Genomewide Association Study of Leprosy
Genomewide Association Study of Leprosy
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DOI：
10.1056/nejmoa0903753
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发表时间：
2009-12-31
影响因子：
158.5
通讯作者：
Liu, Jian-Jun
中科院分区：
文献类型：
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作者：
Zhang, Fu-Ren;Huang, Wei;Liu, Jian-Jun
背景麻风分枝杆菌寄主范围狭窄，难以在培养上生长，限制了对麻风的研究和生物学认识。宿主遗传因素被认为影响感染的易感性和疾病的进展。方法：我们使用Human 610-Quad BeadChip(Illumina)对706名患者和1225名对照进行了两阶段的全基因组关联研究。然后，在全基因组相关性研究中，我们测试了三个独立的复制集，以确定麻风病的存在与93个单核苷酸多态(SNPs)之间的关联，这些SNPs与疾病的相关性最强。这些复制集合总共包括3254名患者和5955名对照。我们还对这93个SNP与疾病之间的关联性(或缺乏关联性)进行了异质性测试，根据临床亚型(多菌型和少菌型)进行分层。
BACKGROUNDThe narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression.METHODSWe performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary).RESULTSWe observed a significant association (P