在基于家系的基因关联研究中考虑亲缘关系。
Accounting for relatedness in family based genetic association studies.
作者信息
McArdle P F, O'Connell J R, Pollin T I, Baumgarten M, Shuldiner A R, Peyser P A, Mitchell B D
机构信息
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
出版信息
Hum Hered. 2007;64(4):234-42. doi: 10.1159/000103861. Epub 2007 Jun 14.
OBJECTIVE
Assess the differences in point estimates, power and type 1 error rates when accounting for and ignoring family structure in genetic tests of association.
METHODS
We compare by simulation the performance of analytic models using variance components to account for family structure and regression models that ignore relatedness for a range of possible family based study designs (i.e., sib pairs vs. large sibships vs. nuclear families vs. extended families).
RESULTS
Our analyses indicate that effect size estimates and power are not significantly affected by ignoring family structure. Type 1 error rates increase when family structure is ignored, as density of family structures increases, and as trait heritability increases. For discrete traits with moderate levels of heritability and across many common sampling designs, type 1 error rates rise from a nominal 0.05 to 0.11.
CONCLUSION
Ignoring family structure may be useful in screening although it comes at a cost of a increased type 1 error rate, the magnitude of which depends on trait heritability and pedigree configuration.
目的
评估在基因关联测试中考虑和忽略家族结构时，点估计、检验效能和I型错误率的差异。
方法
我们通过模拟比较了使用方差成分来考虑家族结构的分析模型与忽略亲缘关系的回归模型在一系列基于家族的可能研究设计（即同胞对、大型同胞组、核心家庭、大家庭）中的表现。
结果
我们的分析表明，忽略家族结构对效应大小估计和检验效能没有显著影响。当忽略家族结构、家族结构密度增加以及性状遗传力增加时，I型错误率会升高。对于具有中等遗传力水平的离散性状以及许多常见抽样设计，I型错误率从名义上的0.05上升到0.11。
结论
忽略家族结构在筛查中可能有用，尽管其代价是I型错误率增加，增加幅度取决于性状遗传力和家系配置。
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