Detection of quantitative trait loci associated with alcohol-dependence: Use of model-free sib-pair method and combined segregation-linkage analysis based on regressive models

Abstract : Two linkage methods were used to detect loci underlying neurophysiological measures associated with alcohol dependence 1) the Haseman-Elston (H-E) sib pair method for genome-wide search, and 2) the combined segregation-linkage (CSL), based on regressive models, to confirm positive linkages found by the genome screening. Among 14 linkage results that were significant at the 0.5% level using H-E, the CSL method leads to similar p-values in only three cases but to higher p-values in all others. Investigation of these discrepancies shows that assumptions (normality and homoscedasticity of the error term) of H-E least-squares regression method are not verified. A robust estimator of slope parameters without assuming any distribution function for the linear model error terms increases the p-values and reduces the difference between H-E and CSL results. Alternatively, the CSL approach may lack power when multiple genes with small effects are involved.
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https://hal.archives-ouvertes.fr/hal-00906803
Contributor : Gilles Durrieu <>
Submitted on : Wednesday, November 20, 2013 - 1:07:40 PM
Last modification on : Saturday, May 18, 2019 - 7:44:02 PM

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Gilles Durrieu, Flavie Meunier, Jeffrey R O'Connell, Maria Martinez, Florence Demenais. Detection of quantitative trait loci associated with alcohol-dependence: Use of model-free sib-pair method and combined segregation-linkage analysis based on regressive models. Genetic Epidemiology, Wiley, 1999, 17, pp.145-150. ⟨hal-00906803⟩

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