Our main association findings were for the quantitative alcohol-related traits, initial sensitivity to alcohol and age at onset of AD. Several markers in GAD1 showed significant associations, and the effects were stronger in males than in females. For the three markers in GAD1 (Table 3) that exhibited significant associations with initial sensitivity to alcohol for which the common allele is risk allele, we calculated genotype means of alcohol intake to reach subjective effect at the time of initial use. Individuals with homozygote common vs. rare alleles required mean drinks of 6.9 vs. 5.2 in males, and 5.6 vs. 4.6 in females to feel ethanol effects. Initial sensitivity to alcohol may be more related to acute response to ethanol. Animal studies have shown that acute response to ethanol results in increase of GABA release in the brain and requires more GAD to transfer glutamic acid to produce GABA. For age at onset of AD, marker rs1978340 in GAD1 gene exhibited significant association. Males with homozygote common vs. rare alleles had mean onset age of 26.3 vs. 22.6 years, while onset age was not differed by genotypes in females.
