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Meta-Analysis

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Yukinori Okada et al. Nat Genet. .

Abstract

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

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Figures

Figure 1
Figure 1. Manhattan plots of the GWAS meta-analysis for kidney function–related traits
Shown are the −log10 (P values) of the SNPs for the concentrations of blood urea nitrogen, serum creatinine and uric acid, and for eGFRcrea. The genetic loci that satisfied the genome-wide significance threshold of P < 5.0 × 10−8 (gray horizontal dotted line) in the combined study of the GWAS meta-analysis and replication are labeled for each of the traits. The newly identified loci are colored red, and the previously known loci are colored blue. The SNPs for which the P value was smaller than 1.0 × 10−20 are indicated at the upper limit of each plot.
Figure 2
Figure 2. Venn diagram of pleiotropic associations of the identified loci
Genetic loci identified in the study are classified on the basis of the results of the pleiotropic association study of kidney function–related traits (Table 2 and Supplementary Table 8). Genes that showed significant associations with risk for stage 3+ CKD are colored red.
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