Evaluating associations of haplotypes with traits
Evaluating associations of haplotypes with traits
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DOI：
10.1002/gepi.20037
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发表时间：
2004-12-01
影响因子：
2.1
通讯作者：
Schaid, DJ
中科院分区：
文献类型：
--
作者：
Schaid, DJ
单倍型在高渗透性单基因疾病的研究中发挥了重要作用，最近的证据表明，人类基因组具有重组的热点和冷点，这表明基于单倍型的方法可能在研究常见的复杂性状中发挥关键作用。本文综述了利用单倍型研究人类性状遗传基础的动机，从生物学功能到单倍型的统计优势，再到连锁不平衡精细作图。本文综述了单倍型分析回归模型的最新进展，综述了现有的单倍型分析方法，并指出了它们的局限性和需要进一步研究的领域。回归模型提供了显著的优势，例如控制非遗传协变量的能力，可以对单倍型的影响进行建模，可以使用逐步选择来筛选解释大多数关联的标记子集，可以评估单倍型x环境相互作用，并且回归诊断得到了很好的发展。尽管有这些优势，目前的回归方法往往缺乏复杂的人口遗传学的角度所提供的合并和其他类似的方法。未来将回归方法与群体遗传模型联系起来的工作可能是有益的。Genet.流行病学(C)2004 Wiley-Liss，Inc.
Haplotypes have played a major role in the study of highly-penetrant single-gene disorders, and recent evidence that the human genome has hot-spots and cold-spots for recombination have suggested that haplotype-based methods may play a key role in the study of common complex traits. This report reviews the motivation of using haplotypes for the study of the genetic basis of human traits, ranging from biologic function, to statistical power advantages of haplotypes, to linkage disequilibrium fine-mapping. Recent developments of regression models for haplotype analyses are reviewed, offering a synthesis of current methods, as well as their limitations and areas that require further research. Regression models provide significant advantages, such as the ability to control for non-genetic covariates, the effects of the haplotypes can be modeled, step-wise selection can be used to screen for a subset of markers that explain most of the association, haplotype x environment interactions can be evaluated, and regression diagnostics are well developed. Despite these strengths, the current regression methods tend to lack the sophisticated population genetic perspectives offered by coalescent and other similar approaches. Future work that links regression methods with population genetic models may prove beneficial. Genet. Epidemiol. (C) 2004 Wiley-Liss, Inc.