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.

Détails

Télécharger: 34475573_BIB_9462F2AB5F22.pdf (3749.08 [Ko])
Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée

ID Serval

serval:BIB_9462F2AB5F22

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

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

Périodique

Nature genetics

Auteur⸱e⸱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.

Collaborateur⸱rice⸱s

BIOS Consortium, i2QTL Consortium

Contributeur⸱rice⸱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

Statut éditorial

Publié

Date de publication

09/2021

Peer-reviewed

Oui

Volume

Numéro

Pages

1300-1310

Langue

anglais

Notes

Publication types: Journal Article
Publication Status: ppublish

Résumé

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

Création de la notice

17/09/2021 16:55