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23andMe Researchers Identify Genetic Risk Factor for Loss of Smell and Taste in COVID-19 Patients

This new knowledge about the human genome may lead to a new set of biomarkers and clinical laboratory tests for predisposition to this health condition

Researchers across the globe are working to understand why some people who become infected with the SARS-CoV-2 coronavirus experience loss of smell (anosmia) and taste (ageusia) often for months following recovery from COVID-19 infection.

Now, pathologists and medical laboratory managers will be interested to learn that scientists from DNA testing company 23andMe believe they have identified a genetic risk factor associated with the condition. The discovery could lead to a new set of biomarkers for predisposition to loss of taste or smell that could help experts develop improved precision medicine treatments for similar conditions.

The 23andMe researchers published their findings in the journal Nature Genetics, titled, “The UGT2A1/UGT2A2 Locus Is Associated with COVID-19-Related Loss of Smell or Taste.”

Are Genes Responsible for the Loss of Smell and Taste after COVID-19?

“How we get from infection to smell loss remains unclear,” Justin Turner, MD, PhD, told USA Today. Turner is Associate Professor of Otolaryngology-Head and Neck Surgery at Vanderbilt University.

“Early data suggests that supporting cells of the olfactory epithelium are the ones mostly being infected by the virus and presumably this leads to the death of the neurons themselves. But we don’t really know why and when that happens, and why it seems to preferentially happen in certain individuals,” he added.

To perform their study, the 23andMe researchers examined the genetic tests of 69,841 individuals who self-reported that they had received a positive COVID-19 test. 68% of those people stated that they had experienced either loss of smell or taste as part of their symptomology of the illness. All the participants in the survey reside in either the United States or the United Kingdom.

After contrasting the genetic differences between those who experienced loss of taste or smell as a symptom of COVID-19 and those who did not, the team discovered a region of the genome associated with a spot located near the UGT2A1 and UGT2A2 genes. These two genes are expressed within tissue in the nose and are involved in smell and the metabolization of odorants.

Adam Auton, PhD
“It was this really beautiful example of science where, starting with a large body of activated research participants who have done this 23andMe test, we were able to quickly gain biological insights into this disease that would otherwise be very difficult to do,” said geneticist Adam Auton, PhD (above), Vice President, Human Genetics at 23andMe and lead author of the study, in the USA Today article. If found to be accurate, the findings could lead to clinically-useful clinical laboratory tests and to development of improved precision medicine therapies for patients who are predisposed to the condition. (Photo copyright: 23andMe.)  

It’s unclear if or how UGT2A1 and UGT2A2 genes may be involved in the process that leads to loss of taste or smell, but the 23andMe researchers hypothesize the genes may play a role in the physiology of infected cells which leads to the impairments.

The team found that 72% of female respondents reported loss of taste or smell as a symptom of COVID-19, which was higher than the 61% of male respondents who reported the same symptoms. In addition, the respondents who reported loss of taste or smell were typically younger than those who did not report those symptoms and persons of East Asian or African American ancestry were significantly less likely to report those symptoms.

An earlier study, titled, “Growing Public Health Concerns of COVID-19 Chronic Olfactory Dysfunction,” which appeared in the journal JAMA Otolaryngology-Head and Neck Surgery, stated that six months after contracting COVID-19 as many as 1.6 million people in the US experienced either lingering changes to their ability to smell or a complete loss of that sense.

Helping Patients Understand Why They Were Affected

Experts believe 23andMe’s findings may help patients deal with loss of taste or smell after a COVID-19 infection and increase the chance of finding suitable treatments.

“It answers the question of ‘why me’ when it comes to taste and smell loss with COVID-19,” Danielle Reed, PhD, Associate Director, Monell Chemical Senses Center, told USA Today. “Some people have it and some do not. Inborn genetics may partially explain why.”

Earlier research suggested the loss of these senses was related to a failure to protect the sensory cells of the nose and tongue from the viral infection. But according to Reed, the 23andMe study findings suggest a different cause.

“The pathways that break down the chemicals that cause taste and smell in the first place might be over or underactive, reducing or distorting the ability to taste and smell,” she said.

The 23andMe researchers noted their study had a few limitations:

  • It was biased towards individuals of European ancestry and lacked a replication cohort.
  • It relied on self-reported cases and symptom status.
  • No distinction between the loss of taste or smell could be determined as they were combined in a single survey question, making it unclear whether their findings relate more strongly to one symptom or the other.

Currently, there is no clinical imperative to test people in advance to see if they have a genetic predisposition to loss of smell or taste after a COVID-19 infection.

Nevertheless, this new insight into the human genome demonstrates the ongoing pace at which researchers are teasing out useful knowledge about the functions of human DNA. That knowledge will be used to do two things: first, to develop relevant, clinically-useful clinical laboratory tests, and second, to develop therapies for treating people with these genetic predispositions should they experience negative health conditions due to those genetic sequences.

JP Schlingman

Related Information:

Genetic Risk Factor Found for COVID-19 Smell and Taste Loss, Researchers Say

The UGT2A1/UGT2A2 Locus is Associated with COVID-19-related Loss of Smell or Taste

Growing Public Health Concern of COVID-19 Chronic Olfactory Dysfunction

King’s College London Study Identifies Six Distinct ‘Types’ of COVID-19 Illness, Each with a Distinct ‘Cluster’ of Symptoms

Clinical Laboratory Testing of USS Theodore Roosevelt’s Crew During COVID-19 Outbreak Offers Insights into the Coronavirus’ Impact on Young Healthy Adults

Broad Institute/Massachusetts General Hospital Researchers Develop Multi-Gene Test That Identifies Those at High Risk for Developing Heart Disease and Four Other Potentially Deadly Conditions

Next step is to design Web portal offering low-cost ‘polygenic risk score’ to people willing to upload genetic data received from DNA testing companies such as 23andMe

Pathologists and other medical professionals have long predicted that multi-gene diagnostics tests which examine thousands of specific gene sequences might one day hold the key to assessing disease risk, diagnosing diseases, and guiding precision medicine treatment decisions. Now, a research team from the Broad Institute, Massachusetts General Hospital (MGH) and Harvard Medical School have brought that prediction closer to reality.

Their study, published last month in Nature Genetics, found that a genome analysis called polygenic risk scoring can identify individuals with a high risk of developing one of five potentially deadly diseases:

  • Coronary artery disease;
  • Atrial fibrillation;
  • Type 2 diabetes;
  • Inflammatory bowel disease; and,
  • Breast cancer.

Polygenic Scoring Predicts Risk of Disease Among General Population

To date, most genetic testing has been “single gene,” focusing on rare mutations in specific genes such as those causing sickle cell disease or cystic fibrosis. This latest research indicates that polygenic predictors could be used to discover heightened risk factors in a much larger portion of the general population, enabling early interventions to prevent disease before other warning signs appear. The ultimate goal of precision medicine.

“We’ve known for long time that there are people out there at high risk for disease based just on their overall genetic variation,” senior author Sekar Kathiresan, MD, co-Director of the Medical and Population Genetics Program at the Broad Institute, and Director, Center for Genomic Medicine at Massachusetts General Hospital, said in a Broad Institute news release. “Now, we’re able to measure that risk using genomic data in a meaningful way. From a public health perspective, we need to identify these higher-risk segments of the population, so we can provide appropriate care.”

“What I foresee is in five years, each person will know this risk number—this ‘polygenic risk score’—similar to the way each person knows his or her cholesterol,” Sekar Kathiresan, MD (above), Co-Director of the Medical and Population Genetics Program at the Broad Institute, and Director, Center for Genomic Medicine at Massachusetts General Hospital, told the Associated Press (AP). He went on to say a high-risk score could lead to people taking other steps to lower their overall risk for specific diseases, while a low-risk score “doesn’t give you a free pass” since an unhealthy lifestyle can lead to disease as well. (Photo copyright: Massachusetts General Hospital.)

The researchers conducted the study using data from more than 400,000 individuals in the United Kingdom Biobank. They created a risk score for coronary artery disease by looking for 6.6 million single-letter genetic changes that are more prevalent in people who have had early heart attacks. Of the individuals in the UK Biobank dataset, 8% were more than three times as likely to develop the disease compared to everyone else, based on their genetic variation.

In absolute terms, only 0.8% of individuals with the very lowest polygenic risk scores had coronary artery disease, compared to 11% for people with the highest scores, the Broad Institute news release stated.

“The results should be eye-opening for cardiologists,” Charles C. Hong, MD, PhD, Director of Cardiovascular Research at the University of Maryland School of Medicine, told the AP. “The only disappointment is that this score applies only to those with European ancestry, so I wonder if similar scores are in the works for the large majority of the world population that is not white.”

In its news release, the Broad Institute noted the need for additional studies to “optimize the algorithms for other ethnic groups.”

The Broad Institute’s results suggest, however, that as many as 25 million people in the United States may be at more than triple the normal risk for coronary artery disease. And millions more may be at similar elevated risk for the other conditions, based on genetic variations alone.

Reanalyzing Data from DNA Testing Companies

The researchers are building a website that would enable users to receive a low-cost polygenic risk score—such as calculating inherited risk score for many common diseases—by reanalyzing data users previously receive from DNA testing companies such as 23andMe.

Kathiresan told Forbes his goal is for the 17 million people who have used genotyping services to submit their data to the web portal he is building. He told the magazine he’s hoping “people will be able to get their polygenic scores for about as much as the cost of a cholesterol test.”

Some Experts Not Impressed with Broad Institute Study

But not all experts believe the Broad Institute/MGH/Harvard Medical School study deserves so much attention. Ali Torkamani, PhD, Director of Genomics and Genome Informatics at the Scripps Research Translational Institute, offered a tepid assessment of the Nature Genetics study.

In an article in GEN that noted polygenic risk scores were receiving “the type of attention reserved for groundbreaking science,” Torkamani said the recent news is “not particularly” a big leap forward in the field of polygenic risk prediction. He described the results as “not a methodological advance or even an unexpected result,” noting his own group had generated similar data for type 2 diabetes in their analysis of the UK dataset.

Nevertheless, Kathiresan is hopeful the study will advance disease treatment and prevention. “Ultimately, this is a new type of genetic risk factor,” he said in the news release. “We envision polygenic risk scores as a way to identify people at high or low risk for a disease, perhaps as early as birth, and then use that information to target interventions—either lifestyle modifications or treatments—to prevent disease.”

This latest research indicates healthcare providers could soon be incorporating polygenic risking scoring into routine clinical care. Not only would doing so mean another step forward in the advancement of precision medicine, but clinical laboratories and pathology groups also would have new tools to help diagnose disease and guide treatment decisions.

—Andrea Downing Peck

Related Information:

Genome-wide Polygenic Scores for Common Diseases Identify Individuals with Risk Equivalent to Monogenic Mutations

Predicting Risk for Common Deadly Diseases from Millions of Genetic Variants

Multigene Test May Find Risk for Heart Disease and More

A Harvard Scientist Thinks He Has a Gene Test for Heart Attack Risk. He Wants to Give It Away Free

Why Do Polygenic Risk Scores Get So Much Hype?

World’s Largest Genetic Study in Iceland Produced New Insights into Gene Function and Disease Predisposition that Could Lead to New Clinical Laboratory Tests

Researchers sequenced the entire genomes of 2,636 Icelanders and gained useful insights into how human genes evolve and mutate

Over the past 15 years, Iceland has managed to be at the forefront of genetic research tied to personalized medicine and new biomarkers for diagnostics and therapeutics. This is true because, as most pathologists know, Iceland has a small population that has seen little immigration over the past 1,000 years, along with a progressive government and business community.

The relatively closed society of Iceland makes it much easier to identify genetic sequences that contribute to different diseases. The latest example of such research findings comes after the genomes of 2,636 Icelanders were sequenced. In addition to this being the world’s largest-ever study of the genetic makeup of a single population, the findings suggest a strategy for analyzing the full-spectrum of genetic variation in a single population.


Expanded Knowledge about Human Metabolome Expected to Fuel Development of New Therapeutic Drugs and Medical Laboratory Tests

Pathologists and clinical laboratory professionals can expect to see new molecular test development as researchers develop new biomarkers in the wake of expanded knowledge of the genome-metabolome-diseasome correlates

One field of science that bears great potential for use in diagnostics and medical laboratory testing involves the human metabolome. Researchers are gaining more understanding of the genetic underpinnings of complex disease and drug response through metabolic pathways.

For example, scientists at the Wellcome Trust Sanger Institute (WTSI) in the United Kingdom have linked 145 genetic regions with more than 400 molecules involved in metabolism in human blood, a story in Genetic Engineering News recently reported. The resulting atlas of associations will enable identification of genes that could be targeted in the development of drugs and clinical laboratory test. (more…)

Sequencing Developers’ Unprecedented Success Drives More Ambitious Goals For Genomics X Prize

New Genomic X PRIZE goals/subjects accelerate the drive toward personalized medicine

Swift improvements to the accuracy, speed, and lower cost of rapid gene sequencing have caused the sponsors of the globally-known X PRIZE to revamp their offer of a $10 million award to a team that is first to achieve a defined milestone in whole human genome sequencing.

Pathologists and clinical laboratory managers will be interested to learn how, last month, the X PRIZE Foundation announced a number of major changes to the formerly-named Archon Genomics X PRIZE. Most significantly, competition sponsors changed the subject from 100 genomes from unspecified donors, to genomes from 100 healthy centenarians.