Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans
Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans
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DOI：
10.1038/sj.gene.6364299
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发表时间：
2006-06-01
影响因子：
5
通讯作者：
Ritchie, M. D.
中科院分区：
文献类型：
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作者：
Brassat, D.;Motsinger, A. A.;Ritchie, M. D.
多发性硬化症(MS)是一种常见的中枢神经系统疾病，以炎症、髓鞘丢失、胶质增生、不同程度的轴突病理和进行性神经功能障碍为特征。多发性硬化症表现出许多区别复杂遗传疾病的特征，包括多基因遗传和环境暴露风险。在这里，我们使用了一种代表与炎症途径相关的34个基因的变异的高效多位点基因分型方法，在一个具有良好特征的非裔美国人病例对照MS数据集中探索基因-基因相互作用和疾病易感性。我们应用多因素降维(MDR)检验来检测上位性，确定了单IL4R(Q576R)和三IL4R(Q576R)、IL5RA(-80)、CD14(-260)基因座关联模型，预测MS风险的准确率为75%-76%(P<；0.01)。这些结果证明了探索主效应和基因-基因交互作用在复杂疾病研究中的重要性。
Multiple sclerosis (MS) is a common disease of the central nervous system characterized by inflammation, myelin loss, gliosis, varying degrees of axonal pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits many of the characteristics that distinguish complex genetic disorders including polygenic inheritance and environmental exposure risks. Here, we used a highly efficient multilocus genotyping assay representing variation in 34 genes associated with inflammatory pathways to explore gene-gene interactions and disease susceptibility in a well-characterized African-American case-control MS data set. We applied the multifactor dimensionality reduction (MDR) test to detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R), IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76% accuracy (P < 0.01). These results demonstrate the importance of exploring both main effects and gene-gene interactions in the study of complex diseases.