Dudbridge Frank
Department Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
Methods Mol Biol. 2011;713:119-27. doi: 10.1007/978-1-60327-416-6_9.
Family-based association methods are useful because they offer improved matching of controls to cases, with the result that they are not susceptible to confounding by population stratification. They also allow analysis of parent-of-origin effects and maternal-fetal interactions. The transmission/disequilibrium test (TDT) is a test of linkage and association that is equivalent to a matched case/control analysis, from which various extensions are possible. A logistic regression formulation leads to modifications for multiallelic markers, haplotypes, and quantitative traits. Some pitfalls are described, for the situations in which one parent is missing, genotyping errors have occurred, and haplotype phase is uncertain. The problem of testing association in general pedigrees is discussed, with particular reference to sib pairs without parents.
基于家系的关联方法很有用，因为它们能更好地将对照与病例进行匹配，结果是不易受到群体分层导致的混杂影响。它们还允许分析基因的亲本来源效应和母胎相互作用。传递/不平衡检验（TDT）是一种连锁和关联检验，等同于匹配病例/对照分析，在此基础上可以进行各种扩展。逻辑回归公式可用于多等位基因标记、单倍型和数量性状的修正。文中描述了一些陷阱，包括一方亲本缺失、发生基因分型错误以及单倍型相位不确定的情况。还讨论了在一般系谱中检验关联的问题，特别提及了没有父母的同胞对。
