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23andMe Study Associates Gene Locus With COVID-19-Related Loss of Smell, Taste

COVID Loss of Smell

NEW YORK — A 23andMe research team has homed in on a genetic locus that may be linked to the loss of smell or taste experienced by some COVID-19 patients.

Loss of the sense of smell or taste is often one of the first symptoms of COVID-19, though the biological mechanism behind it is not clear. Following an online survey of 23andMe research participants that asked about their COVID-19 experience and symptoms, the researchers conducted a multi-ancestry genome-wide association study that identified a genetic locus near the UGT2A1 and UGT2A2 genes that was linked with the loss of smell or taste.

These two genes, as the researchers reported in Nature Genetics, are expressed in the olfactory epithelium and are involved in odorant metabolism.

"As far as we're aware, this finding is the first genetic link to this symptom and may provide insight into how the virus is interacting with our bodies," senior author Adam Auton, VP of human genetics at 23andMe, said in an email. "However, it is very much a first step; follow-up studies will be needed to understand the underlying biology."

The researchers amassed a cohort of nearly 70,000 individuals who tested positive for SARS-CoV-2 at some point, 68 percent of whom said they experienced a loss of smell or taste and 32 percent of whom said they did not. Female participants were more likely to experience such a loss than men, and it was also more common among younger participants and those of European ancestry.

The researchers conducted separate association studies for the five ancestry groups represented in their cohort before performing a multi-ancestry meta-analysis. They identified a locus on chromosome 4 associated with an 11 percent increased risk of smell or taste loss, noting that while the effect size of the risk allele was consistent across populations, most of the support for the association came from the European cohort.

Through a subsequent phenome-wide association study of the index SNP against about 1,300 phenotypes in the 23andMe database, the researchers uncovered four other phenotypes that were also associated with this genetic locus, two of which are linked to smell or taste: ice cream taste preference and tobacco use.

Also, four genes lie within 150 kilobases of the index SNP: UGT2A1, UGT2A2, UGT2B4, and SULT1B1. UGT2A1 and UGT2A2 are not only the closest genes to the index SNP, which falls in an intron of the overlapping genes, but also the most biologically plausible. Both belong to a family of uridine diphosphate glycosyltransferases, enzymes that are expressed in the olfactory epithelium and involved in eliminating the odorants that bind to olfactory receptors.

The findings suggest that UGT2A1 or UGT2A2 might have a role — though still unclear — in the process leading to the loss of smell or taste among COVID-19 patients.

Auton added that numerous factors, such as how sensitive patients' senses were prior to infection and the severity of their infection, likely affect the loss of smell or taste. "In this study, we have been able to show for the first time that an individual's genetics likely plays a role as well," he said.

The study has limitations, as it relies on self-reporting and cannot distinguish between smell and taste, which the survey question combined, the researchers noted. It further is biased toward individuals of European ancestry.