Why Do Some People Dislike the Smell of Fish While Others Do Not Mind It?

The same fish odor makes some people grimace while barely bothering others. Can familiarity with eating fish alone explain that difference? Before anyone calls an odor “fish,” the information received by the nose itself may differ.

In 2020, Rosa S. Gisladottir and colleagues examined genetic information and responses from 11,326 people in Iceland who actually smelled the odors. They found a variant in a receptor called TAAR5 associated with fish-odor perception, as well as regions linked to the perception of licorice and cinnamon. The study looked beyond how strong or weak an odor seemed. It investigated whether receptor differences were also linked to pleasantness and unpleasantness, and even to the names people gave an odor.

Smelling Six Odors and Reporting Their Names, Intensity, and Pleasantness

The researchers used pen-shaped devices releasing odors of fish, licorice, cinnamon, lemon, peppermint, and banana. The experimenter removed the cap and presented each device approximately 2 cm from the participant’s nose for three seconds. Participants named the odor, in one word if possible, and then rated its intensity and pleasantness on separate seven-point scales. This was a task of recalling a name independently, not choosing from a list of answers.

The researchers first explored associations between genetic differences and odor assessments in data from 9,122 people, then tested the main findings in a separate group of 2,204. The total of 11,326 participants ranged from 18 to 96 years old. Analyses accounted for factors such as age and sex, and also adjusted for differences between people inclined to give high ratings and those inclined to give low ones.

The “licorice” stimulus consisted primarily of trans-anethole, and “cinnamon” of trans-cinnamaldehyde. “Fish,” however, was not fish itself, but a mixed stimulus containing mainly trimethylamine, or TMA, which has a fish-like odor, together with small quantities of sulfur compounds. This distinction matters to avoid extending the findings too broadly to fish dishes in general.

A TAAR5 Variant Was Associated with Lower Perceived Fish-Odor Intensity

The variant identified for fish odor was called p.Ser95Pro in the receptor TAAR5. People carrying this variant tended to rate the experimental fish odor as less intense. The association was confirmed not only in the initial group but also in the separate group studied later.

In the analysis combining both groups, the variant was also associated with greater difficulty identifying the fish odor and with slightly less unpleasantness. Carriers were also relatively more likely to report smelling nothing. However, not everyone carrying the variant failed to perceive the fish odor, and the statistical strength of the intensity association differed from that of the pleasantness association.

The 2.2% frequency reported for this variant in the paper is the frequency of the genetic allele in Iceland, not the percentage of people who cannot smell fish. Nor was this a study that determined who likes or dislikes fish dishes from the presence or absence of the variant.

Answers Other Than “Fish” Also Reflect Differences in Perception

Closer examination of the free responses showed that carriers were less likely to use words suggesting fermented fish, and tended instead to name neutral or pleasant things unrelated to seafood. The authors consider that differences in aversion to fish odor appeared not only in pleasantness ratings but also in the words people chose.

The important point is not to treat a different name simply as a failure to know the word. If a stimulus is perceived differently, what it brings to mind may also change. However, these results alone cannot distinguish whether the odor is less unpleasant because it seems weaker or whether receptor differences are involved in aversion itself.

Earlier research had established that TAAR5 responds to TMA, and the location of the variant in this study was also one that could alter receptor function. The authors consider it a strong candidate for a causal variant, but how it changes the receptor’s shape or its placement on the cell surface remains a question for future functional experiments.

Licorice and Cinnamon Also Showed Associations with Stronger Perception and Easier Naming

For licorice, a region including a variant in the receptor gene OR6C70 was associated with stronger perceived intensity and easier naming. For cinnamon, too, a variant near another cluster of olfactory receptor genes was associated with easier naming. These associations were replicated in the separate group of 2,204 people, and when both groups were combined, an association with stronger cinnamon perception was also observed.

However, the licorice region contains many variants that tend to be inherited together, so OR6C70 alone cannot be singled out as the cause. Nor has the function of a particular receptor been established for cinnamon. The receptor candidates suggested by the authors need to be distinguished from the genetic associations established in this study.

Variants in both regions were also associated with weaker perception of lemon. The combination of stronger licorice or cinnamon perception and weaker lemon perception shows how difficult it is to describe someone’s sense of smell with a single measure of “a good nose.” The authors consider this consistent with a system in which one receptor can respond to multiple molecules and each odor is detected through a combination of receptors.

Receptors Are Also Involved in the Ability to Name Odors

Sometimes an odor seems familiar, yet its name will not come to mind. This difficulty relates to memory, language, and opportunities to encounter it in everyday life. The study showed that, alongside these factors, genetic differences in olfactory receptors also appear in naming-task performance.

For cinnamon in particular, the ability to give the name showed a clearer association with genetic differences than perceived intensity did. The authors consider that a free odor-naming task could be a useful measure for detecting receptor differences.

The pathway is not yet known. The authors leave open both the possibility that stronger or weaker perception changes how easy an odor is to name, and the possibility that receptor differences affect neural connections. This does not mean that a “gene that determines vocabulary” has been discovered.

Olfactory Variation Cannot Be Explained Only as “Decline”

The authors emphasize in their conclusion that genetic changes did not only point toward diminished olfactory function. Alongside an association with weaker fish-odor perception, there were associations with greater intensity or better naming performance for licorice and cinnamon. This adds another dimension to the view that diverse variants in olfactory receptors simply represent an accumulation of losses of function.

Because the frequencies of these variants also differ geographically, the authors discuss the possibility that natural selection has shaped olfactory diversity. However, they did not directly test how a variant might have conferred an advantage in a particular food culture. Regional allele frequencies cannot be used to explain people’s food preferences or rank their olfactory abilities as a whole.

Limitations Remain Even in a Large Study

Participants belonged to a research cohort in Iceland, and recruitment was designed to include more people who had inherited rare variants from both parents. They were not a randomly selected miniature of the world’s population. Odor naming also involves foods and words familiar in the local culture.

In addition, the main associations discovered initially and confirmed in a separate group were at a different stage of validation from the pleasantness and cross-odor associations subsequently examined in the combined sample. Finding associations in a large number of people does not make all of them equally strong evidence.

Finding fish odor less unpleasant does not indicate whether food is safe. This experiment did not assess food freshness or health effects; it measured responses to a mixed stimulus containing TMA. Changes in food preferences through familiarity and culture also need to be investigated separately from how a stimulus itself is perceived.

Summary

The study of 11,326 people showed that genetic differences in TAAR5 were involved in differences in fish-odor intensity, aversion, and the words used to describe it. Together with the licorice and cinnamon findings, the results indicate that individual receptor differences appear not only in “how strong it seems” but also in what the odor is perceived to be. This offers a way to investigate the relationship between smell and language through how information is received in the nose.

An important conclusion drawn by the authors is that diversity in olfactory receptors is associated not only with reduced sensitivity, but also with greater intensity and improved naming for particular odors. However, steps remain to be established in the pathway from genetic association to receptor function, aversion, and naming. This large study suggests that neither familiarity and preference alone nor genes alone can fully explain different responses to the same odor.

References
Gisladottir RS, Ivarsdottir EV, Helgason A, et al. (2020). Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming. Current Biology, 30(23), 4643–4653.e3. Read the original paper
Rights notice: The original paper is available under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0).