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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, Claringbould, A, Westra, HJ, Bonder, MJ, Deelen, P, Zeng, B, Kirsten, H, Saha, A, Kreuzhuber, R, Yazar, S, Brugge, H, Oelen, R, de Vries, DH, van der Wijst, MGP, Kasela, S, Pervjakova, N, Alves, I, Favve, MJ, Agbessi, M, Christiansen, MW, Jansen, R, Seppala, I, Tong, L, Teumer, A, Schramm, K, Hemani, G, Verlouw, J, Yaghootkar, H, Sonmez Flitman, R, Brown, A, Kukushkina, V, Kalnapenkis, A, Rueger, S, Porcu, E, Kronberg, J, Kettunen, J, Lee, B, Zhang, F, Qi, T, Hernandez, JA, Arindrarto, W, Beutner, F, Dmitrieva, J, Elansary, M, Fairfax, BP, Georges, M, Hewitt, AW ORCID: 0000-0002-5123-5999, Heijmans, BT, Kahonen, M, Kim, Y, Knight, JC, Kovacs, P, Krohn, K, Li, S, Loeffler, M, Marigorta, UM, Mei, H, Momozawa, Y, Muller-Nurasyid, M, Nauck, M, Nivard, MG, Penninx, BWJH, Pritchard, JK, Raitakari, OT, Rotzschke, O, Slagboom, EP, Stehouwer, CDA, Stumvoll, M, Sullivan, P, 't Hoen, PAC, Thiery, J, Tonjes, A, van Dongen, J, van Iterson, M, Veldink, JH, Volker, U, Warmerdam, R, Wijmenga, C, Swertz, M, Andiappan, A, Montgomery, GW, Ripatti, S, Perola, M, Kutalik, Z, Dermitzakis, E, Bergmann, S, Frayling, T, van Meurs, J, Prokisch, H, Ahsan, H, Pierce, BL, Lehtimaki, T, Boomsma, DI, Psaty, BM, Gharib, SA, Awadalla, P, Milani, L, Ouwehand, WH and Downes, K 2021 , 'Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression' , Nature genetics, vol. 53, no. 9 , pp. 1300-1310 , doi:

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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 Type: Article
Authors/Creators: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
Keywords: genome wide associations, serine biosynthesis, human transcriptome, architecture, disease, relevance, disorder, links, risk
Journal or Publication Title: Nature genetics
Publisher: Nature
ISSN: 1061-4036
DOI / ID Number:
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