Genome-Wide Association Studies for Albuminuria of Nondiabetic Taiwanese Population

Abstract

Introduction: Chronic kidney disease, which is defined by a reduced estimated glomerular filtration rate and albuminuria, imposes a large health burden worldwide. Ethnicity-specific associations are frequently observed in genome-wide association studies (GWAS). This study conducts a GWAS of albuminuria in the nondiabetic population of Taiwan. Methods: Nondiabetic individuals aged 30–70 years without a history of cancer were enrolled from the Taiwan Biobank. A total of 6,768 subjects were subjected to a spot urine examination. After quality control using PLINK and imputation using SHAPEIT and IMPUTE2, a total of 3,638,350 single-nucleotide polymorphisms (SNPs) remained for testing. SNPs with a minor allele frequency of less than 0.1% were excluded. Linear regression was used to determine the relationship between SNPs and log urine albumin-to-creatinine ratio. Results: Six suggestive loci are identified in or near the FCRL3 (p = 2.56 × 10⁻⁶), TMEM161 (p = 4.43 × 10⁻⁶), EFCAB1 (p = 2.03 × 10⁻⁶), ELMOD1 (p = 2.97 × 10⁻⁶), RYR3 (p = 1.34 × 10⁻⁶), and PIEZO2 (p = 2.19 × 10⁻⁷). Genetic variants in the FCRL3 gene that encode a secretory IgA receptor are found to be associated with IgA nephropathy, which can manifest as proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Five SNPs with a p-value between 5 × 10⁻⁶ and 5 × 10⁻⁵ are also identified in five genes that may have a biological role in the development of albuminuria. Conclusion: Five new loci and one known suggestive locus for albuminuria are identified in the nondiabetic Taiwanese population.