When considered separately, linkage was found over the region containing CYP2E1 and SNPs from the gene were found to be associated with the SHAS score. If inclusion of the causal variant as a covariate in variance component analysis always reduces the residual LOD score to zero, we were unable to implicate a causal variant directly influencing the level of response to alcohol in the families studied. It is possible that an unidentified polymorphism nearby could play a causal role in the level of response to alcohol as the degree of signal reduction is largest in the marker closest to the linkage peak and then declines for markers farther away. Another possibility is that a single marker cannot account for the entire linkage signal because many markers in the region play a role in the response. Instead of a single polymorphism causing variation, combinations of polymorphisms across the region may work together to contribute to the variation seen in our dataset. Support from the heterogeneity LOD score calculation showing that all families showed evidence for linkage combined with the independently derived
