Novel population-based approach to examine families where AF occurs with left atrial fibrosis

Atrial fibrillation (AF) is a condition that produces an irregular heartbeat that affects about two percent of the general population and six percent of people over 65 years of age. AF increases the risk of heart failure and stroke. While researchers have long believed genetics play a role in AF, decades of searching have revealed few culpable genes.

Researchers at University of Utah Health developed a population-based approach to examine families where AF occurs with left atrial fibrosis, scar tissue that forms around the heart. They believe this tactic lays the foundation to identify genes that predispose a person to an increased risk for AF and fibrosis.

Traditional methods have been tried by gifted scientists and not yielded the results that we hoped for. We took a different approach to identify people with AF. We merged resources unique to the state to make real progress."

Brent Wilson, MD, PhD, director of the Cardiovascular Center and Cardiology Clinical services at U of U Health and first author on the paper

Wilson collaborated with Lisa Cannon-Albright, PhD, Chief of Genetic Epidemiology and reknown expert in population genetics, Frank Sachse, Senior Scientist at the Cardiovascular Research and Training Institute, and Nassir Marrouche, Executive Director of the Comprehensive Arrhythmia Research and Management (CARMA) Center at U of U Health, who developed a database of more than 2,000 patients diagnosed with atrial fibrillation using late gadolinium enhanced magnetic resonance imaging (LGE-MRI).

According to Marrouche, this form of MRI is very powerful.

"Now we can define high-risk groups early and follow them using LGE MRI to hopefully detect or even prevent atrial fibrillation and its consequences of stroke, heart failure, and mortality," said Marrouche, a contributing author on the study.

The group applied AF patient MRI data to the Utah Population database (UPDB), a collection of genealogical data that extends to the mid-1800s and includes more than three million individuals who represent 3 to 16 generations.

"This database is huge; [it] essentially [includes] everyone in Utah going back to the original pioneers [and is paired with] medical records to look for people with AF and left atrial fibrosis," Wilson said.

By pairing these unique sources, the research team explored familial relationships among all individuals in the study. They identified 157 high-risk pedigrees in the Utah population that include 2 to 12 patients with AF and fibrosis. Thirty-seven of these pedigrees include four or more familial cases of atrial fibrillation and fibrosis.

Wilson notes that not every person with atrial fibrillation and left atrial fibrosis have genealogy data available in the UPDB. In addition, women have lower linkages in the database due to name changes. The UPDB is also predominantly a reflection of the genetics of people of Northern European origin.

The Utah group hopes to use these results to begin gene sequencing in high-risk families to identify a gene variant that could cause fibrosis or atrial fibrillation. These findings could help people across the country and the entire world.

"The results of this unique study design show atrial fibrillation with fibrosis is a specific subset of the disease that has a strong genetic contribution," said Cannon-Albright. "It is exciting for us to see Utah resources providing new understanding to the genetics of many different diseases."

Source:
Journal reference:

Wilson, B.D. et al. (2019) Evidence for a Heritable Contribution to Atrial Fibrillation Associated with Fibrosis. JACC Clinical Electrophysiology. doi.org/10.1016/j.jacep.2019.01.002.

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