The study of largest genome-wide association

Immunogenetics: Open access journal focuses on the genetic research areas of autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease, diabetes mellitus type 1, systemic lupus erythematous, etc. Articles on genetics of cell interaction with immune system, immune response to transplantation, immune based therapies for treatment of cancers, antigenic phylogeny of alleles, alloantigens are also welcome.

Researchers have known that people perceive odors based on olfactory receptors encoded by 855 olfactory genes. But about half of those genes in people are thought to lack function, leaving us with a relatively small repertoire of about 400 olfactory genes. The reason humans have lost so many olfactory genes has remained mysterious. It is also not well understood how variation in these genes might influence differences among people in their sense of smell.

Their search turned up variants in three genes or genetic loci of interest, which they were able to confirm in a separate sample of 2,204 Icelanders. One of them is in a non-canonical olfactory receptor gene called trace amine-associated receptor 5 (TAAR5). The TAAR5 variant affects perception of fish odor containing trimethylamine, a compound found in rotten and fermented fish, as well as other animal odors and various bodily secretions. In the smell tests, people with a particular variant of this gene were more likely to not smell anything when presented with the fish odor or to use descriptors for it that were neutral or positive and not seafood related, such as "potatoes," "caramel," and "rose." The findings are the first to show an important role for this gene in people.

Carriers of the variant find the fish odor less intense, less unpleasant, and are less likely to name it accurately. There is a lot of animal research on TAAR5 in relation to its role in hard-wired aversive responses to trimethylamine.

The other two discoveries were found in more typical and common olfactory gene variants. They influenced an individual's ability to name licorice and cinnamon odors. They also influenced the intensity and pleasantness associated with those odors.

The cinnamon variant influenced the perception of trans-cinnamaldehyde, the major ingredient in both Chinese and Ceylon cinnamon. Carriers of the variant can name the cinnamon odor more accurately.

Overall, the findings show that variation in olfactory genes influences odor perception in humans, while humans have fewer olfactory genes compared to other species, some of the genetic variation that people do carry makes them more sensitive to particular smells such as licorice or cinnamon, not less.

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Robert Solomon
Managing Editor
Immunogenetics: open access