Mapping alcoholism genes using linkage/linkage disequilibrium analysis.

Using a recently developed semiparametric method for combined linkage/linkage-disequilibrium analysis, we analyzed the Collaborative Study on the Genetics of Alcoholism data subset developed for Genetic Analysis Workshop 11 (GAW11). This semiparametric approach estimates recombination fractions for linkage, marker log odds ratios for linkage-disequilibrium, their product for combined linkage/linkage-disequilibrium, and corresponding z-scores. We used two outcomes: alcohol dependence and "alcoholism-free" and a genome-wide significance level of 4.1 (which corresponds to a genome-wide lod score of 3.6). For the alcohol dependence outcome, we observed significant linkage signals at D1S1588-D1S1631, D1S547, D2S399, D2S425, D4S2361, D7S1796, and D7S1824. We also found significant linkage-disequilibrium signals at D1S547 and D7S1795. For the "alcoholism-free" outcome, we found significant linkage signals at D4S2457, D41651 (both flank ADH3), D11S2359, and D16S47 and significant linkage-disequilibrium signals at D4S2361, FABP2, D11S2359, D19S431 and D19S47-D19S198-D19S601.