Nonparametric linkage analysis of alcohol dependence with chromosome 1 and 7 markers.

We analyzed 105 multiplex families from the Collaborative Study on the Genetics of Alcoholism (COGA) for markers on chromosome 1 (n = 20) and chromosome 7 (n = 19) with the GENEHUNTER program. On chromosome 1, three markers (D1S532, D1S1588, and D1S534) in single-point analysis and five markers in multipoint analysis (D1S532, D1S1588, D1S1675, D1S534, and D1S1595) showed a nonparametric linkage (NPL) p-value < 0.05. They mapped in two different but nearby regions, spanning, respectively, 18 cM (D1S532, D1S1588) and 19 cM (D1S1675, D1S534, and D1S1595) and separated by a 20-cM interval. The highest NPL score was obtained for D1S534 (NPL = 2.26, p = 0.013 for single-point analysis and NPL = 2.81, p = 0.0029, for multipoint analysis). The maximum NPL score on chromosome 7 was observed for D7S1793 (NPL = 1.72, p = 0.044 for single-point analysis and NPL = 2.02, p = 0.023 for multipoint analysis). The markers which showed NPL p-values < 0.05 on chromosome 1 (D1S532, D1S1588, D1S1675, D1S534, and D1S1595) and on chromosome 7 (D7S1793) were analyzed for association using the transmission/disequilibrium test. None of the alleles at these six loci showed a distorted transmission pattern. These data indicate that the two loci "suggestively" linked to alcohol dependence are either in linkage equilibrium with a susceptibility locus or are too far from the susceptibility locus to show disequilibrium, if present.