Big Data Center, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Department of Biomedical Informatics, College of Medicine, China Medical University, Taichung, Taiwan.
Nat Commun. 2024 Oct 29;15(1):9317. doi: 10.1038/s41467-024-53516-7.
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 in the early prevention of kidney disease.
目前针对肾功能的全基因组关联研究（GWAS）缺乏祖先多样性，限制了其在更广泛人群中的适用性。东亚人群的代表性尤其不足，尽管其终末期肾病的全球负担最高。我们对来自台湾和日本的多个 GWAS（n=244952）进行了荟萃分析，并对复制数据集（n=27058）进行了分析。这项研究在 97 个基因组风险位点中确定了 111 个主要 SNP。功能富集分析表明，与 F12 基因相关的变异和 ABCG2 中的错义突变可能通过影响炎症、凝血和尿酸代谢途径导致慢性肾脏病（CKD）。在来自台湾的独立队列（n=25345）和英国的独立队列（n=260245）中，CKD 的多基因风险评分（PRS）显著划分了 CKD 的风险（p<0.0001）。需要进一步研究以评估 PRS 在早期预防肾脏病方面的临床效果。
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