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-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.
Durrieu
G
G
INSERM U358, Hôpital Saint-Louis, Paris, France.
Meunier
F
F
O'Connell
J
J
Martinez
M
M
Demenais
F
F
D000437:Alcoholism / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D018913:Event-Related Potentials, P300 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008957:Models, Genetic; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable; D018709:Statistics, Nonparametric
D005819:Genetic Markers