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


Vosa, U and Claringbould, A and Westra, HJ and Bonder, MJ and Deelen, P and Zeng, B and Kirsten, H and Saha, A and Kreuzhuber, R and Yazar, S and Brugge, H and Oelen, R and de Vries, DH and van der Wijst, MGP and Kasela, S and Pervjakova, N and Alves, I and Favve, MJ and Agbessi, M and Christiansen, MW and Jansen, R and Seppala, I and Tong, L and Teumer, A and Schramm, K and Hemani, G and Verlouw, J and Yaghootkar, H and Sonmez Flitman, R and Brown, A and Kukushkina, V and Kalnapenkis, A and Rueger, S and Porcu, E and Kronberg, J and Kettunen, J and Lee, B and Zhang, F and Qi, T and Hernandez, JA and Arindrarto, W and Beutner, F and Dmitrieva, J and Elansary, M and Fairfax, BP and Georges, M and Hewitt, AW and Heijmans, BT and Kahonen, M and Kim, Y and Knight, JC and Kovacs, P and Krohn, K and Li, S and Loeffler, M and Marigorta, UM and Mei, H and Momozawa, Y and Muller-Nurasyid, M and Nauck, M and Nivard, MG and Penninx, BWJH and Pritchard, JK and Raitakari, OT and Rotzschke, O and Slagboom, EP and Stehouwer, CDA and Stumvoll, M and Sullivan, P and 't Hoen, PAC and Thiery, J and Tonjes, A and van Dongen, J and van Iterson, M and Veldink, JH and Volker, U and Warmerdam, R and Wijmenga, C and Swertz, M and Andiappan, A and Montgomery, GW and Ripatti, S and Perola, M and Kutalik, Z and Dermitzakis, E and Bergmann, S and Frayling, T and van Meurs, J and Prokisch, H and Ahsan, H and Pierce, BL and Lehtimaki, T and Boomsma, DI and Psaty, BM and Gharib, SA and Awadalla, P and Milani, L and Ouwehand, WH and Downes, K, BIOS Consortium, i2QTL Consortium, Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression, Nature genetics, 53, (9) pp. 1300-1310. ISSN 1061-4036 (2021) [Refereed Article]

DOI: doi:10.1038/s41588-021-00913-z


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.

Item Details

Item Type:Refereed Article
Keywords:genome wide associations, serine biosynthesis, human transcriptome, architecture, disease, relevance, disorder, links, risk
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Gene expression (incl. microarray and other genome-wide approaches)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:152896
Year Published:2021
Web of Science® Times Cited:131
Deposited By:Medicine
Deposited On:2022-08-26
Last Modified:2022-09-07

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