التفاصيل البيبلوغرافية
| العنوان: |
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits |
| المؤلفون: |
Xu, X, Eales, JM, Akbarov, A, Guo, H, Becker, L, Talavera, D, Ashraf, F, Nawaz, J, Pramanik, S, Bowes, J, Jiang, X, Dormer, J, Denniff, M, Antczak, A, Szulinska, M, Wise, I, Prestes, PR, Glyda, M, Bogdanski, P, Zukowska-Szczechowska, E, Berzuini, C, Woolf, AS, Samani, NJ, Charchar, FJ, Tomaszewski, M |
| بيانات النشر: |
NATURE PUBLISHING GROUP |
| سنة النشر: |
2018 |
| المجموعة: |
The University of Melbourne: Digital Repository |
| الوصف: |
Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
2041-1723 |
| Relation: |
pii: 10.1038/s41467-018-07260-4; Xu, X., Eales, J. M., Akbarov, A., Guo, H., Becker, L., Talavera, D., Ashraf, F., Nawaz, J., Pramanik, S., Bowes, J., Jiang, X., Dormer, J., Denniff, M., Antczak, A., Szulinska, M., Wise, I., Prestes, P. R., Glyda, M., Bogdanski, P. ,. Tomaszewski, M. (2018). Molecular insights into genome-wide association studies of chronic kidney disease-defining traits. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-07260-4.; http://hdl.handle.net/11343/251079 |
| الاتاحة: |
http://hdl.handle.net/11343/251079 |
| Rights: |
CC BY ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: |
edsbas.28A1C13F |
| قاعدة البيانات: |
BASE |
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