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

Détails

Ressource 1Télécharger: 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
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
53
Numéro
9
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.
Pubmed
Web of science
Création de la notice
17/09/2021 16:55
Dernière modification de la notice
23/11/2022 7:13
Données d'usage