Can AF be inherited? Understanding the Genie in the bottle
Channel: York Cardiology
Date: 18/11/2020

Introduction
AF is commonly seen in older patients with multiple comorbidities such as diabetes, high blood pressure, obesity, vascular disease and sleep apnoea. When those patients ask me why they developed AF, i tend to blame it on age, lifestyle and inflammation and say to them that maybe AF is a symptom of these underlying problems.
However there is another group of patients that I see with AF. These are young patients who don’t have many comorbidities at all and who are fit and live good lifestyles. They are often even more likely to ask me why they developed AF and when they do, i am usually at a complete loss to explain the reason why. 
Similarly whilst we appreciate that alcohol can lead to AF because of its toxic effects on the heart, what we can’t explain is the scenario where a bunch of young people go and have a drinking binge and whilst they may all drink similar amounts only one of them goes into AF then  next day - surely it cant just be about the alcohol - there must be something different about that individual. So in these settings the only explanation i can give patients is perhaps they had a genetic vulnerability.
As our understanding of AF has improved, we are beginning to realise that AF can be inherited and in this video, I want to go through what we know about genetic or familial AF.
Recent studies have suggested that upto 30% of patients with AF and without an indentifiable cause have a history of AF in the family. 
We also are beginning to realise that there may be changes in some genes that can cause AF on their own but there may be changes in other genes that just increase the risk of AF but the AF actually only comes out when there are additional lifestyle or environmental factors that are added in. In a simplistic way, some people inherit the genie and some inherit a genie in a bottle. Something in the environment or lifestyle then breaks the bottle and the genie escapes. Once the genie escapes, he does get back into the bottle but as the bottle is cracked, he is far more likely to escape again. 
Many patients will say to me that they are not aware of AF in any family history of AF. In those patients it is possible that family members may still have had the genie in the bottle and the bottle was never broken or may be that they may have had AF but never knew because AF can be silent. 
It is believed that AF can be caused by mutations in single genes or what is termed as polymorphisms in multiple genes. 
In terms of single genes the first that was found to be associated with AF is called KCN01 which is responsible for  making an electrical potassium-regulating  ion channel in the outer membranes of our heart muscle cells. Mutations in ion channels may increase or decrease the flow of ions across the cell membranes and therefore alter the way the heart beats. Geneticists have also found mutations in sodium channels and certain genes which regulate transcription factors. 
As mentioned earlier you can have polymorphisms in multiple genes (upto 2 dozen genes) and each polymorphism/variation may just slightly increase the person’s chance of AF but if you have a bunch of polymorphisms together then the risk could be much higher - especially if these are then combined with toxins, chronic disease affecting the heart, chronic inflammation or even things like excessive stress and dehydration.
How is it inherited?
We are still learning but in those patients who have a single mutation likel the KCN01, it is believed that the inheritance is autosomal dominant. This means that one copy of the altered gene in each cell is enough to cause the disorder. So basically if you have the mutation then there is a 50% chance of passing it on to your child. 
How does the bottle break?
There are certain triggers which help break the bottle. The more of the triggers that happen at the same time the more likely that the bottle will break and the genie will come out.

Here are some of the triggers that contribute:
Emotion - stress, anxiety
Dehydration
Physical exhaustion
Lack of sleep
Alcohol especially wine
Stimulants (excessive caffeine)
Hormonal changes
A bloated stomach
Intercurrent illness