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

Hung-Lin Chen; Hsiu-Yin Chiang; David Ray Chang; Chi-Fung Cheng; Charles C N Wang; Tzu-Pin Lu; Chien-Yueh Lee; Amrita Chattopadhyay; Yu-Ting Lin; Che-Chen Lin; Pei-Tzu Yu; Chien-Fong Huang; Chieh-Hua Lin; Hung-Chieh Yeh; I-Wen Ting; Huai-Kuang Tsai; Eric Y Chuang; Adrienne Tin; Fuu-Jen Tsai; Chin-Chi Kuo

doi:10.1038/s41467-024-53516-7

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

Nat Commun. 2024 Oct 29;15(1):9317. doi: 10.1038/s41467-024-53516-7.

Authors

Hung-Lin Chen^{1

2}, Hsiu-Yin Chiang^{1

2}, David Ray Chang^{3

4}, Chi-Fung Cheng¹, Charles C N Wang⁵, Tzu-Pin Lu⁶, Chien-Yueh Lee^{7

8}, Amrita Chattopadhyay^{1

9}, Yu-Ting Lin^{1

2}, Che-Chen Lin¹, Pei-Tzu Yu¹, Chien-Fong Huang¹, Chieh-Hua Lin¹, Hung-Chieh Yeh³, I-Wen Ting³, Huai-Kuang Tsai¹⁰, Eric Y Chuang^{11

12

13}, Adrienne Tin¹⁴, Fuu-Jen Tsai^#^{15

16

17

18}, Chin-Chi Kuo^#^{19

20

21

22

23}

Affiliations

¹ Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan.
² Department of Biomedical Informatics, College of Medicine, China Medical University, Taichung, Taiwan.
³ Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
⁵ Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
⁶ Institute of Health Data Analytics and Statistics, Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
⁷ Master Program in Artificial Intelligence, Innovation Frontier Institute of Research for Science and Technology, National Taipei University of Technology, Taipei, Taiwan.
⁸ Department of Electrical Engineering, National Taipei University of Technology, Taipei, Taiwan.
⁹ Institute of Epidemiology and Preventive Medicine, Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
¹⁰ Institute of Information Science, Academia Sinica, Taipei, Taiwan.
¹¹ Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan.
¹² Department of Electrical Engineering, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.
¹³ Graduate Institute of Biomedical Electronics and Bioinformatics, College of Electrical Engineering and Computer Science, National Taiwan University, Taipei, Taiwan.
¹⁴ Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA.
¹⁵ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. [email protected].
¹⁶ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. [email protected].
¹⁷ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan. [email protected].
¹⁸ Department of Medical Laboratory Science & Biotechnology, Asia University, Taichung, Taiwan. [email protected].
¹⁹ Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan. [email protected].
²⁰ Department of Biomedical Informatics, College of Medicine, China Medical University, Taichung, Taiwan. [email protected].
²¹ Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan. [email protected].
²² Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan. [email protected].
²³ College of Medicine, China Medical University, Taichung, Taiwan. [email protected].

^# Contributed equally.

Abstract

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.

Publication types

Meta-Analysis

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics
Adult
Aged
East Asian People / genetics
Female
Genetic Predisposition to Disease*
Genome-Wide Association Study
Glomerular Filtration Rate*
Humans
Japan / epidemiology
Kidney / physiopathology
Male
Middle Aged
Multifactorial Inheritance
Mutation, Missense
Neoplasm Proteins / genetics
Polymorphism, Single Nucleotide
Renal Insufficiency, Chronic* / epidemiology
Renal Insufficiency, Chronic* / genetics
Risk Factors
Taiwan / epidemiology

Substances

ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily G, Member 2
Neoplasm Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding