Case-control single-marker and haplotypic association analysis of pedigree data
Case-control single-marker and haplotypic association analysis of pedigree data
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DOI：
10.1002/gepi.20051
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发表时间：
2005-02-01
影响因子：
2.1
通讯作者：
Wagner, MJ
中科院分区：
文献类型：
--
作者：
Browning, SR;Briley, JD;Wagner, MJ
收集用于连锁研究的相关个体可用于病例-对照连锁不平衡分析，前提是考虑个体之间由于遗传同一性（IBD）共享的相关性。我们通过计算每个个体的权重来解释这些相关性。权重用于构建复合似然，其被迭代地最大化以形成单标记和单倍型关联的似然比检验。该方法的规模以及增加系谱的大小和复杂性，并适用于常染色体和X染色体。我们应用该方法分析2型糖尿病和PPAR-gamma基因单核苷酸多态性标记之间的关联。仿真数据用于检验检验的有效性和检验功效。相关病例的分析比基于人群的病例的分析具有更好的功效，因为与基于人群的病例中的这些等位基因的频率相比，具有多个病例的家系中的疾病易感性等位基因的频率增加。此外，利用谱系中的所有病例而不是每个谱系仅一个病例，通过增加有效样本量来提高功效。我们证明，我们的方法具有至少与几种竞争方法一样大的能力，同时在处理缺失数据和进行单倍型分析的能力方面具有优势。(C)2004 Wiley-Liss，Inc.
Related individuals collected for use in linkage studies may be used in case-control linkage disequilibrium analysis, provided one takes into account correlations between individuals due to identity-by-descent (IBD) sharing. We account for these correlations by calculating a weight for each individual. The weights are used in constructing a composite likelihood, which is maximized iteratively to form likelihood ratio tests for single-marker and haplotypic associations. The method scales well with increasing pedigree size and complexity, and is applicable to both autosomal and X chromosomes. We apply the approach to an analysis of association between type 2 diabetes and single-nucleotide polymorphism markers in the PPAR-gamma gene. Simulated data are used to check validity of the test and examine power. Analysis of related cases has better power than analysis of population-based cases because of the increased frequencies of disease-susceptibility alleles in pedigrees with multiple cases compared to the frequencies of these alleles in population-based cases. Also, utilizing all cases in a pedigree rather than just one per pedigree improves power by increasing the effective sample size. We demonstrate that our method has power at least as great as that of several competing methods, while offering advantages in the ability to handle missing data and perform haplotypic analysis. (C) 2004 Wiley-Liss, Inc.