.
Ripatti, Samuli
Perola, Markus
Kutalik, Zoltan
Dermitzakis, Emmanouil
Bergmann, Sven
Frayling, Timothy
van Meurs, Joyce
Prokisch, Holger
Ahsan, Habibul
Pierce, Brandon L.
Lehtimäki, Terho
Boomsma, Dorret I.
Psaty, Bruce M.
Gharib, Sina A.
Awadalla, Philip
Milani, Lili
Ouwehand, Willem H.
Downes, Kate
Stegle, Oliver
More authors (98 more) Less
Language :
English
Title :
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.
Publication date :
2021
Journal title :
Nature Genetics
ISSN :
1061-4036
eISSN :
1546-1718
Publisher :
Nature Publishing Group, United Kingdom
Volume :
53
Issue :
9
Pages :
1300-1310
Peer reviewed :
Peer Reviewed verified by ORBi
European Projects :
H2020 - 733100 - SYSCID - A Systems medicine approach to chronic inflammatory disease
Funders :
CE - Commission Européenne [BE]
Commentary :
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
Available on ORBi :
since 19 November 2021

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