Human genetic association identified GPC5, a member of the glypican gene family, to be of statistical interest with a multiple-test–corrected FDR q-value of 0.082. We then moved to a Drosophila model system to obtain correlative evidence in an experimental system where mutations can be introduced and tested for their effect on ethanol-induced behaviors. The Drosophila results supported the mammalian genetic results by demonstrating that flies carrying mutant alleles of dally or dlp, the Drosophila homologs of mammalian glypicans, exhibit alterations in ethanol-induced locomotor activity, ethanol-induced sedation, and rapid tolerance to ethanol-induced sedation. Together, these results strongly implicate GPC5 as a contributor to ethanol response.
