Genetic variation across the human olfactory receptor repertoire alters odor perception

Abstract

The human olfactory receptor repertoire is characterized by an abundance of genetic variation that affects receptor response, but the perceptual effects of this variation are unclear. To address this issue, we sequenced the OR repertoire in 332 individuals and examined the relationship between genetic variation and 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR frequently associated with odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. This more than doubles the published examples of this phenomenon. For eight of these 10 cases, reduced receptor function associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age and gender, we can explain between 10 and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in variation of olfactory perception.

Predicting Human Olfactory Perception from Activities of Odorant Receptors

“…More recently, the specific amino acid residues of OR5AN1 that are responsible for its high selectivity to musk-smelling chemicals have also been confirmed (Ahmed et al, 2018). These studies were possible owing to three types of information: (1) perceptual responses of humans, (2) the odorant receptors that detect the chemicals from heterologous expression systems, and (3) genetic studies (Trimmer et al, 2019). Obtaining this information is not trivial for reasons that include the difficulty of receptor deorphanization and that behavioral responses are known for only a fraction of the purported volatile space, owing to low throughput data collection with human volunteers.…”

Volatile Phenols—Important Contributors to the Aroma of Plant-Derived Foods

“…It is clear that these olfactory receptors (ORs) play a key role in odorant perception. Up to now, for approximately 40% of the 400 functional human ORs, agonists have been identified in bioassays [ 18 ]. Research on structure–activity relationships of the human OR10G receptors has shown that these receptors are broadly tuned to volatile phenols ( Table 1 ) [ 19 ].…”

Individual Differences in Thresholds and Consumer Preferences for Rotundone Added to Red Wine

“…Odor percepts arise from the pattern of activation across these different receptors (see [ 9 ] for a review). The specific receptors present in an individual’s nose and the number of each type of receptor are genetically determined, resulting in individual differences in odor perception [ 10 , 11 ]. That is, some individuals may lack a functional variant of a certain receptor and be unable to smell molecules that would bind to that receptor, while still having an otherwise normal sense of smell.…”