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首页> 外文期刊>Arthritis and Rheumatism >The chromosome 7q region association with rheumatoid arthritis in females in a british population is not replicated in a North American case-control series.
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The chromosome 7q region association with rheumatoid arthritis in females in a british population is not replicated in a North American case-control series.

机译：在北美病例对照系列中，未复制英国人群中女性与类风湿性关节炎相关的染色体7q区。

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OBJECTIVE: The single-nucleotide polymorphism (SNP) rs11761231 on chromosome 7q has been reported to be sexually dimorphic marker for rheumatoid arthritis (RA) susceptibility in a British population. We sought to replicate this finding and to better characterize susceptibility alleles in the region in a North American population. METHODS: DNA from 2 North American collections of RA patients and controls (1,605 cases and 2,640 controls) was genotyped for rs11761231 and 16 additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests were performed for each collection and also separately, contrasting male cases with male controls and female cases with female controls. Principal components analysis (EigenStrat) was used to determine association with RA before and after adjusting for population stratification in the subset of the samples for which there were whole-genome SNP data (772 cases and 1,213 controls). RESULTS: We failed to replicate an association of the 7q region with RA. Initially, rs11761231 showed evidence for association with RA in the North American Rheumatoid Arthritis Consortium (NARAC) collection (P = 0.0073), and rs11765576 showed association with RA in both the NARAC (P = 0.038) and RA replication (P = 0.0013) collections. These markers also exhibited sex differentiation. However, in the whole-genome subset, neither SNP showed significant association with RA after correction for population stratification. CONCLUSION: While 2 SNPs on chromosome 7q appeared to be associated with RA in a North American cohort, the significance of this finding did not withstand correction for population substructure. Our results emphasize the need to carefully account for population structure to avoid false-positive disease associations.
机译：目的：据报道，在英国人群中，第7q染色体上的单核苷酸多态性（SNP）rs11761231是类风湿关节炎（RA）易感性的双态性标记。我们试图复制这一发现，以更好地表征北美人口中该地区的易感等位基因。方法：使用Sequenom iPlex分析法对rs11761231和其他16个染色体7q标签SNP的2种北美RA患者和对照（1,605例和2,640例对照）的DNA进行基因分型。对每个集合进行了关联测试，也分别进行了关联测试，对比了男性病例与男性对照和女性病例与女性对照。在具有全基因组SNP数据的样本子集中（772例和1,213例对照）中，使用主成分分析（EigenStrat）来确定与人群分层调整前后的RA关系。结果：我们未能复制7q地区与RA的关联。最初，rs11761231在北美类风湿关节炎协会（NARAC）馆藏中显示与RA关联的证据（P = 0.0073），而rs11765576在NARAC（P = 0.038）和RA复制（P = 0.0013）馆藏中均与RA关联。 。这些标记物也表现出性别差异。但是，在全基因组子集中，校正群体分层后，两个SNP均未显示出与RA显着相关。结论：尽管在北美一个队列中，染色体7q上的2个SNP似乎与RA相关，但这一发现的意义并未承受对人口亚结构的校正。我们的结果强调需要仔细考虑人口结构，以避免假阳性疾病的关联。

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