Genetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Faculty of Medicine, University of Queensland, Brisbane, Australia.
J Nephrol. 2024 Jan;37(1):7-21. doi: 10.1007/s40620-023-01804-8. Epub 2023 Nov 21.
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.
肾功能受遗传因素的强烈影响，单基因和多基因因素都对肾功能有贡献。主要呈常染色体显性遗传模式的单基因疾病占成人肾脏疾病的 10%和儿童肾脏疾病的 50%。然而，肾功能也是一种复杂的特征，具有多基因结构，其中遗传因素与环境和生活方式因素相互作用。家族研究表明，肾功能具有 35-69%的显著遗传力，捕捉到了基因组的复杂性以及共享的环境因素。全基因组关联研究估计，肾功能的基于单核苷酸多态性的遗传力在 7.1%至 20.3%之间。这些遗传力估计值衡量了遗传变异对 CKD 风险的贡献程度，表明遗传因素有很强的贡献。最近针对慢性肾脏病和肾功能开发了多基因风险评分，并在大人群中进行了验证。多基因风险评分与肾功能相关，但缺乏预测个体肾功能变化的特异性。某些肾脏疾病，如膜性肾病和 IgA 肾病，具有显著的遗传成分，可能会从多基因风险评分中受益最多，以改善风险分层。肾功能的遗传研究也为开发更有针对性的治疗和干预措施提供了潜在途径。了解基因组评分的发展和验证对于指导其实施并确定在临床实践中最适当的潜在影响是必要的。在这篇综述中，我们提供了人群研究中肾功能特征遗传力的概述，探讨了肾脏疾病中的单基因和多基因概念，重点介绍了最近开发的肾功能和慢性肾脏病的多基因风险评分，并回顾了最适合纳入基因组评分的特定疾病。
