Robust LOD scores for variance component-based linkage analysis
Robust LOD scores for variance component-based linkage analysis
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DOI：
10.1002/1098-2272(2000)19:1
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发表时间：
2000-01-01
影响因子：
2.1
通讯作者：
Almasy, L
中科院分区：
文献类型：
--
作者：
Blangero, J;Williams, JT;Almasy, L
在数量性状的连锁分析中，目前广泛使用的是方差分量法。尽管这种方法有许多优点，但家系内性状分布的多变量正态分布这一基本假设的重要性尚未得到广泛研究。模拟研究表明，具有尖峰分布的性状产生的连锁检验统计量在幼稚分析时表现出过多的I型误差。我们推导出与Lod分数的预期渐近分布的偏差与数量性状的峰度和总遗传力之间的关系的解析公式。对于任何偏离正态分布和任何系谱结构的情况，简单的校正常数都会产生稳健的Lod评分，并有效地消除了在基于方差分量的连锁分析中由于基础概率模型的错误指定而导致的I型错误问题。吉内。埃皮米诺。19(附录1)：中八至中十四，2000年。(C)2000 Wiley-Liss，Inc.
The variance component method is now widely used for linkage analysis of quantitative traits. Although this approach offers many advantages, the importance of the underlying assumption of multivariate normality of the trait distribution within pedigrees has not been studied extensively. Simulation studies have shown that traits with leptokurtic distributions yield linkage test statistics that exhibit excessive Type I error when analyzed naively. We derive analytical formulae relating the deviation from the expected asymptotic distribution of the lod score to the kurtosis and total heritability of the quantitative trait. A simple correction constant yields a robust lod score for any deviation from normality and for any pedigree structure, and effectively eliminates the problem of inflated Type I error due to misspecification of the underlying probability model in variance component-based linkage analysis. Genet. Epidemiol. 19(Suppl 1):S8-S14, 2000. (C) 2000 Wiley-Liss, Inc.