Alcoholism is a complex disease with potentially many genetic influences. Investigators have tried to minimize heterogeneity by choosing a narrowly defined phenotype such as the level of response to alcohol that was measured with the SHAS score in this study. Significant evidence for linkage to 10qter was observed for the SHAS score in subjects from an alcohol challenge only after the removal of one family that retrospectively should not have been included in the analysis. After linkage was found at the end of chromosome 10, several SNPs genotyped in CYP2E1 were associated through logistic regression with the level of response to alcohol as reported by the SHAS score. Copy number did not appear to affect the SHAS score even though copy number differences were found between individuals across the CYP2E1 gene.
