TY - JOUR
T1 - Kidney omics in hypertension
T2 - from statistical associations to biological mechanisms and clinical applications
AU - Tomaszewski, Maciej
AU - Morris, Andrew P.
AU - Howson, Joanna M.M.
AU - Franceschini, Nora
AU - Eales, James M.
AU - Xu, Xiaoguang
AU - Dikalov, Sergey
AU - Guzik, Tomasz J.
AU - Humphreys, Benjamin D.
AU - Harrap, Stephen
AU - Charchar, Fadi J.
N1 - Publisher Copyright:
© 2022 International Society of Nephrology
PY - 2022/9
Y1 - 2022/9
N2 - Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage.
AB - Hypertension is a major cardiovascular disease risk factor and contributor to premature death globally. Family-based investigations confirmed a significant heritable component of blood pressure (BP), whereas genome-wide association studies revealed >1000 common and rare genetic variants associated with BP and/or hypertension. The kidney is not only an organ of key relevance to BP regulation and the development of hypertension, but it also acts as the tissue mediator of genetic predisposition to hypertension. The identity of kidney genes, pathways, and related mechanisms underlying the genetic associations with BP has started to emerge through integration of genomics with kidney transcriptomics, epigenomics, and other omics as well as through applications of causal inference, such as Mendelian randomization. Single-cell methods further enabled mapping of BP-associated kidney genes to cell types, and in conjunction with other omics, started to illuminate the biological mechanisms underpinning associations of BP-associated genetic variants and kidney genes. Polygenic risk scores derived from genome-wide association studies and refined on kidney omics hold the promise of enhanced diagnostic prediction, whereas kidney omics-informed drug discovery is likely to contribute new therapeutic opportunities for hypertension and hypertension-mediated kidney damage.
KW - blood pressure
KW - gene expression
KW - genetics
KW - kidney
UR - http://www.scopus.com/inward/record.url?scp=85134730952&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2022.04.045
DO - 10.1016/j.kint.2022.04.045
M3 - Review article
C2 - 35690124
AN - SCOPUS:85134730952
SN - 0085-2538
VL - 102
SP - 492
EP - 505
JO - Kidney International
JF - Kidney International
IS - 3
ER -