Perceptual variation may represent an important aspect of genetic differences in human ingestive behavior (eg why we choose to eat and drink some foods and beverages but not others). This proposal represents a collaborative effort between investigators in chemosensory psychophysics, and molecular and quantitative behavioral genetics to examine how genetic variation in taste and pain receptors in the mouth may alter response to oral irritants that are commonly found in the food supply. Here, we propose a laboratory study to quantify the impact of variation in specific genes on the sensations that arise from capsaicin (the compound responsible for the heat of 'hot'peppers), piperine (the compound responsible for the burn of black pepper) and ethanol. Previously, we found capsaicin and piperine are bitter to some individuals but not others. Now, we ask if genetic variation in bitter taste genes can explain why. Analyses under Specific Aims 1-3 will determine if common polymorphisms (alternative forms of a gene) for the TRPV1 receptor predict differential response to the burning sensations from these irritants. Secondary aims test if certain variants of bitter taste genes can explain differences in the bitterness of these irritants. Important covariates include frequency of spicy food intake, personality factors (novelty seeking, and sensation seeking) and underlying differences in the intensity of oral sensations (supertasting). At the conclusion of this project, we will have produced a body of valuable data addressing the contribution of genetic polymorphisms on the burn and bitterness of oral irritants. Better understanding of the biology behind irritancy and bitterness will inform attempts to develop methods to block or mask these sensations and potentially remove palatability as a barrier to medication compliance. Proposed work may also provide new insight with respect to food choice behavior or causes of oral pathologies that involve burning sensations. PUBLIC HEALTH RELEVANCE: Taste is the main gatekeeper of ingestion: humans generally swallow what they like and reject what they don't, and what is liked may differ with genetics. This research examines whether the burning and bitterness from natural chemicals found in common spices are related to genetic differences in perception. Better understanding of the basic biology behind bitterness and irritancy will help us understand the dietary choices individuals make, and may help us tailor diets that improve health and wellness while remaining enjoyable to eat.