A two-step procedure for constructing confidence intervals of trait loci with application to a rheumatoid arthritis dataset.
A two-step procedure for constructing confidence intervals of trait loci with application to a rheumatoid arthritis dataset.
复制标题
用于构建性状基因座置信区间并应用于类风湿性关节炎数据集的两步程序。
DOI：
10.1002/gepi.20123
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Lin,Shili
中科院分区：
文献类型：
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作者：
Papachristou,Charalampos;Lin,Shili
初步基因组筛选通常通过关注连锁信号区域的精细作图分析来成功。减少进行后续研究的区域的大小是有利的，因为这将有助于更好地解决与其相关的多重性调整问题。我们描述了一种两步方法，该方法使用置信集推理程序作为中间映射（在初步基因组筛选和精细映射之间）的工具，以进一步定位疾病位点。除了通常的 Hardy-Weiberg 和连锁平衡假设之外，所提出方法的唯一其他假设是每个感兴趣区域最多包含一个致病基因座。通过对几个双基因座疾病模型的模拟研究，我们证明我们的方法可以高精度地分离性状基因座的位置。将这种两步程序应用于关节炎研究运动国家存储库的数据也产生了非常令人鼓舞的结果。该方法不仅成功地在 6 号染色体上定位了一个特征明确的性状贡献位点，而且与基于相同数据的 LOD 支持区间对应物相比，还将其位置定位到更窄的区域。Genet。流行病。 30:18–29, 2006 年。© 2005 Wiley-Liss, Inc.
Preliminary genome screens are usually succeeded by fine mapping analyses focusing on the regions that signal linkage. It is advantageous to reduce the size of the regions where follow‐up studies are performed, since this will help better tackle, among other things, the multiplicity adjustment issue associated with them. We describe a two‐step approach that uses a confidence set inference procedure as a tool for intermediate mapping (between preliminary genome screening and fine mapping) to further localize disease loci. Apart from the usual Hardy‐Weiberg and linkage equilibrium assumptions, the only other assumption of the proposed approach is that each region of interest houses at most one of the disease‐contributing loci. Through a simulation study with several two‐locus disease models, we demonstrate that our method can isolate the position of trait loci with high accuracy. Application of this two‐step procedure to the data from the Arthritis Research Campaign National Repository also led to highly encouraging results. The method not only successfully localized a well‐characterized trait contributing locus on chromosome 6, but also placed its position to narrower regions when compared to their LOD support interval counterparts based on the same data.Genet. Epidemiol. 30:18–29, 2006. © 2005 Wiley‐Liss, Inc.