A distinctive (and annoying) symptom of COVID-19 is loss of smell, known as anosmia, which is often accompanied by loss of taste. The exact cause of COVID-19 induced anosmia isn’t entirely clear, but researchers at 23andMe used their massive consumer-collected genetic data to identify potential gene mutations or variants that put people at risk of eating bland food for weeks after contracting COVID-19.
23andMe is a household name. People send their spit to the company regularly, often eagerly awaiting new information about their ancestry. The company has genetic data from more than 10 million people at their fingertips, and they use it for more than tracking down ancestors. People can opt-in after submitting their DNA samples to be included in future studies. 23andMe used this massive consumer database to design GWAS studies for identifying potential gene variants associated with severe cases of COVID-19 and for symptoms like anosmia.
In an article published in Nature Genetics, the researchers reported that specific mutations in two genes expressed in the nose and implicated in smell put people at increased risk of anosmia when infected with COVID-19 (1).
“It demonstrates the potential discovery power of having large biobanks including phenotypes or questionnaires and genetic data,” said Andrew Johnson, a cardiovascular and genomics researcher at the National Heart, Lung, and Blood Institute who was not involved in this study. “[23andMe] can pretty rapidly push out a survey to tens of thousands, or even a million people and get a fairly large response in a short time. That’s something that would be much harder to do in a typical academic environment, so they are definitely having an impact on research.”
For this study, 23andMe emailed 6.7 million customers a survey about their experience with COVID-19, including questions about symptoms like anosmia. 1.3 million people completed the survey. Nearly 70,000 patients reported that they received a positive COVID-19 test; about 70 percent of those patients experience anosmia. Those who tested positive with COVID-19 were more likely to lose their sense of smell than those with no positive test who experienced other cold or flu-like symptoms, including a runny nose or fever.
When they matched the survey data to their genetic data, the researchers identified a single nucleotide polymorphism (SNP) in the UDP Glucuronosyltransferase Family 2 Member A1 and A2 (UGT2A1/A2) gene. UFT2A1/A2 is expressed in a tissue that runs along the top of the nasal cavity far behind the nostrils called the olfactory epithelium. This tissue holds olfactory receptor cells that have long, fibral cilia. When a smell enters the nose, these cells sense it and send a signal to the brain to register the smell. Damage to these cilia often causes anosmia; this damage is what many scientists believe causes anosmia in COVID-19 patients.
Even though the results make biological sense, Johnson and Heping Zhang, a biostatistician from Yale School of Public Health who was not involved in this study, commented that the study design is handicapped by the nature of the consumer-collected data.“With GWAS studies, it’s often not easy to know what the causal gene is,” said Johnson. “It seems like there’s a plausible cellular tissue specific tie there that makes this likely to be a true association that has a biological basis.”
“If you just get whatever samples are available for your convenience, then you will not be able to consider how you define the outcomes you are trying to study,” said Zhang. “Loss of smell is a very subjective term, particularly when asking people to recall after they had COVID. How much did you lose?”
According to Zhang, a follow up study that recruits patients with ongoing COVID-19 infection and better defines the parameters for measuring loss of smell and taste would lend more confidence to the conclusions.
Adam Auton, the vice president of human genetics at 23andMe and the senior author of the study, said that the convenient access that 23andMe scientists have to genetic data and patients equips them to tackle questions others cannot.
“Using this survey-data paradigm, you’re able to collect biological insights that otherwise would be extremely difficult to understand. I don’t know of any other paradigm where you would be able to get funding to go out and do a large-scale study to really understand why people are losing their sense of smell,” said Auton.
Johnson commented that the association is “biologically interesting, but not clinically interesting,” which further demonstrates the potential for 23andMe to conduct exploratory studies that others may not have the time or funding for.
It demonstrates the potential discovery power of having large biobanks including phenotypes or questionnaires and genetic data.
- Andrew Johnson, National Heart, Lung, and Blood Institute
Auton likes that this study strategy allows study participants to be involved in more than one study at once and to be more actively involved in the process as the study is conducted and completed. Patients learn if they have or do not have any variant found in a study they participate in.
“When I’ve consented to research studies when I visited my doctor and things like that, I just sign a form, and then it disappears off into the ether. I’m confident these medical professionals are doing really great research and really great scientific discovery, but you lose the link,” said Auton. “We believe that people are in charge of their own destinies and how their information is being used for these types of studies. It makes people feel like they are participants as opposed to research subjects.”
In the end, Auton hopes that the GWAS studies he leads at 23andMe will not only help people become participants in research, but also provide researchers the leads they need to understand COVID-19 at the bench and in the clinic.
“We’re very interested in understanding how genetics can inform us about the underlying biology of various diseases and then asking the question that, if given that we understand the biology, are there opportunities for making therapeutic interventions in preventing or curing certain diseases?” said Auton. “Our paradigm is get the data out and get it published to contribute to large-scale research efforts that are going on in COVID.”
Shelton, J.F. et al. The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste. Nat Gen (2022).