A novel bayesian graphical model for genome-wide multi-SNP association mapping.
A novel bayesian graphical model for genome-wide multi-SNP association mapping.
复制标题
全基因组多SNP关联映射的新型贝叶斯图形模型。
DOI：
10.1002/gepi.20661
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发表时间：
2012-01
影响因子：
2.1
通讯作者：
Zhang, Yu
中科院分区：
文献类型：
--
作者：
Zhang, Yu
大多数疾病关联图谱算法都基于一次测试一种变异的假设检验程序。当疾病突变被多个变体联合标记或存在基因与基因相互作用时，这些方法就会失去作用。附近的变体也是相关的，忽略变体之间的依赖性的程序将不可避免地产生冗余结果。由于当前全基因组疾病关联研究中对大量变异进行了基因分型，因此强烈需要同步多变异关联作图算法。我们提出了一种新的贝叶斯方法，用于在全基因组病例对照研究中自动检测多变量联合关联。我们的方法比现有工具提高了功能和特异性。我们将联合概率模型拟合到整个数据并同时识别疾病变异。该方法动态地解释了变体之间的强连锁不平衡（LD）。因此，只会识别出主要的疾病变异，而由于 LD 效应而导致的所有次要关联都会被过滤掉。我们的方法能够以更高的分辨率更好地查明疾病变异。该方法对于全基因组研究来说计算效率也很高。当应用于包含 4,720 名个体的 401,473 个变异的炎症性肠病 (IBD) 真实数据集时，我们的方法在相同数据中检测到了所有先前报告的 IBD 位点，并恢复了两个丢失的位点。我们进一步检测到两种新颖的染色体间相互作用。第一个位于 STAT3 和 PARD6G 之间，第二个位于 DLG5 和 5p14 的基因间区域之间。我们在一项独立研究中进一步验证了这两种相互作用。
Most disease association mapping algorithms are based on hypothesis testing procedures that test one variant at a time. Those methods lose power when the disease mutations are jointly tagged by multiple variants, or when gene-gene interaction exist. Nearby variants are also correlated, for which procedures ignoring the dependence between variants will inevitably produce redundant results. With a large number of variants genotyped in current genome-wide disease association studies, simultaneous multi-variant association mapping algorithms are strongly desired. We present a novel Bayesian method for automatic detection of multi-variant joint association in genome-wide case-control studies. Our method has improved power and specificity over existing tools. We fit a joint probabilistic model to the entire data and identify disease variants simultaneously. The method dynamically accounts for the strong linkage disequilibrium (LD) between variants. As a result, only the primary disease variants will be identified, with all secondary associations due to LD effects filtered out. Our method better pinpoints the disease variants with improved resolution. The method is also computationally efficient for genome-wide studies. When applied to a real dataset of inflammatory bowel disease (IBD) containing 401,473 variants in 4,720 individuals, our method detected all previously reported IBD loci in the same data, and recovered two missed loci. We further detected two novel inter-chromosome interactions. The first is between STAT3 and PARD6G, and the second is between DLG5 and an intergenic region at 5p14. We further validated the two interactions in an independent study.
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DOI：
10.1038/nrg2579
发表时间：
2009-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Cordell HJ
通讯作者：
Cordell HJ
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
5.8
作者：
Wu, Tong Tong;Chen, Yi Fang;Lange, Kenneth
通讯作者：
Lange, Kenneth
影响因子：
56.9
作者：
Duerr, Richard H.;Taylor, Kent D.;Cho, Judy H.
通讯作者：
Cho, Judy H.