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From mapping kidney function to mechanism and prediction

We saw impressive progress in our understanding of the genetics of kidney function and disease in 2021. Genome-wide association studies defined key common variants for kidney function and disease, and multi-omics methods, including quantitative trait analyses and single cell studies, illuminated key genes and cell types responsible for disease development.

Key advances

  • A genome-wide association study of >1 million individuals identified >400 loci in which common genetic variants are associated with kidney function1.

  • A polygenic risk score developed for estimated glomerular filtration rate demonstrated the utility of this approach for capturing risk of incident kidney diseases9.

  • Characterization of genotype-driven gene expression changes in human kidney samples identified key causal genes affecting kidney function and blood pressure4,5,7,8.

  • Single-cell RNA sequencing and single-nucleus open chromatin analysis (snATAC-seq) of human kidney samples indicate a key role of proximal tubules in kidney function and endothelial cells and distal tubule segments in blood pressure regulation4.

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Fig. 1: Results of genome-wide association studies can define key disease-driving mechanisms and predict the risk of disease development.


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The authors’ work described in this article was supported by the National Institutes of Health (NIH grant nos. R01 DK105821, R01 DK087635 and R01 DK076077 to K.S.) and by the Foundation of the NIH Type 2 Diabetes Accelerated Medicine Partnership Project through a grant to K.S. This work was also supported by a research grant from the Manpei Suzuki Diabetes Foundation to D.H.

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Correspondence to Katalin Susztak.

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Hirohama, D., Susztak, K. From mapping kidney function to mechanism and prediction. Nat Rev Nephrol (2021).

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