Supplementary Material for: Genome-Wide Association Studies for Albuminuria of non-Diabetic Taiwanese Population

Background Chronic renal disease (CKD), defined by reduced estimated glomerular filtration rate (eGFR) and albuminuria, imposes huge health burden worldwide. Ethnicity-specific associations were frequently observed in genome-wide association studies (GWAS). In this research, we conducted GWAS of albuminuria in the non-diabetic population of Taiwan. Subjects and Methods Non-diabetic individuals aged 30 to 70 years and without cancer history were enrolled from the Taiwan Biobank. A total of 6,768 subjects received spot urine examination. After quality control with PLINK and imputation with SHAPEIT and IMPUTE2, a total of 3,638,350 single nucleotide polymorphisms (SNPs) remained for testing. SNPs with minor allele frequency low than 0.1% were excluded. We applied linear regression for analyzing associations between SNPs and log UACR. Results We identified six loci 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) as candidate. Genetic variants in the FCRL3 gene that encodes a secretory IgA receptor were found to be associated with IgA nephropathy, which might manifest proteinuria. The PIEZO2 gene encodes a sensor for mechanical forces in mesangial cells and renin-producing cells. Conclusion We identified five new loci and one known suggestive loci for albuminuria in the non-diabetic Taiwanese population.

背景 慢性肾脏病（Chronic renal disease, CKD）以估算肾小球滤过率（estimated glomerular filtration rate, eGFR）降低和白蛋白尿（albuminuria）为定义标准，在全球范围内造成了沉重的健康负担。全基因组关联研究（genome-wide association studies, GWAS）中常观察到种族特异性的关联信号。本研究针对中国台湾地区非糖尿病人群的白蛋白尿开展了全基因组关联分析。
受试者与方法 本研究从台湾生物样本库（Taiwan Biobank）中招募了年龄30至70岁、无癌症病史的非糖尿病个体，共计6768名受试者接受随机尿检查。经PLINK进行质量控制、SHAPEIT与IMPUTE2完成基因型填充后，最终保留3638350个单核苷酸多态性（single nucleotide polymorphisms, SNPs）用于后续检测。本研究排除了次要等位基因频率低于0.1%的SNP，并采用线性回归模型分析SNP与对数转化尿白蛋白肌酐比值（log UACR）之间的关联。
结果 本研究鉴定出6个候选基因座，分别位于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）及PIEZO2（P=2.19×10⁻⁷）基因内部或邻近区域。编码分泌型IgA受体的FCRL3基因的遗传变异与IgA肾病相关，该疾病可表现为蛋白尿。PIEZO2基因编码系膜细胞与肾素生成细胞的机械力感受器。
结论 本研究在中国台湾地区非糖尿病人群中鉴定出5个全新的白蛋白尿相关基因座，以及1个已报道的提示性关联基因座。