Publications
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
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.
| Type | Journal |
|---|---|
| ISBN | 1546-1718 (Electronic) 1061-4036 (Linking) |
| Authors | Vosa, 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.; Fave, M. J.; Agbessi, M.; Christiansen, M. W.; 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, J. A.; Arindrarto, W.; Beutner, F.; Consortium, Bios; i, Q. T. L. Consortium; Dmitrieva, J.; Elansary, M.; Fairfax, B. P.; Georges, M.; Heijmans, B. T.; Hewitt, A. W.; Kahonen, M.; Kim, Y.; Knight, J. C.; Kovacs, P.; Krohn, K.; Li, S.; Loeffler, M.; Marigorta, U. M.; Mei, H.; Momozawa, Y.; Muller-Nurasyid, M.; Nauck, M.; Nivard, M. G.; Penninx, Bwjh; 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.; Tonjes, A.; van Dongen, J.; van Iterson, M.; Veldink, J. H.; Volker, 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.; Lehtimaki, 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. |
| Responsible Garvan Author | Professor Joseph Powell |
| Publisher Name | NATURE GENETICS |
| Published Date | 2021-09-30 |
| Published Volume | 53 |
| Published Issue | 9 |
| Published Pages | 1300-1310 |
| Status | Published in-print |
| DOI | 10.1038/s41588-021-00913-z |
| URL link to publisher's version | https://www.ncbi.nlm.nih.gov/pubmed/34475573 |