Arina Puzriakova: What is a polygenic disorder?

In this explainer episode, we’ve asked Arina Puzriakova,
Scientific Curator at Genomics England, to explain what a
polygenic disorder is.


You can also find a series of short videos explaining some of the
common terms you might encounter about genomics on
our YouTube channel.


If you’ve got any questions, or have any other topics you’d like
us to explain, feel free to contact us
on info@genomicsengland.co.uk.


You can download the transcript or read it below.


Florence: What is a polygenic disorder? I'm joined by Arina
Puzriakova, Scientific Curator for Genomics England to find out
more. So, Arina, first things first. How can our genes affect our
health?  


Arina: So, genes are short sections of DNA that contain
information that the cells in your body need in order to make
proteins. Each gene carries the instructions for making a
specific protein, and each protein performs a different task that
allows the body to develop and function properly, depending on
the genes that we inherit from our parents. Also determines our
unique physical features such as our eye colour, hair colour, and
height. 


When a gene contains a change that disrupts the gene's
instructions, also known as a gene variant, in some cases, this
can lead to the production of a defective protein or prevents a
protein from being made altogether. A missing protein or one that
is not working properly can have a knock-on effect on how the
body functions and this can result in health issues or the
development of a genetic disorder. 


Florence: So then how can a gene variant lead to a
disorder?  


Arina: So the genetics of each disorder are unique. In some
cases, a change in a single gene is enough to cause a genetic
disorder, and these are known as monogenic disorders. These
conditions often occur in childhood and tend to cause severe
illness. individually, they are more rare affecting a smaller
number of people in the population, and usually they run in
families as parents pass the damaging variance onto their
children. 


But these changes can also happen spontaneously without a known
cause. An example of a monogenic disorder, which some may be
familiar with, is cystic fibrosis. Cystic fibrosis affects one in
every 2,500 babies born in the UK, meaning that there's about
11,000 people living with cystic fibrosis. 


Florence: So, we've just talked through monogenic disorders. What
do we mean by polygenic disorder?  


Arina: So polygenic disorders are on the other end of the
spectrum for disorders. 


They are caused by the combined effects of multiple different
genes. Individually, each gene has a very small effect on causing
the disease, but many variations in different genes can act
together to have a great impact on individual's susceptibility to
that condition. Environmental and behavioural factors such as
your lifestyle and diet also often have an effect. 


Polygenic disorders are much more common, typically affecting
millions of people in the population, and they're usually
diagnosed in adulthood.  


Florence: Could you give me an example of a polygenic
disorder?  


Arina: A common example of a polygenic disorder is type two
diabetes. It affects almost 4 million people in the UK. 


So this means that we know there are many genetic variants that
could have made these individuals more susceptible to diabetes,
but there are also other factors such as age or being overweight
that could have increased their risk. 


Florence: Are there specific challenges when it comes to
diagnosing or treating polygenic disorders? 


Arina: So, if I start with monogenic disorders, these are much
easier to test for because we simply need to look for the
presence or the absence of a faulty gene in order to determine
whether someone is a carrier of a genetic disorder. On the other
hand, testing for a polygenic disorder is a lot more complex as
they are influenced by the combined effects of many genes. 


Meaning there is no single genetic test or treatment that will
work for all patients with the same condition. We need large and
diverse groups of patients to study in order to accurately
determine which genes are important and which ones are not. 


And this can be challenging to obtain. Also accurately measuring
and comparing lifetime environmental factors and exposures
further complicates the assessment. 


Another challenge with polygenic disorders is that even though
they can cluster in families, the inheritance is not as clear cut
or predictable as it is with monogenic disorders. Carrying a
specific combination of genetic variants that are already known
to be associated with polygenic disorder does not necessarily
mean that you will definitely develop that disorder. 


However, this information can be used to calculate something
known as a polygenic risk score, and this provides an estimate
for the risk of developing polygenic disease at some point in
life based on individual's unique genetic profile. 


Florence: And why can knowing apologetic risk score be
helpful? 


Arina: So, by being informed about the probability of developing
a particular polygenic disease, an individual can make behaviour
or lifestyles changes that could help reduce their risk. To go
back to the previous example, somebody who is more likely to
develop type two diabetes based on their genetic makeup can do
things like maintain a healthy weight. And eat a healthy diet to
help reduce their risk of developing type two diabetes in the
future. 


Florence: That was Arina Puzriakova explaining what we
mean by polygenic disorder. If you'd like to hear more explainer
episodes like this, you can find them on our website at
www.genomicsengland.co.uk. Thank you for listening.