Sib-pair linkage analyses of alcoholism: Dichotomous and quantitative measures

We hypothesized that a quantitative alcoholism trait would have greater power than the Collaborative Study on the Genetics of Alcoholism (COGA) dichotomous alcoholism traits, ALDX1 and ALDX2, to detect putative alcoholism loci. To test this, we performed nonparametric sib-pair linkage analysis to screen 285 polymorphic autosomal markers for evidence of linkage to ALDX1, ALDX2, and a quantitative trait, QUANT, defined from the 11 COGA latent class variables. We also examined the effects on the analyses of including covariates (sex, age, and pack-years of smoking) and of transforming QUANT (log and square root). ALDX1 and ALDX2 showed the greatest evidence for linkage to markers on chromosome 1, by both the affected sib-pair and the Haseman-Elston tests. Regions of interest were also identified on chromosomes 4, 8, 16, and 17. QUANT showed little evidence for linkage to any chromosomal region, having no more significant results than were expected by chance. Including covariates or transforming QUANT had little effect on the analyses. A quantitative trait based on all 37 latent class variables, with each variable appropriately weighted, may have had more power than QUANT to detect genomic regions of relevance to alcoholism. (C) 1999 Wiley-Liss, Inc.