Support for previously identified alcoholism susceptibility loci in a cohort selected for smoking behavior

Background: Alcohol consumption and alcoholism are heritable traits. Previous linkage analyses for alcoholism and related traits have identified several putative susceptibility loci. In this paper we use, for the first time, linkage analysis to search for alcoholism-related phenotypes in a family sample selected for smoking behavior. Methods: Genome-wide model free linkage analysis was conducted for a variety of phenotypes related to alcohol consumption in 158 nuclear families ascertained for having at least two first-degree relatives who smoked 100 or more cigarettes in their lifetime. The phenotypes included dichotomous, ordinal, and continuous traits. Because the traits were typically not normally distributed the QTL score statistic as implemented in Merlin was employed to deal with deviations from normality. Simulation analysis determined that the QTL score statistic is robust to deviations from normality. Results: Linkage analysis detected three loci, one on chromosome 2 and two on chromosome 4, with nominal significance (LOD score > 2.7). These loci appear to be in close proximity to loci reported in other studies. Conclusions: While these findings did not reach genome-wide significance (LOD >4.0 given multiple comparisons) we have confidence that genes in these regions affect alcohol consumption. Two of the three significant findings in this analysis have been reported previously as alcoholism susceptibility loci. Simulation analysis shows that the most widely replicated finding on chromosome 4 is strongly supported (p = 0.01) even with correction for multiple comparisons. These findings suggest that previously reported linkage results are robust to the effects of different approaches to sample ascertainment and definition.