Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.
Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.
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DOI：
10.1371/journal.pone.0003490
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Martin R
中科院分区：
文献类型：
--
作者：
Comabella M;Craig DW;Camiña-Tato M;Morcillo C;Lopez C;Navarro A;Rio J;BiomarkerMS Study Group;Montalban X;Martin R
多发性硬化症是一种中枢神经系统慢性炎症性脱髓鞘疾病，具有重要的遗传成分，与HLA基因的相关性最强。为了找到与该疾病相关的新位点，我们对500,000个snp进行了基于池的全基因组关联研究。在应用了几个标准后，从微阵列中选择了320个snp，并在一个独立的西班牙高加索复制队列中进行了单独的基因分型。在该队列中验证的8个最显著的snp也在第二个美国高加索复制队列中进行基因分型以确认。最显著的关联是SNP rs3129934，它与HLA-DRB/DQA位点相邻，验证了我们基于池的策略。第二大关联信号为SNP rs1327328，它位于13号染色体的一个未注释区域，但与附近的功能元件处于连锁不平衡状态，可能在疾病易感性中起重要作用。13号染色体的这个区域以前没有在MS连锁基因组筛选中发现，它代表了该疾病的一个新的风险位点。
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.
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