Replication of Gout/Urate Concentrations GWAS Susceptibility Loci Associated with Gout in a Han Chinese Population.
Replication of Gout/Urate Concentrations GWAS Susceptibility Loci Associated with Gout in a Han Chinese Population.
复制标题
中国汉族人群中痛风/尿酸盐浓度的 GWAS 易感性位点的复制
DOI：
10.1038/s41598-017-04127-4
复制
发表时间：
2017-06-22
影响因子：
4.6
通讯作者：
Li C
中科院分区：
文献类型：
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作者：
Li Z;Zhou Z;Hou X;Lu D;Yuan X;Lu J;Wang C;Han L;Cui L;Liu Z;Chen J;Cheng X;Zhang K;Ji J;Jia Z;Ma L;Xin Y;Liu T;Yu Q;Ren W;Wang X;Li X;Mi QS;Shi Y;Li C
痛风是一种慢性疾病，由血清尿酸(SU)升高引起。以往的全基因组关联研究已经确定了数十个SU/痛风的易感基因，但很少有针对中国血统的研究。在这里，我们试图广泛调查这些基因座是否会导致中国汉族人患痛风的风险。在1255名痛风患者和1848名对照的汉族队列中，分析了2255个连锁不平衡(LD)变异和GWA型SU/GOT型相关变异。采用累积遗传风险评分分析来评估多个“风险”变异对痛风发病率的累积影响。在我们的样本中，23个(41%)LD剪枝变异体集合(n = 56)与痛风有名义关联(p <； 0.05)。一些已报道的痛风相关基因座(除ALDH16A1外)，包括ABCG2、SLC2A9、GCKR、ALDH2和CNIH2，被复制。累积遗传风险得分分析表明，随着痛风相关基因座上风险等位基因数量的增加(≥8)，个体患痛风的风险增加。在以前的GWAS中发现的大多数痛风相关基因座在一个独立的中国队列中得到了证实，SU相关基因座也赋予了痛风的易感性。这些发现为痛风的遗传关联提供了重要信息。
Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple “risk” variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p < 0.05). Some of the previously reported gout associated loci (exceptALDH16A1), includingABCG2,SLC2A9,GCKR,ALDH2andCNIH2, were replicated. Cumulative genetic risk score analyses showed that the risk of gout increased for individuals with the growing number (≥8) of the risk alleles on gout associated loci. Most of the gout associated loci identified in previous GWAS were confirmed in an independent Chinese cohort, and the SU associated loci also confer susceptibility to gout. These findings provide important information of the genetic association of gout.