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Comparison of prospective and retrospective methods for haplotype inference in case-control studies
被引:64
|作者:
Satten, GA
Epstein, MP
机构:
[1] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA
[2] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA
关键词:
case-control study;
haplotype;
E-M algorithm;
ECM algorithm;
D O I:
10.1002/gepi.20020
中图分类号:
Q3 [遗传学];
学科分类号:
071007 ;
090102 ;
摘要:
We compare bias and power of three methods for haplotype inference on disease risk using unphased genotype data from a case-control study. We examine the prospective score test of Schaid et al. ([2002] Am. J. Hum. Genet 70:425-434), a novel modification of the prospective estimating equations of Zhao et al. ([2003] Am. J. Hum. Genet. 72:1231-1250) and the retrospective likelihood of Epstein and Satten ([2003] Am. J. Hum. Genet. 73:1316-1329). We find that all three approaches are roughly comparable when the haplotype effect on disease odds follows a multiplicative model. However, for dominant and recessive models of haplotype effect, the retrospective-likelihood method has increased efficiency with respect to the prospective methods. As all three methods assume haplotype frequencies are in Hardy-Weinberg Equilibrium (HWE), we compare the robustness of each procedure to departures from HWE. We find the prospective methods are robust to departure from HWE, while the retrospective-likelihood method is biased for dominant and recessive models of haplotype effect. To remedy this limitation of the retrospective-likelihood method, we propose a modification that allows for a non-negative fixation index (common to all haplotype pairs) and show it dramatically reduces the bias of the retrospective likelihood when HWE is violated. Published 2004 Wiley-Liss, Inc.(dagger).
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页码:192 / 201
页数:10
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