Molly Campbell
is a science writer and editor for the online news publication
Technology Networks. She produces content for and manages
the Genomics, Proteomics, Metabolomics and Biopharma communities.
Her new video series, Teach Me in 10, challenges scientists
to communicate their research or a scientific concept in less
than 10 minutes.
The personal genomics
and biotechnology company 23andMe is perhaps best known for
its home DNA testing kits, whereby consumers can learn about
their genetic make-up or ancestry.
However, after the
COVID-19 outbreak was declared a global pandemic, the company
switched gears and looked to see how their gene testing services
could offer a helping hand in understanding the disease’s
pathophysiology.
One aspect of COVID-19
that has puzzled scientists and clinicians alike is why, when
infected with SARS-CoV-2, do some patients display mild to moderate
symptoms (or no symptoms at all), whereas other patients develop
severe symptoms that can prove fatal?
23andMe questioned
whether genetics could play a role here. Why? Well, we know
that specific genetic variants can render individuals as less
or more susceptible to developing other infectious diseases
such as HIV, malaria and norovirus. 23andMe has contributed
to this field of research, publishing a study in 2017 which
identified almost 60 genetic variants associated with susceptibility
to one of 17 infectious diseases.
To cause infection,
SARS-CoV-2 must enter cells, and does so by attaching to a human
protein known as ACE2. Genetic variants can exist in and around
the gene that encodes this protein, which might impact exactly
how much of the protein is produced, or how it functions. It's
therefore plausible to consider the fact that genetic variation
might play a role in COVID-19 severity. But, a large-scale study
in a range of populations would be required to gather enough
data to prove or negate this.
In early April,
23andMe announced its plans to conduct such a study utilizing
its large bank of genetic data from its customers who had consented
to their information being used for research purposes.
The study takes
the form of a GWAS, or genome-wide association study, whereby
the aim is to identify genetic variants in an individual's genome
that is associated with differences in COVID-19 severity. The
announcement of the research study was received well, with over
half a million participants enrolling within the first few weeks.
As such, on May
13, 23andMe announced that it was expanding the project and
opening enrolment to individuals that had been hospitalized
with severe COVID-19 but were not 23andMe customers.
“Opening up
the research to individuals with more severe symptoms will increase
our power to learn how genes play a role in the severity of
this disease,” said Joyce Tung, Vice President of Research.
ANALYZING GENETIC
ASSOCIATION
Fast-forward to
the present day, and 23andMe are sharing their preliminary results,
which are certainly interesting. The data seems to lend further
evidence to the notion that an individual's blood type, determined
by the ABO gene, is associated with differences in COVID-19
susceptibility.
After analyzing
over 750,000 individuals' data, the company states that when
comparing the research participants who reported that they had
tested positive for COVID-19 to those who tested negative, variants
in the ABO gene were associated with a lower risk.
Of course, it is
important to note here that this is a self-reported measure,
which is vulnerable to validity issues. The genetic variant
in the ABO gene is a single nucleotide polymorphism, rs505922
– a T nucleotide at this location is associated with a
lower risk. The P value here is measured at 0.88 – which
is not statistically significant.
23andMe state that
these preliminary findings support at least two recently published
pre-print studies, one by Zhao et al and another by Ellinghaus
et al that explore the role of the ABO gene in COVID-19.
LOOKING AT BLOOD
TYPES
Several studies
have also suggested that blood group could be implicated in
susceptibility and severity for COVID-19, and as such, the 23andMe
study is also exploring this.
The company estimated
the contribution to risk of blood group by comparing each blood
group against each of the others in the data from the 750,000
enrolled participants.
In the dataset available
from the survey, the percentage of respondents that reported
a positive test for COVID-19 was lower for individuals that
are O blood type (1.3%), compared to A (1.4%), B (1.5%) and
AB (1.5%) blood types. Individuals within groups A, B, and AB
were not statistically different from one another, and this
relationship stands when adjusting the measures for age, sex,
BMI, race, ethnicity and co-morbidities.
A CLOSER LOOK AT
BLOOD GROUP O
From 23andMe's reported
data set, there were no statistical differences between self-reported
rhesus factor (blood type + or -) in blood group O individuals,
challenging the findings of previous research.
To assess blood
group with regards to risk of acquiring infection, the company
restricted the data to individuals with a high probability of
exposure, such as health care professionals, essential workers
and individuals with close contact with known cases. The trend
in results reflected the original dataset, with the reporting
of a positive COVID-19 test being 3.2% for blood group O, 3.9%
for A, 4.0% for B and 4.1% for AB.
Blood type O showed
a protective effect against both acquiring (OR = 0.86, p <
0.0001), and being hospitalized for the infection (OR = 0.81,
p = 0.05). The protective effect of acquiring the infection
strengthened in models restricted to the “exposed”
population (OR = 0.81, p < 0.0001).
In percentages,
in the entire population, individuals with blood group O were
9-18% less likely to test positive when compared to other groups.
"Exposed" individuals with blood group O were 13-26%
less likely to test positive.
The research study
is still ongoing, and enrolment can be completed online. In
a press release the company says: "Ultimately, we hope
to publish our research findings in order to provide more insight
into COVID-19 for the scientific community."
