The Role of Genomics in Atrial Fibrillation

Patrick Ellinor, MD, is the director of the Telemachus & Irene Demoulas Family Foundation Center for Cardiac Arrhythmias at Massachusetts General Hospital. He and his team leverage genome-wide association studies to identify over 100 different genetic determinants of atrial fibrillation.

Subscribe to the latest updates from Cardiovascular Advances in Motion

Thank you for subscribing!

Error: Please enter a valid email address.

Email Address Submit

Transcript

It’s important to understand that genetics and genomics are really going to have two roles in the next five years.

The first is that with some very large what are called genome-wide association studies, or population-based studies, where we take an entire population of AFib on one side, and people without AFib on the other, and compare them at a genetic level, we've identified over 100 different genetic determinants of atrial fibrillation. What we will do with this information are a few things. First, we will look to say do these genetic variants actually help us to stratify the risk of getting the disease? The second is that it will tell us about what are the molecular mechanisms or the steps that lead to the initiation and maintenance of this arrhythmia. And then the third is to say can we use these new genes as potential therapeutic targets to develop new treatments for this common arrhythmia.

We have also taken a second approach, which is to look very carefully at younger healthier people with AFib and we've sequenced their entire genome--so the three billion building blocks that we’re each made up of--and what we found is, particularly among young healthy people with atrial fibrillation, a striking minority of them had a deletion or loss of function of one of the major proteins in the heart. So what that opens up is really two avenues. With these hundred genes one can imagine using that genetic information to say what are the molecular pathways for atrial fibrillation, and then second, can we use those genes as targets to develop new drugs to treat AFib?

On the other hand, when you look at the mutations that we find in young healthy people it opens up the idea that in those younger individuals, instead of just thinking about blood thinners or ablations, we would actually be carefully screening both those individuals and their families for carriers of these different genetic variants.

Well, I think what is tremendously exciting in our field of the genetics of our cardiovascular disease is the sheer scale at which the studies are being done. We went from 15 years ago working on a few hundred people to now working on over 100,000 individuals in a lot of our genetic studies. That has allowed us to identify numerous genetic variants that are associated with these diseases, and intriguingly, we are able to take these genetic variants and hopefully use those to develop new drugs to treat AFib and other common conditions in the years to come.