Lake S L, Lyon H, Tantisira K, Silverman E K, Weiss S T, Laird N M, Schaid D J
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA.
Hum Hered. 2003;55(1):56-65. doi: 10.1159/000071811.
In the study of complex traits, the utility of linkage analysis and single marker association tests can be limited for researchers attempting to elucidate the complex interplay between a gene and environmental covariates. For these purposes, tests of gene-environment interactions are needed. In addition, recent studies have indicated that haplotypes, which are specific combinations of nucleotides on the same chromosome, may be more suitable as the unit of analysis for statistical tests than single genetic markers. The difficulty with this approach is that, in standard laboratory genotyping, haplotypes are often not directly observable. Instead, unphased marker phenotypes are collected. In this article, we present a method for estimating and testing haplotype-environment interactions when linkage phase is potentially ambiguous. The method builds on the work of Schaid et al. [2002] and is applicable to any trait that can be placed in the generalized linear model framework. Simulations were run to illustrate the salient features of the method. In addition, the method was used to test for haplotype-smoking exposure interaction with data from the Childhood Asthma Management Program.
在复杂性状的研究中，对于试图阐明基因与环境协变量之间复杂相互作用的研究人员而言，连锁分析和单标记关联检验的效用可能有限。为此，需要进行基因-环境相互作用的检验。此外，最近的研究表明，单倍型（即同一条染色体上核苷酸的特定组合）作为统计检验的分析单位可能比单个遗传标记更合适。这种方法的难点在于，在标准实验室基因分型中，单倍型往往无法直接观察到。取而代之的是，收集的是未分型的标记表型。在本文中，我们提出了一种在连锁相可能不明确时估计和检验单倍型-环境相互作用的方法。该方法基于沙伊德等人[2002年]的研究成果，适用于任何可纳入广义线性模型框架的性状。进行了模拟以阐明该方法的显著特征。此外，该方法还用于根据儿童哮喘管理项目的数据检验单倍型与吸烟暴露之间是否存在相互作用。
