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

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-linkag e (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 thr ee cases but to higher p-values in all others. Investigation of these discr epancies shows that assumptions (normality and homoscedasticity of the erro r term) of H-E least-squares regression method are not verified. A robust e stimator of slope parameters without assuming any distribution function for the linear model error terms increases the p-values and reduces the differ ence between H-E and CSL results. Alternatively, the CSL approach may lack power when multiple genes with small effects are involved. (C) 1999 Wiley-L iss, Inc.