Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata
Genome-wide pooling approach identifies SPATA5 as a new susceptibility locus for alopecia areata
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DOI：
10.1038/ejhg.2011.185
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发表时间：
2012-03-01
影响因子：
5.2
通讯作者：
Betz, Regina C.
中科院分区：
文献类型：
--
作者：
Forstbauer, Lina M.;Brockschmidt, Felix F.;Betz, Regina C.
斑秃是一种常见的脱发疾病，被认为是一种组织特异性自身免疫性疾病。以前的研究已经确定了一些再生障碍性贫血易感基因，其中大多数与自身免疫有关。为了识别新的遗传变异并进一步阐明再生障碍性贫血的遗传基础，我们使用混合DNA基因分型策略进行了全基因组关联研究(729例，656例对照)。关联最强的是人类白细胞抗原区域的变异体，这证实了汇集策略的有效性。在一个独立的复制样本(454例，1364例对照)中分析了选定的前61个单核苷酸多态(SNPs)。只有一个HLA区外的SNP(Rs304650)显示有显著关联。然后在第二个独立的复制样本(537个病例，657个对照)中对该SNP进行分析。这一发现没有在显著水平上重复，但显示出相同的趋势。然后对两个复制样本进行联合分析，发现SNP rs304650与P=3.43 x 10(-4)显著相关(OR=1.24(1.10-1.39))。该SNP定位于4号染色体SPATA5(精子发生相关蛋白5)基因的内含子区域，提示SPATA5是AA的新易感基因。《欧洲人类遗传学杂志》(2012年)20326332；doi：10.1038/ejhg.2011.185；2011年10月26日在线发布
Alopecia areata (AA) is a common hair loss disorder, which is thought to be a tissue-specific autoimmune disease. Previous research has identified a few AA susceptibility genes, most of which are implicated in autoimmunity. To identify new genetic variants and further elucidate the genetic basis of AA, we performed a genome-wide association study using the strategy of pooled DNA genotyping (729 cases, 656 controls). The strongest association was for variants in the HLA region, which confirms the validity of the pooling strategy. The selected top 61 single-nucleotide polymorphisms (SNPs) were analyzed in an independent replication sample (454 cases, 1364 controls). Only one SNP outside of the HLA region (rs304650) showed significant association. This SNP was then analyzed in a second independent replication sample (537 cases, 657 controls). The finding was not replicated on a significant level, but showed the same tendency. A combined analysis of the two replication samples was then performed, and the SNP rs304650 showed significant association with P=3.43 x 10(-4) (OR=1.24 (1.10-1.39)). This SNP maps to an intronic region of the SPATA5 (spermatogenesis-associated protein 5) gene on chromosome 4. The results therefore suggest the SPATA5 locus is a new susceptibility locus for AA. European Journal of Human Genetics (2012) 20, 326-332; doi:10.1038/ejhg.2011.185; published online 26 October 2011