Odds ratio based multifactor-dimensionality reduction method for detecting gene-gene interactions
Odds ratio based multifactor-dimensionality reduction method for detecting gene-gene interactions
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DOI：
10.1093/bioinformatics/btl557
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发表时间：
2007-01-01
期刊：
影响因子：
5.8
通讯作者：
Park, Taesung
中科院分区：
文献类型：
--
作者：
Chung, Yujin;Lee, Seung Yeoun;Park, Taesung
动机：在遗传关联研究中，增加对常见复杂多因素疾病易感的基因的鉴定和表征是一项艰巨的任务。 Ritchie等人提出并实施了多因素维度降低（MDR）方法。 （2001）确定与特定疾病相关的多焦基因型和离散环境因素的组合。但是，原始MDR方法基于对病例和对照组的比例的简单比较，以临时方式将多焦点基因型的组合分为高风险和低风险组。因此，当基因型组合中的病例和对照组的比率与整个数据中的情况相似，或者当病例和对照组较小时，MDR方法容易出现误差和负误差。因此，我们提出了基于赔率比率的多因素维度降低（或MDR）方法，该方法将优势比用作疾病风险的新定量量度衡量。种族：虽然原始的MDR方法提供了一种简单的风险二进制量度，但MDR方法提供优势比不仅是风险的定量度量，而且还从最高风险到最低风险组的多焦点组合订购。此外，或MDR方法为每个多焦点组合的优势比提供了一个置信区间，这在将其重要性视为危险因素方面非常有用。使用从CDC慢性疲劳综合征研究小组获得的数据集说明了提出的或MDR方法。
Motivation: The identification and characterization of genes that increase the susceptibility to common complex multifactorial diseases is a challenging task in genetic association studies. The multifactor dimensionality reduction (MDR) method has been proposed and implemented by Ritchie et al. (2001) to identify the combinations of multilocus genotypes and discrete environmental factors that are associated with a particular disease. However, the original MDR method classifies the combination of multilocus genotypes into high-risk and low-risk groups in an ad hoc manner based on a simple comparison of the ratios of the number of cases and controls. Hence, the MDR approach is prone to false positive and negative errors when the ratio of the number of cases and controls in a combination of genotypes is similar to that in the entire data, or when both the number of cases and controls is small. Hence, we propose the odds ratio based multifactor dimensionality reduction (OR MDR) method that uses the odds ratio as a new quantitative measure of disease risk.Results: While the original MDR method provides a simple binary measure of risk, the OR MDR method provides not only the odds ratio as a quantitative measure of risk but also the ordering of the multilocus combinations from the highest risk to lowest risk groups. Furthermore, the OR MDR method provides a confidence interval for the odds ratio for each multilocus combination, which is extremely informative in judging its importance as a risk factor. The proposed OR MDR method is illustrated using the dataset obtained from the CDC Chronic Fatigue Syndrome Research Group.