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

Details

Serval ID
serval:BIB_9462F2AB5F22
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.
Journal
Nature genetics
Author(s)
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 MGP, 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., 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 BWJH, Pritchard J.K., Raitakari O.T., Rotzschke O., Slagboom E.P., Stehouwer CDA, Stumvoll M., Sullivan P., 't Hoen PAC, 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.
Working group(s)
BIOS Consortium, i2QTL Consortium
Contributor(s)
't Hoen PAC, van Meurs J., van Dongen J., van Iterson M., Swertz M.A., Jan Bonder M.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Publication state
Published
Issued date
09/2021
Peer-reviewed
Oui
Volume
53
Number
9
Pages
1300-1310
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Pubmed
Web of science
Create date
17/09/2021 16:55
Last modification date
24/09/2021 5:39
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