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

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.

doi:10.1038/s41588-021-00913-z

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

Details

Download: 34475573_BIB_9462F2AB5F22.pdf (3749.08 [Ko])
State: Public
Version: Author's accepted manuscript
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Serval ID

serval:BIB_9462F2AB5F22

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

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

Number

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.

URN

urn:nbn:ch:serval-BIB_9462F2AB5F220

OAI-PMH

oai:serval.unil.ch:BIB_9462F2AB5F22

DOI

10.1038/s41588-021-00913-z

Pubmed

34475573

Web of science

000692073000001

Create date

17/09/2021 17:55