Arrhythmia and Atrial Fibrillation: The Role of Genetics

Heart rhythm disorders can have different causes, and stress is only one of the possible triggers. Atrial fibrillation, one of the most common types of arrhythmia, has a well-studied genetic component. A meta-analysis of more than 180,000 cases identified more than 350 genetic loci associated with this rhythm disorder (Roselli et al., Nat Genet, 2025). Genetic factors can shape individual predisposition, but the presence of a heart rhythm disorder is confirmed by an ECG or long-term electrocardiographic monitoring.

What Arrhythmia Is and How It Differs From a Fast Heartbeat

An increased heart rate does not necessarily indicate a rhythm disorder: during physical activity, stress, or after caffeine intake, it can rise physiologically. Arrhythmia, by contrast, is a disturbance in the formation or conduction of electrical impulses in the heart that can change the rate, regularity, or sequence of its contractions (Ludhwani & Wieters, StatPearls, 2023).

Subjective sensations do not always make it possible to tell these conditions apart. Both a physiological increase in heart rate and a rhythm disorder can feel like a fast, strong, or irregular heartbeat. The difference between them is determined by the nature of the heart's electrical activity — in particular, by whether the formation or conduction of electrical impulses is disturbed.

For more on how cardiovascular risk develops, see the article The Cause of Cardiovascular Disease Is Not Only “Bad” Cholesterol: What Genetics Says About It.

What Arrhythmia Risk Depends On

Heart rhythm can be affected simultaneously by acute triggers that can provoke an episode of arrhythmia and by factors that gradually change the electrical and structural properties of the heart (Ludhwani & Wieters, StatPearls, 2023). The latter include age, arterial hypertension, diabetes, obesity, sleep apnea, and chronic kidney disease. Non-cardiac causes include thyroid dysfunction and electrolyte disorders (Ludhwani & Wieters, StatPearls, 2023). In a cohort study of nearly 15,000 people with a median follow-up of 19.7 years, the lowest serum potassium and magnesium levels were associated with an increased risk of atrial fibrillation, although Mendelian randomization did not confirm a causal relationship (Wu et al., BMC Genomics, 2024).

Arrhythmia risk is shaped by a combination of factors: age, the state of the cardiovascular system, comorbidities, and lifestyle. Within this combination, stress acts as a trigger for individual episodes, while predisposition is determined by a longer list of factors.

What Atrial Fibrillation Is and How It Differs From Other Arrhythmias

Arrhythmias include conditions that differ in their mechanism, manifestations, and clinical significance. Atrial fibrillation (AFib) is a specific type of arrhythmia in which rapid, uncoordinated electrical activity arises in the atria, and they lose the ability to contract effectively. An important feature of atrial fibrillation, one of the most common types of arrhythmia, is that it can run its course without noticeable symptoms for a long time, so it is sometimes diagnosed only during an examination or once complications have already developed (Ludhwani & Wieters, StatPearls, 2023).

Consequences of Atrial Fibrillation for Heart Function

In atrial fibrillation, the atria lose the ability to contract mechanically in an effective way, so they do not actively pump blood into the ventricles, which fill mostly passively (Ludhwani & Wieters, StatPearls, 2023).

Uncoordinated impulses from the atria reach the ventricles irregularly, since the ventricular response depends on the conduction properties of the atrioventricular node. As a result, the intervals between ventricular contractions become uneven, and the heart rate usually rises to 120–160 beats per minute and in some cases can reach 200 (Ludhwani & Wieters, StatPearls, 2023). Such an irregular rhythm of contractions may be felt as skipped beats or palpitations.

Impaired mechanical function of the atria has another consequence: the atrial appendage does not empty completely, and blood stasis in it creates conditions for thrombus formation and increases the risk of thromboembolic complications, including stroke. If a high heart rate persists for a long time, there is a risk of developing heart failure and tachycardia-induced cardiomyopathy (Ludhwani & Wieters, StatPearls, 2023). Therefore, the clinical significance of atrial fibrillation is not limited to the sensation of an irregular heartbeat itself.

The Genetic Component of Atrial Fibrillation

The risk of atrial fibrillation is multifactorial and is determined by the combined effect of many genetic variants, each with a small individual effect. Genome-wide association studies (GWAS) have consistently identified a growing number of genomic regions associated with atrial fibrillation risk. A 2018 study, in which the primary analysis was performed in a Norwegian cohort with subsequent replication in an independent sample, identified seven loci associated with atrial fibrillation risk, as well as a link between some of the signals and cardiac development and cardiac conduction (Nielsen et al., Am J Hum Genet, 2018).

The largest meta-analysis, which combined data from more than 180,000 atrial fibrillation cases and nearly 1.5 million people without the condition, identified more than 350 genetic loci associated with atrial fibrillation. This is roughly twice as many as were previously known (Roselli et al., Nat Genet, 2025). At 139 of these loci, the authors identified genes related to the heart muscle's ability to contract, its prenatal development, and signaling between heart cells. A separate study that combined genome and exome sequencing data from more than 50,000 people with atrial fibrillation found associations with rare coding and structural variants that are harder to detect with standard GWAS approaches (Choi et al., Nat Genet, 2025).

Genetic Risk Assessment for Atrial Fibrillation

The hundreds of identified loci do not produce a practical result on their own: the effect of each variant is too small to be assessed individually. For this purpose, a polygenic risk score (PRS) is used, which sums up the contribution of thousands of variants into a single numerical measure of genetic predisposition. If this measure is expressed in percentiles, it reflects where the result stands relative to a reference population, not the probability of developing atrial fibrillation.

A PRS built on data from the meta-analysis of more than 180,000 cases improved risk prediction compared with the clinical CHARGE-AF score (Roselli et al., Nat Genet, 2025). 

For more on how this measure is calculated, see the article What PRS Is and What the Numbers in Your Report Mean.

Unlike dynamic laboratory measures, a genetic assessment does not need to be repeated: a person's genotype remains unchanged throughout life, so the calculated predisposition does not depend on age. Only the interpretation can change: if the scientific model or calculation method is updated, the assessment is revised based on the same data.

Genetic Predisposition and Diagnosis of Atrial Fibrillation

A genetic result describes an inherited predisposition to atrial fibrillation and does not reflect the current state of the heart rhythm. An ECG, by contrast, records the heart's electrical activity during the test and makes it possible to detect atrial fibrillation (if it is present during the recording).

Atrial fibrillation is diagnosed only when there is an ECG recording that documents it (ESC/EACTS, 2024 Guidelines for the Management of Atrial Fibrillation, 2024). Such documented atrial fibrillation is considered clinical regardless of whether symptoms are present. If an episodic form is suspected, a single recording may be insufficient, so longer rhythm monitoring may be needed to detect the arrhythmia.

When a Change in Heart Rhythm Requires Seeing a Doctor

A faster or irregular heart rhythm can occur as a physiological response to exertion, stress, or caffeine intake. It is worth seeing a doctor if such episodes recur, last a long time, occur without an obvious cause, or are accompanied by symptoms typical of rhythm disorders (Ludhwani & Wieters, StatPearls, 2023):

• dizziness,
• fainting,
• shortness of breath,
• chest discomfort,
• marked weakness.

The presence of these symptoms does not in itself indicate arrhythmia. At the same time, their absence does not rule out a rhythm disorder: some episodes of atrial fibrillation occur without noticeable manifestations (Ludhwani & Wieters, StatPearls, 2023).

Limits of Genetic Risk Assessment for Atrial Fibrillation

A genetic assessment adds to the picture of atrial fibrillation risk but does not determine its clinical course. The presence of arrhythmia, the frequency and duration of episodes, and their temporal pattern are established through clinical assessment, ECG, and, if necessary, long-term rhythm monitoring.

Clinical guidelines classify atrial fibrillation by its temporal pattern (first diagnosed, paroxysmal, persistent, and permanent) and take this characteristic into account when choosing a management strategy (ESC/EACTS, 2024 Guidelines for the Management of Atrial Fibrillation, 2024). That is why a genetic result should be considered in the context of clinical data and ongoing monitoring of heart health.

Apixmed Prism assesses genetic predisposition to atrial fibrillation and other heart rhythm disorders as part of the metrics related to the heart's electrical conduction. The result complements clinical information about cardiovascular risk and can be used as long-term genetic context when assessing heart health. 

Genetic predisposition to arrhythmia and atrial fibrillation can be assessed as part of a cardiovascular health test or within a full genetic profile covering more than 1,000 metrics.

Genetic test results are not a diagnosis and do not replace a consultation with a doctor. The Apixmed Prism report provides genetic context that complements examination results and helps you make decisions together with your doctor.

Sources

1. Roselli, C., Surakka, I., Olesen, M. S. et al. (2025). Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases. Nature Genetics, 57(3), 539–547. https://doi.org/10.1038/s41588-024-02072-3 

2. Choi, S. H. et al. (2025). Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk. Nature Genetics, 57, 548–562. https://doi.org/10.1038/s41588-025-02074-9 

3. Nielsen, J. B., Fritsche, L. G., Zhou, W. et al. (2018). Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development. American Journal of Human Genetics, 102(1), 103–115. https://doi.org/10.1016/j.ajhg.2017.12.003 

4. Van Gelder, I. C., Rienstra, M., Bunting, K. V. et al. (2024). 2024 ESC Guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal, 45(36), 3314–3414. https://doi.org/10.1093/eurheartj/ehae176 

5. Ludhwani, D., Wieters, J. S. (2023). Paroxysmal Atrial Fibrillation. StatPearls. StatPearls Publishing. Updated June 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK535439/

6. Wu, Y., Kong, X.-J., Ji, Y.-Y. et al. (2024). Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study. BMC Genomics, 25, 280. https://doi.org/10.1186/s12864-024-10197-2