التفاصيل البيبلوغرافية
| العنوان: |
Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets. |
| المؤلفون: |
Xu, Xiaoguang, Khunsriraksakul, Chachrit, Eales, James M., Rubin, Sebastien, Scannali, David, Saluja, Sushant, Talavera, David, Markus, Havell, Wang, Lida, Drzal, Maciej, Maan, Akhlaq, Lay, Abigail C., Prestes, Priscilla R., Regan, Jeniece, Diwadkar, Avantika R., Denniff, Matthew, Rempega, Grzegorz, Ryszawy, Jakub, Król, Robert, Dormer, John P. |
| المصدر: |
Nature Communications; 3/19/2024, Vol. 15 Issue 1, p1-29, 29p |
| مصطلحات موضوعية: |
MULTIOMICS, BLOOD pressure, REGULATION of blood pressure, KIDNEYS, GENETIC regulation, GENE expression |
| مستخلص: |
Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension. Genetic mechanisms of blood pressure regulation remain poorly defined. Here, the authors perform a kidney multi-omics study to identify 399 kidney effector genes, 11 miRNAs and 97 proteins for blood pressure and hypertension. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder