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Genetics of IgA nephrology: risks, mechanisms, and therapeutic targets

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Abstract

IgA nephropathy (IgAN) is a genetically complex multifactorial trait. Over the past decade, population-based genome-wide association studies (GWAS) have identified more than 30 IgAN risk loci, providing novel perspectives on both the epidemiology of the disease and its underlying molecular mechanisms. In addition, the association between IgAN and galactose-deficient IgA1 (Gd-IgA1) presented another avenue for genetic exploration due to the heritability of the elevated serum Gd-IgA1 levels. These endeavors also yielded and enabled refinement of polygenic risk scores, which may help identify specific groups of individuals at significantly increased risks, leading to stratifications of medical treatments. In this review, we aim to explore the existing evidence for genetic causation in IgAN. We summarize the state of genetic research in IgAN and how it has led to the reformulation of the new pathogenesis model and novel therapeutic targets.

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  • 25 April 2024

    The original online version of this article has been revised: the link to the Graphical Abstract was missing and has been added.

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Funding

Support was provided by National Science Foundation of China (82370709); Beijing Nova Program Interdisciplinary Cooperation Project (20230484426); Academy of Medical Sciences–Newton Advanced Fellowship (NAFR13\1033); Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-5–046, 2020-JKCS-009); National High Level Hospital Clinical Research Funding (Interdisciplinary Clinical Research Project of Peking University First Hospital, 2022CR41); China International Medical Foundation (Z-2017–26-2202–2); and the Joint Institute (JI) Collaboration Scholars Program at the University of Michigan Medical School. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, No. 8, Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China

    Shu Qu, Xu-jie Zhou & Hong Zhang

  2. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, People’s Republic of China

    Shu Qu, Xu-jie Zhou & Hong Zhang

  3. Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education, Peking University, Beijing, People’s Republic of China

    Shu Qu, Xu-jie Zhou & Hong Zhang

  4. Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China

    Shu Qu, Xu-jie Zhou & Hong Zhang

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Qu, S., Zhou, Xj. & Zhang, H. Genetics of IgA nephrology: risks, mechanisms, and therapeutic targets. Pediatr Nephrol (2024). https://doi.org/10.1007/s00467-024-06369-7

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