Researchers find link between atrial fibrillation and mutations in a gene associated with heart disease

Researchers have discovered a new link between atrial fibrillation (Afib)—a potentially life-threatening condition that causes rapid, irregular heartbeat—and mutations in a gene associated with heart disease.

To investigate genetic influences behind early-onset Afib, a nationwide research team collected whole genome sequence data from 2,781 Americans under the age of 66 who took part in nine studies that participated in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) Consortium. The researchers found a strong relationship between early-onset Afib and mutations that break TTN, a gene that helps maintain the structure of heart muscle. TTN encodes a protein called titin, which acts like a molecular scaffold within heart muscle cells. Defects in titin are linked to many forms of cardiomyopathy, or diseases of the heart muscle. However, while cardiomyopathy patients often experience Afib as well, the molecular relationship between the two is still unclear, according to the researchers.

The study represents the first time that researchers have been able to link so-called loss-of-function mutations in a single gene to early-onset Afib, they said. The study, which is partly funded by NHLBI, appeared in JAMA.

“This study is a key paper for broadening our understanding of the genetic underpinnings of atrial fibrillation and underscores the value TOPMed provides the scientific community because of its genetic data, study design, and multi-ethnic representation,” said George Papanicolaou, Ph.D., a project officer for the study and a research geneticist with NHLBI. “The results from this study may one day point to tailored treatments for early-onset Afib but will need further investigation.”