Discovery and prioritization of genetic determinants of kidney function in 297,355 individuals from Taiwan and Japan
Journal
Nature Communications
Journal Volume
15
Journal Issue
1
Start Page
9317
ISSN
2041-1723
Date Issued
2024-10-29
Author(s)
Hung-Lin Chen
Hsiu-Yin Chiang
David Ray Chang
Chi-Fung Cheng
Charles C. N. Wang
Chien-Yueh Lee
Yu-Ting Lin
Che-Chen Lin
Pei-Tzu Yu
Chien-Fong Huang
Chieh-Hua Lin
Hung-Chieh Yeh
I-Wen Ting
Huai-Kuang Tsai
Adrienne Tin
Fuu-Jen Tsai
Chin-Chi Kuo
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 PRSCKD in the early prevention of kidney disease.
Publisher
Springer Science and Business Media LLC
Type
journal article