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Introduction to Genomics of Kidney Disease Implications, Discovery, and Translation

Matthew G. Sampson, Caroline S. Fox

In both clinical care and research, genetics and genomics are no longer solely in the domain of geneticists and basic science researchers. On the clinical side, there is expanding recognition of the utility of genetic testing in patients with kidney disease and an increased ability to order it. As such, the number of patients who should be considered for genetic testing in a timely manner overwhelms the bandwidth of the available clinical geneticists, genetic counselors, and payor systems.Thus, it is incumbent on nephrologists to become increasingly comfortable incorporating genetic testing into their clinical toolbox in the appropriate clinical context. This can be in the form of ordering the correct genetic testin theappropriate clinical setting, interpreting results, or appraising the literature. Beyond the clinical application of genomics, there is also an outstanding opportunity for nephrologists and/or kidney-focused investigators driven to have an effect via research. Tools and methods to generate and analyze human genomics data are enabling our community to make important discoveries. The costs of sequencing and computing have decreased, while the ease of use of some analytic strategies has increased. Together, these factors are democratizing applied kidney genomics research, allowing more individuals to drive or participate in research to answer questions that arise in the clinic.It is within this context that we have the pleasure to serve as guest editors on a series we have affectionately dubbed “Kidney Genomics 2020.” We had two major, and equally important, aims when assembling the topics and authors for this series. First and foremost, we wanted to inform readers about ways in which existing kidney genomic discoveries are already having an effect in the clinical arena and in ongoing research efforts. At the same time, we wanted the readership to understand the multiple forms of genomic variation that can contribute to kidney disease (“genetic architecture”) and methods by which we can discover and characterize it. We find this to be particularly important given the dynamism of kidney genomics, with many aspects that were not covered in our clinical training. Combining these two aims should allow readers to participate in any part of a kidney applied genomics ecosystem—whether by working to discover/refine genomic signatures of

kidney disease, by applying genomic insights for improved patient care, or both. Our series will be presented in three parts. The first set of articles will focus on genomic methods for discovery and translation in kidney disease. We will begin with a review of the genetic architecture of kidney disease to provide our readership a foundation in how to think about the genetic underpinnings of kidney disease. Layered on top of this will be methodologic approaches for genomic discovery and subsequent mechanistic characterization, including the use of genome-wide association studies, single-cell sequencing, organoids, metabolomics and proteomics, systems biology, and functional studies. The second portion of the series will center on applied genomics of kidney disease. Here, we will focus on three topics including the use of genetics and genomics in the pharmaceutical setting; the role of clinical genetic screening in kidney disease; and the ethical, legal, and social implications around the return of genomic results and potential for clinical actionability. In the third and final section of the series, we will focus onspecificareasofbiologyandassociatedkidneydiseases, with a focus on genomics and how it can provide insights into disease pathophysiology, prevention, and treatment. The series will cover topics ranging from diseases of the podocyte, the tubules, kidney development, autoimmune disease and disorders of complement, and finally around the implications of unbiased genetic screens and APOL1. This collection of articles is timely given the explosion of research into the area of genetics and genomics of kidney disease. It will enable us to achieve our twofold goal of enabling clinicians and researchers to better understand and interpret the current clinical applications of these tools, and how one may participate in research efforts to advance the care of patients with kidney diseases through genomic discovery. We invite you to join us in our journey of exploration.


Dr. Fox is a full-time employee of Merck & Co., Inc.

Dr. Sampson reports personal fees from Maze Therapeutics outside the submitted work.


This study article was supported by National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disorders grants DK108805 and DK119380.

Published online ahead of print. Publication date available at