Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20
Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20
复制标题
DOI：
10.1038/ng.396
复制
发表时间：
2009-07-01
期刊：
影响因子：
30.8
通讯作者：
Willoughby, Ernest
中科院分区：
文献类型：
--
作者：
Bahlo, Melanie;Booth, David R.;Willoughby, Ernest
为了识别多发性硬化症（MS）易感基因座，我们对1，618例病例进行了全基因组关联研究（GWAS），并使用了3，413名对照的共享数据。我们在一组独立的2，256例病例和2，310例对照中进行了重复研究，共3，874例病例和5，723例对照。我们在染色体12 q13 -14上鉴定了风险相关SNP（rs703842，P = 5.4 x 10（-11）; rs 10876994，P = 2.7 x 10（-10）; rs 12368653，P = 1.0 x 10（-7））和染色体20 q13上的CD 40上游（rs6074022，P = 1.3 × 10（-7）; rs1569723，P = 2.9 × 10（-7））。这两个基因座也与其他自身免疫性疾病相关（1-5）。我们还复制了几个已知的MS关联（HLA-DR 15，P = 7.0 × 10（-184）; CD58，P = 9.6 × 10（-8）; EV15-RPL 5，P = 2.5 × 10（-6）; IL 2RA，P = 7.4 × 10（-6）; CLEC16 A，P = 1.1 × 10（-4）; IL 7R，P = 1.3 × 10（-3）; TYK 2，P = 3.5 × 10（-3）），并观察到EV 15-RPL 5和HLA-DR 15中SNP之间的统计学相互作用（P = 0.001）。
To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases(1-5). We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).