Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Public Health and Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Sci Rep. 2019 Mar 21;9(1):4981. doi: 10.1038/s41598-019-41434-4.
There is a paucity of genome-wide association study on Han Chinese gout patients. We performed a genome-wide association meta-analysis on two Taiwanese cohorts consisting of 758 gout cases and 14166 controls of Han Chinese ancestry. All the participants were recruited from the Taiwan Biobank. For pathway analysis, we applied ICSNPathway (Identify candidate Causal SNPs and Pathways) analysis, and to investigate whether expression-associated genetic variants contribute to gout susceptibility, we systematically integrated lymphoblastoid expression quantitative trait loci (eQTL) and genome-wide association data of gout using Sherlock, a Bayesian statistical frame-work. In the meta-analysis, we found 4 SNPs that reached genome-wide statistical significance (P < 5.0 × 10). These SNPs are in or close to ABCG2, PKD2 and NUDT9 gene on chromosome 4. ICSNPathway analysis identified rs2231142 as the candidate causal SNP, and ABCG2 as the candidate gene. Sherlcok analysis identified three genes, which were significantly associated with the risk of gout (PKD2, NUTD9, and NAP1L5). To conclude, we reported novel susceptible loci for gout that has not been previously addressed in the literature.
关于汉族痛风患者的全基因组关联研究很少。我们对来自台湾生物银行的两个台湾汉族队列（共 758 例痛风病例和 14166 例对照）进行了全基因组关联荟萃分析。对于通路分析，我们应用了 ICSNPathway（识别候选因果 SNP 和通路）分析，为了研究表达相关的遗传变异是否导致痛风易感性，我们使用 Sherlock（一种贝叶斯统计框架）系统地整合了浆细胞瘤表达数量性状基因座（eQTL）和痛风的全基因组关联数据。在荟萃分析中，我们发现了 4 个达到全基因组统计学意义的 SNP（P<5.0×10）。这些 SNP 位于或接近染色体 4 上的 ABCG2、PKD2 和 NUDT9 基因。ICSNPathway 分析确定 rs2231142 为候选因果 SNP，ABCG2 为候选基因。Sherlock 分析确定了三个与痛风风险显著相关的基因（PKD2、NUTD9 和 NAP1L5）。总之，我们报告了痛风的新易感基因座，这在文献中尚未得到解决。
