دورية أكاديمية
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
| العنوان: | Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression |
|---|---|
| المؤلفون: | 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, M. G. P., 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, C. D. A., Stumvoll, M., Sullivan, P., t Hoen, P. A. C., 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. |
| بيانات النشر: | Nature |
| سنة النشر: | 2021 |
| المجموعة: | RD&E Research Repository (Royal Devon and Exeter NHS Foundation Trust) |
| الوصف: | 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. ; This article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site. ; Accepted version (6 months embargo), submitted version |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1038/s41588-021-00913-zTest; Nat Genet. 2021 Sep;53(9):1300-1310. doi:10.1038/s41588-021-00913-z. Epub 2021 Sep 2.; https://rde.dspace-express.com/handle/11287/622171Test; Nature genetics; PMC8432599 |
| DOI: | 10.1038/s41588-021-00913-z |
| الإتاحة: | https://doi.org/10.1038/s41588-021-00913-zTest https://rde.dspace-express.com/handle/11287/622171Test |
| حقوق: | © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. |
| رقم الانضمام: | edsbas.90FC18AD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41588-021-00913-z |
|---|