Thomson Russell J, McMorran Brendan, Hoy Wendy, Jose Matthew, Whittock Lucy, Thornton Tim, Burgio Gaétan, Mathews John Duncan, Foote Simon
Centre for Research in Mathematics, School of Computing, Engineering and Mathematics, Western Sydney University, Sydney, NSW, Australia.
John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Front Genet. 2019 Apr 16;10:330. doi: 10.3389/fgene.2019.00330. eCollection 2019.
The common occurrence of renal disease in Australian Aboriginal populations such as Tiwi Islanders may be determined by environmental and genetic factors. To explore genetic contributions, we performed a genome-wide association study (GWAS) of urinary albumin creatinine ratio (ACR) in a sample of 249 Tiwi individuals with genotype data from a 370K single nucleotide polymorphism (SNP) array. A principal component analysis (PCA) of the 249 individual Tiwi cohort and samples from 11 populations included in phase III of the HapMap Project indicated that Tiwi Islanders are a relatively distinct and unique population with no close genetic relationships to the other ethnic groups. After adjusting for age and sex, the proportion of ACR variance explained by the 370K SNPs was estimated to be 37% (using the software GCTA.31; likelihood ratio = 8.06, -value = 0.002). The GWAS identified eight SNPs that were nominally significantly associated with ACR ( < 0.0005). A replication study of these SNPs was performed in an independent cohort of 497 individuals on the eight SNPs. Four of these SNPs were significantly associated with ACR in the replication sample ( < 0.05), rs4016189 located near the gene ( = 0.000751), rs443816 located in the gene encoding ( = 0.022), rs6461901 located near the gene, and rs1535656 located in the gene. The SNP rs4016189 was still significant after adjusting for multiple testing. A structural equation model (SEM) demonstrated that the rs4016189 SNP was not associated with other phenotypes such as estimated glomerular filtration rate (eGFR), diabetes, and blood pressure.
肾病在澳大利亚原住民群体（如提维岛民）中普遍存在，这可能由环境和遗传因素决定。为探究遗传因素的作用，我们对249名提维个体进行了全基因组关联研究（GWAS），这些个体拥有来自370K单核苷酸多态性（SNP）阵列的基因型数据，研究对象为尿白蛋白肌酐比值（ACR）。对249名提维个体队列以及国际人类基因组单体型图计划（HapMap计划）第三阶段纳入的11个群体的样本进行主成分分析（PCA），结果表明提维岛民是一个相对独特且与众不同的群体，与其他种族没有密切的遗传关系。在对年龄和性别进行调整后，370K SNPs解释的ACR方差比例估计为37%（使用软件GCTA.31；似然比 = 8.06，P值 = 0.002）。GWAS确定了8个与ACR名义上显著相关的SNP（P < 0.0005）。对这8个SNP在497名个体的独立队列中进行了重复研究。其中4个SNP在重复样本中与ACR显著相关（P < 0.05），rs4016189位于基因附近（P = 0.000751），rs443816位于编码的基因中（P = 0.022），rs6461901位于基因附近，rs1535656位于基因中。在进行多重检验校正后，SNP rs4016189仍然显著。结构方程模型（SEM）表明，rs4016189 SNP与其他表型如估计肾小球滤过率（eGFR）、糖尿病和血压无关。
