Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan

Current genome-wide association studies (GWAS) for kidney function lack ancestral diversity, limiting the applicability to broader populations. The East-Asian population is especially under-represented, despite having the highest global burden of end-stage kidney disease. We conducted a meta-analysi...

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Published in:Nature communications Vol. 15; no. 1; pp. 9317 - 16
Main Authors: Chen, Hung-Lin, Chiang, Hsiu-Yin, Chang, David Ray, Cheng, Chi-Fung, Wang, Charles C. N., Lu, Tzu-Pin, Lee, Chien-Yueh, Chattopadhyay, Amrita, Lin, Yu-Ting, Lin, Che-Chen, Yu, Pei-Tzu, Huang, Chien-Fong, Lin, Chieh-Hua, Yeh, Hung-Chieh, Ting, I-Wen, Tsai, Huai-Kuang, Chuang, Eric Y., Tin, Adrienne, Tsai, Fuu-Jen, Kuo, Chin-Chi
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 29.10.2024
Nature Publishing Group
Nature Portfolio
Subjects:
45/43
631/208/205/2138
692/4022/1585/104/1586
Adult
Aged
ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics
Coagulation
East Asian People - genetics
End-stage renal disease
Female
Genetic diversity
Genetic Predisposition to Disease
Genome-wide association studies
Genome-Wide Association Study
Glomerular Filtration Rate
Humanities and Social Sciences
Humans
Japan - epidemiology
Kidney - physiopathology
Kidney diseases
Kidneys
Male
Middle Aged
Missense mutation
multidisciplinary
Multifactorial Inheritance
Mutation, Missense
Neoplasm Proteins - genetics
Polymorphism, Single Nucleotide
Population genetics
Population studies
Populations
Renal Insufficiency, Chronic - epidemiology
Renal Insufficiency, Chronic - genetics
Risk
Risk Factors
Science
Science (multidisciplinary)
Single-nucleotide polymorphism
Taiwan - epidemiology
Uric acid
Japan
Taiwan
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Current genome-wide association studies (GWAS) for kidney function lack ancestral diversity, limiting the applicability to broader populations. The East-Asian population is especially under-represented, despite having the highest global burden of end-stage kidney disease. We conducted a meta-analysis of multiple GWASs ( n  = 244,952) on estimated glomerular filtration rate and a replication dataset ( n  = 27,058) from Taiwan and Japan. This study identified 111 lead SNPs in 97 genomic risk loci. Functional enrichment analyses revealed that variants associated with F12 gene and a missense mutation in ABCG2 may contribute to chronic kidney disease (CKD) through influencing inflammation, coagulation, and urate metabolism pathways. In independent cohorts from Taiwan ( n  = 25,345) and the United Kingdom ( n  = 260,245), polygenic risk scores (PRSs) for CKD significantly stratified the risk of CKD ( p  < 0.0001). Further research is required to evaluate the clinical effectiveness of PRS CKD in the early prevention of kidney disease. Here the authors present a large genetic study in East Asians that identifies 97 genetic regions linked to kidney function. These findings aim at better understanding chronic kidney disease in diverse populations.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-53516-7