A GWAS of 1,897 cases and 1,932 controls from the COGA sample identified 15 SNPs with evidence of association at P < 10−5, but none were supported at P < 0.05 in two independent replication samples83. Reanalysis of this data set using an index of conduct disorder symptomatology identified four SNPs with genome-wide significant evidence for association, two in the C1q and tumor necrosis factor–related protein 7 (C1QTNF7) gene on chromosome 4p15.3 (ref. 84). In analysis of alcohol dependence symptoms in the 2,357 European American Molecular Genetics of Schizophrenia study control samples, the most significant intragenic SNP was in the potassium large conductance calcium-activated channel, subfamily M, alpha member 1 (KCNMA1, rs717207, 2.17 × 10−5) gene85. KCNMA1 is the human homolog of the slo-1 gene in Caenorhabditis elegans. Mutations in this gene in the worm lead to ethanol resistance and attenuation of the reductions in locomotion and egg-laying that normally follow exposure to ethanol86. The product of the slo-1 gene is known to limit excitatory neurotransmitter release in C. elegans87 and to be potentiated by ethanol88,89, suggesting that ethanol reduces (and slo-1 loss-of-function increases) excitatory neurotransmitter release and ethanol resistance.
