Expectation maximization algorithm based haplotype relative risk (EM- HRR): Test of linkage disequilibrium using incomplete case-parents trios
Expectation maximization algorithm based haplotype relative risk (EM- HRR): Test of linkage disequilibrium using incomplete case-parents trios
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DOI：
10.1159/000085571
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发表时间：
2005-01-01
期刊：
影响因子：
1.8
通讯作者：
Cupples, LA
中科院分区：
文献类型：
--
作者：
Guo, CY;DeStefano, AL;Cupples, LA
单倍型相对风险(HRR)首先被提出[Falk等人，Ann Hum Genet 1987]，用来检验一个标记和一个可能的疾病基因座之间的连锁不平衡(LD)。在这种基于家庭的研究中，在人口混合的情况下，不会出现虚假的关联。在本文中，我们通过期望最大化(EM)算法将HRR扩展到适应不完整的三元组[Dempster等人，J R Stat Soc SerB，1977]。除了三联体和二联体(亲子对)，EM-HRR很容易包括没有父母基因信息的个体，这被排除在单亲传递/不平衡测试(1-TDT)之外[Sun等人，Am J Epidinool 1999]。由于EM-HRR的数据结构，传递的等位基因始终是可用的，无论缺失亲本基因型的数量有多少。由于样本量较大，计算机模拟表明，在Hardy-Weinberg EquiliBirum(HWE)下，EM-HRR在检测LD方面比1-TDT更有效。如果掺杂物不是极端的，EM-HRR仍然更强大。当存在较大程度的混合时，EM-HRR在缔合较强时的表现优于1-TDT，但在缔合较弱时不如1-TDT。我们通过在Framingham心脏研究中的应用来说明所提出的方法。版权所有(C)2005年S.Karger AG，巴塞尔。
The Haplotype Relative Risk (HRR) was first proposed [Falk et al., Ann Hum Genet 1987] to test for Linkage Disequilibrium (LD) between a marker and a putative disease locus using case-parent trios. Spurious association does not appear in such family-based studies under population admixture. In this paper, we extend the HRR to accommodate incomplete trios via the Expectation-Maximization (EM) algorithm [Dempster et al., J R Stat Soc Ser B, 1977]. In addition to triads and dyads (parent-offspring pair), the EM-HRR easily incorporates individuals with no parental genotype information available, which is excluded from the one parent Transmission/ Disequilibrium Test (1-TDT) [ Sun et al., Am J Epidemiol 1999]. Due to the data structure of EM-HRR, transmitted alleles are always available regardless of the number of missing parental genotypes. As a result of having a larger sample size, computer simulations reveal that the EM- HRR is more powerful in detecting LD than the 1-TDT in a population under Hardy-Weinberg Equilibirum (HWE). If admixture is not extreme, the EM-HRR remains more powerful. When a large degree of admixture exists, the EM-HRR performs better the 1-TDT when the association is strong, though not as well when the association is weak. We illustrate the proposed method with an application to the Framingham Heart Study. Copyright (c) 2005 S. Karger AG, Basel.