Exact family-based association tests for biallelic data
Exact family-based association tests for biallelic data
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DOI：
10.1002/gepi.20088
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发表时间：
2005-11-01
影响因子：
2.1
通讯作者：
Corcoran, C
中科院分区：
文献类型：
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作者：
Schneiter, K;Laird, N;Corcoran, C
以家庭为基础的研究设计在寻找疾病表型和遗传标记之间的联系方面发挥了重要作用。与传统的病例对照方法不同，基于家庭的测试使用家庭内的数据来避免识别可能由人口混杂造成的虚假关联。已经提出了许多基于家庭的关联测试，以适应各种确定方案和缺失数据的模式。在这份报告中，我们描述了双等位基因数据的精确的基于家族的关联检验。具体地说，我们讨论了零假设“无关联且无关联”和“关联但无关联”的检验。这些测试在遗传和缺失模式的各种模型下都有效，利用了Rabinowitz和Laird[2000：hum hered 50：211-223]提出的程序，该程序为基于家庭的关联测试(FBAT)提供了统一的框架。在FBAT中实现的条件方法使得精确检验在概念上简单，但在计算上困难，因为我们条件所依据的最小充分统计没有传统的形式。当需要精确计算FBAT统计量的极值区域时，例如当研究设计需要多次比较调整时，精确的检验可能尤其关键。我们把这种精确的方法描述为一种有用的替代方法，并表明对双等位基因数据的精确检验对于隐性疾病模型可能是最有用的。
Family-based study designs have an important role in the search for association between disease phenotypes and genetic markers. Unlike traditional case-control methods, family-based tests use within-family data to avoid identification of spurious associations that may result from population admixture. Many family-based association tests have been proposed to accommodate a variety of ascertainment schemes and patterns of missing data. In this report, we describe exact family-based association tests for biallelic data. Specifically, we discuss test of the null hypotheses "no linkage and no association" and "linkage, but no association". These tests, which are valid under various models for inheritance and patterns of missingness, utilize the procedure proposed by Rabinowitz and Laird [2000: Hum Hered 50:211-223] that provides a unified framework for family based association testing (FBAT). The conditioning approach implemented in FBAT makes an exact test conceptually straightforward, but computationally difficult since the minimum sufficient statistics upon which we condition do not have a conventional form. An exact test may be especially critical when accurate computation of the extreme area of the FBAT statistic is needed, such as when the study design necessitates multiple comparisons adjustments. We describe the exact approach as a useful alternative to the aymptotic test and show that the exact tests for biallelic data may be most useful for the recessive disease model.