Researchers at the Broad Institute in the USA searched for links between genetic variants and irregular heartbeat in young and middle-aged adults.
Atrial fibrillation is a type of irregular heartbeat. This irregular heartbeat is caused by electrical signals in the heart that are too fast, causing less efficient pumping of the blood. If left untreated, atrial fibrillation can lead to problems such as stroke or heart failure.
The risk of atrial fibrillation increases with age as well as high blood pressure, diabetes, and other heart conditions. However, this irregular heartbeat can also occur in young and middle-aged people. These cases are referred to as early-onset atrial fibrillation. Early-onset atrial fibrillation is rare, leading many experts to believe that it may be caused by genetic factors.
Genetics and disease
Everyone has differences in their DNA, some of which contribute to variation among people in traits like physical appearance and how our body functions. Differences among people in a DNA sequence are called genetic variants. There are many genetic variants throughout the human genome. While most genetic variants are harmless, some variants put people at a higher risk for developing certain diseases.
Over the past couple of decades, many medical research studies have focused on genetic variants that may contribute to disease. One commonly used method to find genes associated with disease is genome-wide association studies (GWAS).GWASs examine many different genetic variants in people with a disease and people without the disease. Researchers then determine what variants are present in people with the disease much more often than in people who do not have the disease.
Researchers from the Broad Institute at MIT and Harvard in the USA led a study using GWAS to search for genetic variants that may contribute to early-onset atrial fibrillation. This study was published in JAMA. They performed the GWAS using 2,781 Americans under the age of 66 who previously participated in 9 studies under the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine Consortium.
A link between irregular heartbeat, heart failure, and a genetic variant
The researchers found a link between an irregular heartbeat and a mutation in the gene TTN. TTN codes for the protein titin, which is important for maintaining the structure and strength of heart muscle tissue. Defects in titin have also previously been linked to heart failure.
The TTN mutation was only present in 2.1% of study participants with early-onset atrial fibrillation. However, the mutation was present in >6% of participants with early-onset atrial fibrillation under 30 years old. This suggests a role for defects in TTN in the development of atrial fibrillation in young people. In addition, participants with the TTN mutation were on average diagnosed with early-onset atrial fibrillation five years younger than those without the TTN mutation.
Results of this study suggest a possible role for TTN loss in an irregular heartbeat in young people. Given these results, young patients with an irregular heartbeat may be tested for TTN mutations in the future to determine whether they should be screened for other heart problems or given specialized treatments.
Current treatment for patients with the irregular heartbeat targets electrical signalling problems. However, early-onset atrial fibrillation in patients with TTN mutations may be caused, at least in part, by problems with the structure of the heart muscle. Further studies into how TTN mutations contribute to irregular heartbeat are needed to determine whether patients with TTN mutations should receive different treatments.
One limitation of this study is that all participants were of European descent. Further studies will need to be conducted to determine whether there is a link between TTN mutations and early-onset atrial fibrillation in other ethnic groups as well. In addition, because this study focused on atrial fibrillation in young and middle-aged people, it is unclear whether mutations in TTN may also contribute to the irregular heartbeat in older adults.
Written by Melissa H. Wong, MSc
Reference: Choi SH, Weng L-C, Roselli C, et al. Association between titin loss-of-function variants and early-onset atrial fibrillation. 2018. JAMA 320(22):2354-2364.