Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
复制标题
汉族人的全基因组关联分析确定了肌萎缩侧索硬化症的两个新的易感位点。
DOI：
10.1038/ng.2627
复制
发表时间：
2013-06-01
期刊：
影响因子：
30.8
通讯作者：
Zhang, Xuejun
中科院分区：
文献类型：
--
作者：
Deng, Min;Wei, Ling;Zhang, Xuejun
为了确定肌萎缩侧索硬化症（ALS）的易感基因，我们对506名散发性ALS患者和1,859名汉族对照进行了全基因组关联研究（GWAS）。在一个由706名ALS患者和1,777名汉族对照组成的独立队列中，分析了当前GWAS提出的90个顶级SNPs和先前GWAS确定的6个SNPs。我们在1 q32（CAMK 1G，rs6703183，Pcombined= 2.92 × 10−8，OR = 1.31）和22 p11（CABIN 1和SUSD 2，rs 8141797，Pcombined= 2.35 × 10−9，OR = 1.52）发现了两个新的ALS易感基因座。这两个基因座解释了中国汉族人群疾病风险总方差的12.48%。我们没有发现与中国汉族人群中先前报道的基因座相关的证据，表明不同祖先群体之间ALS疾病易感性的遗传异质性。我们的研究确定了两个新的易感基因座，并提出了新的ALS致病机制。
To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183,Pcombined= 2.92 × 10−8, odds ratio (OR) = 1.31) and 22p11 (CABIN1andSUSD2, rs8141797,Pcombined= 2.35 × 10−9, OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.