Monogenic and polygenic concepts in chronic kidney disease (CKD)
Jefferis, Julia, Hudson, Rebecca, Lacaze, Paul, Bakshi, Andrew, Hawley, Carmel, Patel, Chirag, and Mallett, Andrew (2023) Monogenic and polygenic concepts in chronic kidney disease (CKD). Journal of Nephrology. (In Press)
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Abstract
Kidney function is strongly influenced by genetic factors with both monogenic and polygenic factors contributing to kidney function. Monogenic disorders with primarily autosomal dominant inheritance patterns account for 10% of adult and 50% of paediatric kidney diseases. However, kidney function is also a complex trait with polygenic architecture, where genetic factors interact with environment and lifestyle factors. Family studies suggest that kidney function has significant heritability at 35–69%, capturing complexities of the genome with shared environmental factors. Genome-wide association studies estimate the single nucleotide polymorphism-based heritability of kidney function between 7.1 and 20.3%. These heritability estimates, measuring the extent to which genetic variation contributes to CKD risk, indicate a strong genetic contribution. Polygenic Risk Scores have recently been developed for chronic kidney disease and kidney function, and validated in large populations. Polygenic Risk Scores show correlation with kidney function but lack the specificity to predict individual-level changes in kidney function. Certain kidney diseases, such as membranous nephropathy and IgA nephropathy that have significant genetic components, may benefit most from polygenic risk scores for improved risk stratification. Genetic studies of kidney function also provide a potential avenue for the development of more targeted therapies and interventions. Understanding the development and validation of genomic scores is required to guide their implementation and identify the most appropriate potential implications in clinical practice. In this review, we provide an overview of the heritability of kidney function traits in population studies, explore both monogenic and polygenic concepts in kidney disease, with a focus on recently developed polygenic risk scores in kidney function and chronic kidney disease, and review specific diseases which are most amenable to incorporation of genomic scores. Graphical abstract: [Figure not available: see fulltext.].
| Item ID: | 81247 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 1724-6059 |
| Keywords: | Heritability, Hypertension, IgA nephropathy, Kidney function, Membranous nephropathy, Polygenic risk score |
| Copyright Information: | © Crown 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Date Deposited: | 06 Mar 2024 23:44 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320214 Nephrology and urology @ 100% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100% |
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