Power comparisons between similarity-based multilocus association methods, logistic regression, and score tests for haplotypes.
Power comparisons between similarity-based multilocus association methods, logistic regression, and score tests for haplotypes.
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DOI：
10.1002/gepi.20364
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发表时间：
2009-04
影响因子：
2.1
通讯作者：
Schaid, Daniel J.
中科院分区：
文献类型：
--
作者：
Lin, Wan-Yu;Schaid, Daniel J.
最近，提出了用于多位点关联的基于基因组距离的回归（Am. J.哈姆。Genet. 79：792-806），其中基因座或单体型评分可用于测量遗传距离。虽然它允许各种措施的基因组相似性和同时分析多种表型，其权力相对于其他方法的病例对照分析是不为人所知的。我们比较了传统方法与这种新的基于距离的方法，无论是基因座评分和单倍型评分策略的力量。我们讨论了这些关联方法在以下五个方面的相对功效：（1）标记信息量;（2）标记数量;（3）因果等位基因频率;（4）最常见的高风险单倍型的优势;（5）因果单核苷酸多态性（SNP）及其侧翼标记之间的相关性。我们发现，基因座为基础的逻辑回归和单倍型的全球得分测试遭受功率损失时，许多标记被包括在分析中，由于许多自由度。相比之下，基于距离的方法不容易受到更多标记或更多单倍型的影响。一个基因型计数措施是更敏感的标记信息量和因果SNP及其侧翼标记之间的相关性。在检查了这五个属性对功效的影响后，我们发现，平均而言，使用双体型匹配度量的基于基因组距离的回归是我们比较的七种方法中最强大和最稳健的方法。
Recently, a genomic distance-based regression for multilocus associations was proposed ( Am. J. Hum. Genet. 79:792–806) in which either locus or haplotype scoring can be used to measure genetic distance. Although it allows various measures of genomic similarity and simultaneous analyses of multiple phenotypes, its power relative to other methods for case-control analyses is not well known. We compare the power of traditional methods with this new distance-based approach, for both locus-scoring and haplotype-scoring strategies. We discuss the relative power of these association methods with respect to five properties: (1) the marker informativity; (2) the number of markers; (3) the causal allele frequency; (4) the preponderance of the most common high-risk haplotype; (5) the correlation between the causal single-nucleotide polymorphism (SNP) and its flanking markers. We found that locus-based logistic regression and the global score test for haplotypes suffered from power loss when many markers were included in the analyses, due to many degrees of freedom. In contrast, the distance-based approach was not as vulnerable to more markers or more haplotypes. A genotype counting measure was more sensitive to the marker informativity and the correlation between the causal SNP and its flanking markers. After examining the impact of the five properties on power, we found that on average, the genomic distance-based regression that uses a matching measure for diplotypes was the most powerful and robust method among the seven methods we compared.
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