Xiaoguang Xu, Chachrit Khunsriraksakul, James M Eales, Sebastien Rubin, David Scannali, Sushant Saluja, David Talavera, Havell Markus, Lida Wang, Maciej Drzal, Akhlaq Maan, Abigail C Lay, Priscilla R Prestes, Jeniece Regan, Avantika R Diwadkar, Matthew Denniff, Grzegorz Rempega, Jakub Ryszawy, Robert Król, John P Dormer, Monika Szulinska, Marta Walczak, Andrzej Antczak, Pamela R Matías-García, Melanie Waldenberger, Adrian S Woolf, Bernard Keavney, Ewa Zukowska-Szczechowska, Wojciech Wystrychowski, Joanna Zywiec, Pawel Bogdanski, A H Jan Danser, Nilesh J Samani, Tomasz J Guzik, Andrew P Morris, Dajiang J Liu, Fadi J Charchar, Maciej Tomaszewski
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)...
March 19, 2024: Nature Communications