Unveiling the genetic architecture of kidney function in the Korean population

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Kidney Res Clin Pract. 2024;43(3):257-259
Publication date (electronic) : 2024 May 28
doi : https://doi.org/10.23876/j.krcp.24.098
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
Correspondence: Sehoon Park Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea. E-mail: mailofsehoon@gmail.com
Received 2024 April 10; Accepted 2024 April 28.

Chronic kidney disease (CKD) poses a significant global health burden, affecting hundreds of million people worldwide. The current nephrology society consensus has announced that CKD is under-recognized and further global awareness and resources are necessary to solve the critical socioeconomic burden of kidney disease [1]. Its multifactorial nature, with roots in both environmental exposures and genetic predispositions, complicates its management and necessitates a deeper understanding of its etiology. Historically, the genetic exploration of CKD has predominantly focused on populations of European descent, with seminal works such as those by Köttgen et al. [2] and Wuttke et al. [3] identifying multiple genetic loci associated with renal function indicators and CKD. Furthermore, the knowledge of genetic architecture of kidney function expanded from the recent multiethnic meta-analysis of genome-wide association studies (GWAS) and epi-GWAS [4,5]. Those studies, mainly led by the CKDGen Consortium [6], have been instrumental in unraveling the genetic landscape of CKD.

However, the genetic structure of CKD exhibits considerable variation across different populations, underscoring the necessity for research within diverse ethnic groups. The study by Lee et al. [7] addresses this gap by analyzing over five million SNPs from 58,406 participants, employing sophisticated meta-GWAS and fine-mapping techniques. The article leverages the extensive data from the Korean Genome and Epidemiology Study (KoGES), to illuminate the association between SNPs and estimated glomerular filtration rate (eGFR), a vital measure of kidney function. This study not only enhances our understanding of the genetic factors influencing CKD in Koreans but also serves as a critical step toward personalizing medical interventions based on genetic predispositions.

The identification of 1,360 loci associated with eGFR at a genome-wide significant level, with 399 loci validated with additional biomarkers, significantly contributes to our comprehension of the intricate genetic framework governing kidney function. This achievement is particularly notable given the unique genetic background of the Korean population, which may harbor specific genetic variants influencing CKD susceptibility and progression which may be useful in our society.

The relevance of Lee et al.’s findings [7] is further magnified when considering the implications of these genetic insights for clinical practice and public health. Understanding the genetic determinants of CKD can facilitate the development of predictive models for disease risk, enabling early intervention strategies and tailored treatment plans. The genetic variants identified from the study may be used to construct polygenic risk scores, a useful method to quantify one’s genetic predisposition towards a disease in precision medicine [8].

Moreover, the identification of novel single nucleotide polymorphisms (SNPs) and their associated pathways offers new targets for therapeutic intervention, potentially leading to innovative treatments for CKD. The study’s integration of functional mapping and annotation tools, such as MAGMA (Multi-marker Analysis of GenoMic Annotation) gene analysis and FUMA (Functional Mapping and Annotation of Genome-Wide Association Studies) , underscores the significance of genetic pathways and tissues in kidney function. The concordance with the work conducted by the GTEx Consortium [8], which detailed genetic regulatory effects across human tissues, and Pattaro et al. [9], who identified genetic associations highlighting relevant cell types and biological pathways, reinforces the knowledge that kidney function and disease are influenced by a complex interplay of genetic factors. Together with the previous literatures, the GWAS in the Korean population may facilitate future studies to validate the identified genetic loci in relation to their potential diagnostic or therapeutic values. The identified 20 putative genes may be prioritized in future mechanistic researches in the Korean population, additionally expanding our knowledge of pathways related to kidney function.

Lee et al. [7] also highlights the importance of inclusivity in genetic research. The genetic determinants of disease can vary significantly between populations, and studies focusing exclusively on certain ethnic groups may not fully capture the global genetic diversity associated with health and disease. By broadening the scope of genetic studies to include underrepresented populations, researchers can develop a more comprehensive understanding of the genetic basis of diseases like CKD. Moreover, the Korean population-specific findings may be used in future analytic researches (i.e. Mendelian randomization) in Koreans contributing to the expansion of knowledge for the causal pathways of CKD in the nation [10].

On the other hand, this study has a common limitation of the current GWAS literature analyzing kidney function traits; kidney function is determined by surrogate markers (e.g. creatinine or cystatin C-based parameters). In clinical practice, eGFR has remaining limitations as creatinine or even cystatin C levels are affected by non-kidney factors. Even considering that eGFR is the most commonly used clinical marker, there’s a lingering limitation that GWAS analyses targeting such markers may miss genetic variant information related to actual kidney function or include variants related to pleiotropic phenotypes. To overcome this, this study and others have conducted analyses on secondary markers like blood urea nitrogen . However, it’s necessary to remember that exploration into the genetic architecture of the measured but not eGFR needs additional investigation in the future.

In conclusion, the study by Lee et al. [7] is an important contribution to the genetic study of CKD in a Korean population. It exemplifies the critical need for incorporating diverse populations into genetic research to uncover the intricate tapestry of genetic factors influencing health and disease. The integration of the current findings with global genetic studies of CKD will be crucial for developing a holistic understanding of CKD’s genetic architecture and associated pathways. Such comprehensive insights hold the key to unlocking new frontiers in the prevention, diagnosis, and treatment of CKD, heralding an era of precision nephrology that benefits populations worldwide.


Conflicts of interest

The author has no conflicts of interest to declare.

Data sharing statement

The data presented in this study are available from the corresponding author upon reasonable request.


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