A Mendelian trait for olfactory sensitivity affects odor experience and food selection.

Humans vary in acuity to many odors [1-4], with variation within olfactory receptor (OR) genes contributing to these differences [5-9]. How such variation also affects odor experience and food selection remains uncertain [10], given that such effects occur for taste [11-15]. Here we investigate ß-ionone, which shows extreme sensitivity differences [4, 16, 17]. ß-ionone is a key aroma in foods and beverages [18-21] and is added to products in order to give a pleasant floral note [22, 23]. Genome-wide and in vitro assays demonstrate rs6591536 as the causal variant for ß-ionone odor sensitivity. rs6591536 encodes a N183D substitution in the second extracellular loop of OR5A1 and explains >96% of the observed phenotypic variation, resembling a monogenic Mendelian trait. Individuals carrying genotypes for ß-ionone sensitivity can more easily differentiate between food and beverage stimuli with and without added ß-ionone. Sensitive individuals typically describe ß-ionone in foods and beverages as "fragrant" and "floral," whereas less-sensitive individuals describe these stimuli differently. rs6591536 genotype also influences emotional associations and explains differences in food and product choices. These studies demonstrate that an OR variant that influences olfactory sensitivity can affect how people experience and respond to foods, beverages, and other products.

Identification of regions associated with variation in sensitivity to food-related odors in the human genome.

Humans vary in their ability to smell numerous odors [1-3], including those associated with food [4-6]. Odor sensitivity is heritable [7-11], with examples linking genetic variation for sensitivity to specific odors typically located near olfactory receptor (OR) genes [12-16]. However, with thousands of aromas and few deorphaned ORs [17, 18], there has been little progress toward linking variation at OR loci to odor sensitivity [19, 20]. We hypothesized that OR genes contain the variation that explains much of the differences in sensitivity for odors, paralleling the genetics of taste [21, 22], which affect the flavor experience of foods [23-25]. We employed a genome-wide association approach for ten food-related odors and identified genetic associations to sensitivity for 2-heptanone (p = 5.1 × 10(-8)), isobutyraldehyde (p = 6.4 × 10(-10)), ß-damascenone (p = 1.6 × 10(-7)), and ß-ionone (p = 1.4 × 10(-31)). Each locus is located in/near distinct clusters of OR genes. These findings increase the number of olfactory sensitivity loci to nine and demonstrate the importance of OR-associated variation in sensory acuity for food-related odors. Analysis of genotype frequencies across human populations implies that variation in sensitivity for these odors is widespread. Furthermore, each participant possessed one of many possible combinations of sensitivities for these odors, supporting the notion that everyone experiences their own unique "flavor world."