Natural variation on ChrI and ChrIV linked to locomotion activation in response to ethanol in C. elegans

Alcohol use disorder is a global problem, with 50% of the risk determined by genetics. The acute physiological response to alcohol is a reliable predictor of AUD risk. Identifying genes and pathways that modulate acute ethanol responses is essential to understanding the molecular basis of alcohol use disorder. Acute ethanol responses are conserved across species, including nematodes. Therefore, natural variation in Caenorhabditis elegans provides an opportunity to link wild alleles to acute ethanol response behaviors. Here, multi-parent recombinant inbred lines were behaviorally characterized in an ethanol response locomotion assay. Animals were continuously exposed to 0 mM, 200 mM, or 400 mM exogenous ethanol and tracked at 10, 30, and 50 minutes. Initial sensitivity, acute functional tolerance, and low concentration locomotor activation had narrow sense heritabilities of 0.28, 0.13, and 0.36, respectively, indicating that the observed phenotypic variance can be partly explained by additive genetics. QTL mapping identified two QTL for low concentration locomotor activation, which together explain 45.5% of the observed phenotypic variance in this population. The validation of these QTL using introgression lines and subsequent candidate prioritization will hopefully lead to the identification of genes that modulate low concentration locomotor activation in wild nematode populations.