The genetics of irregular heart rhythm and what genetic testing is available

The genetics of irregular heart rhythm and what genetic testing is available
Atrial fibrillation is an under-diagnosed heart condition that causes irregular heartbeats. If left undiagnosed or untreated, it can predispose a person to blood clots and is a leading cause of stroke. We’ve scoured the literature to give you an overview of the latest science on the genetic underpinnings of atrial fibrillation. 
Written by Christina Ren, Certified Genetic Counselor 
Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. “Genetics for Humans” is where we unpack how genetics impacts our everyday lives and the latest tools to help you build a healthier family.

What is atrial fibrillation and how does it impact individuals? 

Every heartbeat is controlled by the heart’s electrical system. Atrial fibrillation happens when the electrical signal becomes irregular. This can be dangerous because the body is not able to efficiently and consistently pump blood to the rest of the body, increasing the chance of blood clots. People with atrial fibrillation are 5 times more likely to have a stroke. 

While most of us have experienced the feeling of our heart racing or an occasional skipped heartbeat, people with atrial fibrillation often experience symptoms for extended periods of time. It can be a scary experience; some describe that their heart “flip-flops, bangs against their chest wall” and that they felt like they were “gasping for air.” Others may have no symptoms, but still have an increased risk for life-threatening heart complications. 

How common is atrial fibrillation? 

An estimated 33 million people currently have atrial fibrillation (AF) worldwide, affecting 1 in 3 individuals over the course of their lifetime. Men tend to have an increased risk to develop atrial fibrillation compared with women. However, of the women that do have AF, they tend to have a higher risk for adverse outcomes like morality and stroke.   

Does atrial fibrillation run in families? 

It definitely can, especially for those with a family history of early-onset atrial fibrillation (before age 45). 

A study of identical twins has estimated the heritability of atrial fibrillation to be 62%, indicating a strong genetic component. Having a parent with a history of AF increases a person’s risk over a 4-year study period by two-fold. 

Historically, clinical genetics has focused on specific arrhythmia genetic disorders such as Long QT syndrome and Brugada syndrome. Indications that would increase suspicion of a rare genetic disease and warrant further evaluation in a cardiovascular genetics clinic include: 

  • Unexplained sudden death or cardiac arrest 
  • Seizures
  • Fainting spells
  • Exercise intolerance 
  • Very early-onset cardiac events

However, the vast majority of the time, people with atrial fibrillation do not have these rare genetic disorders that impact 1 in every few thousand individuals. We distinguish between “inherited” and “common” types of atrial fibrillation because genetics can still impact the chance of developing common AF, even if inherently less obvious. 

Is there a single genetic cause for atrial fibrillation?

Most of the time, no. There is no single “Irregular Heart Rhythm Gene” like the Huntington’s disease gene that explains it all.  

Here, we again need to distinguish rare inherited forms of arrhythmia and common, “garden variety” atrial fibrillation. 

Single genes such as KCNQ1 have been identified to cause inherited forms of AF. These genes are often involved in ion channel function. For individuals families with inherited forms of AF, single gene panel testing can be very helpful for at-risk relatives. However, the single gene mutations are rare and have a small impact on common atrial fibrillation. 

This means the vast majority of people that have atrial fibrillation don’t have a single gene mutation. So, if you just did genetic testing looking for single gene cardiac genes, most of the time, you wouldn’t find anything meaningful to you.

Given that inherited forms of atrial fibrillation only explains a very small portion of AF cases, what about most cases of AF? After decades of research, what’s become increasingly apparent is that most of the time, there is no single genetic cause of atrial fibrillation. The reality is more complex. To properly measure genetic predisposition to atrial fibrillation, you have to assess the whole landscape by looking at many genes and genetic markers combined.  

Is there a genetic test for the common form of atrial fibrillation?

Yes, there is now a way to measure your genetic predisposition to common atrial fibrillation. This is different from a diagnosis, however. Genetic screening can tell you if you are more or less likely to develop atrial fibrillation than the average person based on your genetic background, independent of other clinical risk factors like diabetes or high blood pressure.  

This is done by comparing the genetic makeup of tens of thousands of individuals diagnosed with atrial fibrillation (“cases”) with individuals without AF (“controls”). A recent study with data from over 400,000 individuals suggests that based on genetics, 6% of the general population have over a 3-fold increased risk for atrial fibrillation. 

With advanced genetic testing like what we do here at Orchid, you can get a sense of your genetic predisposition to atrial fibrillation and remove some of the guesswork on what you can pass on to your future children. 

What actions can I take based on the information from a genetic test for atrial fibrillation? 

If you or your future child has an elevated genetic risk for atrial fibrillation, the risk of developing atrial fibrillation at some point in life can be up to 3 times higher than in the general population. 

The useful thing about your results is that if you identify certain genetic vulnerabilities that can impact you or your future children, you can potentially do something about it and mitigate these risks. Ways you can act on your results include:

  • Offset genetic risks with healthy lifestyle choices. Genetics is just one component of your chances of getting atrial fibrillation. This means you can significantly lower your overall risk with personal lifestyle choices, which is especially important if you have a higher genetic risk. AF is associated with risk factors like obesity, hypertension, diabetes, sleep apnea, and physical inactivity. The hopeful picture is that about 40% of cases of atrial fibrillation can be potentially managed without surgery or medications by eliminating these modifiable risk factors. Healthy lifestyle also significantly lowers risk for stroke and heart failure.  
  • Consider screening for atrial fibrillation using wearable technology. Wearables like the Apple watch can now check for atrial fibrillation and notify users when irregular heart rhythm is detected. This may be especially useful for people with an elevated genetic predisposition to atrial fibrillation for early detection and potential stroke prevention through recommended medications. 
  • Embryo screening to reduce your child’s potential genetic risks. Embryo screening allows you to quantify each embryo’s genetic risk for atrial fibrillation and other common conditions. This allows you to prioritize the transfer of embryos with the lowest genetic risk and thus reduce your future child’s genetic risks.  

Key takeaways 

  • Atrial fibrillation is a common condition that can lead to life-threatening heart complications if undiagnosed or untreated. 
  • Past family studies have shown that genetics play an important role in the chance of developing atrial fibrillation. 
  • Advanced genetic testing can now see if this genetic component to atrial fibrillation can be quantified for you and your family. 
Resources 

Orchid offers advanced genetic testing for couples planning on building their family. We use advanced tools and smart, caring humans to help you give your future children the best shot of a healthy life. Conceive with greater confidence and peace of mind

12/29/2020
Genetics
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