Evidence for linkage and association to alcohol dependence on chromosome 19

An association study on markers showing suggestive evidence for linkage to severe alcoholism was performed on the Collaborative Study on the Genetics of Alcoholism (COGA) data set. Our linkage study was restricted to the auto somal markers on chromosomes 2, 3, 4, 13, and 19, with low homozygosity (be low 30%) and high identity-by-state sharing in affected sib pairs (ASPs). W e used a strict phenotype definition, only individuals diagnosed as affecte d both on the ALDX1 (COGA criterion) and ALDX2 (ICD-10) scales were used in the analyses. Linkage was assessed by excess identity-by-descent allele sh aring in ASPs. The strongest evidence of linkage was detected on chromosome 19, in particular at markers D19S49 (p < 0.0001) and D19S431 (p < 0.002). An association study of allele and haplotype data was then carried out on c hromosome 19 markers using affected-family-based controls. A haplotype defi ned by alleles at markers D19S49, D19S43, and D19S200 in chromosome 19 show s significant association (p < 0.003, odds ratio 2.82). Further, significan t differences were observed in the distribution of the harm avoidance subsc ale among genotypes defined by D19849 (p < 0.0001). These results provide e vidence for the existence of a locus in chromosome 19 potentially involved in alcohol dependence susceptibility. (C) 1999 Wiley-Liss, Inc.