Maximum-likelihood-binomial method for genetic model-free linkage analysis of quantitative traits in sibships

作者：Alexandre Alca�s, Laurent Abel · 发表于：Genetic Epidemiology · 年份：1999 · DOI：10.1002/(sici)1098-2272(1999)17:2<102::aid-gepi2>3.0.co;2-6 · 被引用次数：47 · 研究领域：Genetic Mapping and Diversity in Plants and Animals、Genetic and phenotypic traits in livestock、Genetics and Plant Breeding

Sib-pair linkage studies are widely used to investigate the genetic factors implicated in complex quantitative traits. To analyze these data, we propose a Maximum-Likelihood-Binomial (MLB) approach, which considers the sibship as a whole and relies on the idea of binomial distributions of parental alleles among offsprings. The method is based on the introduction of a latent binary variable capturing the linkage information between the observed quantitative trait and the marker, and the final likelihood can be expressed assuming a parametric distribution for the studied trait but also without any assumption on this distribution. The test for linkage is a simple likelihood ratio test involving a single parameter. The performances of the MLB method are assessed by a simulation study in different kinds of family samples. In the case of families with various sibship sizes, both MLB approaches (assuming or not a parametric distribution for the quantitative trait) provide very consistent results in terms of type I errors and yield power levels generally higher than those of the classical Haseman-Elston method. In the case of extremely discordant sib pairs, we analytically show that, for a common asymptotic type I error, the distribution-free MLB statistic is expected to be more powerful than the test proposed by Risch and Zhang [(1995) Science 268:1584-1589]. In samples including both extremely concordant and discordant sib-pairs, simulation studies show that the MLB approach is at ...