학술논문
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Document Type
Article
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; 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; Fairfax, Benjamin P.; Georges, Michel; 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; Battle, Alexis; Visscher, Peter M.; Yang, Jian; Scholz, Markus; Powell, Joseph; Gibson, Greg; Esko, Tõnu; Franke, Lude
Source
Nature Genetics; 20210101, Issue: Preprints p1-11, 11p
Subject
Language
ISSN
10614036; 15461718
Abstract
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.