What you carry at this position in your DNA and what research says about it.
Atrial Fibrillation Risk: 6/10 evidence, 39 publications.
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Sample genotype (not yours): C/C
Typical Heart Rhythm and Stroke Risk
The presence of two copies of the common C allele is associated with a typical heart rhythm and a lower risk of atrial fibrillation. This genotype avoids the elevated risk of stroke and irregular heartbeats linked to the variant.
What this genotype means: Typical heart rhythm; Lower risk of atrial fibrillation; Baseline stroke risk.
Sample genotype (not yours): C/T
Increased Risk of Atrial Fibrillation
One copy of the T allele is associated with a moderately increased risk of atrial fibrillation and ischemic stroke. This genetic variation can influence the electrical stability of the heart's upper chambers.
What this genotype means: ~1.4x higher atrial fibrillation risk; Elevated risk of ischemic stroke; Altered PITX2 gene regulation.
Sample genotype (not yours): T/T
Elevated Risk of Atrial Fibrillation and Stroke
The presence of two copies of the T allele is associated with a significantly higher risk of atrial fibrillation and a prolonged heart conduction interval. This genotype is also linked to an increased risk of cardioembolic stroke.
What this genotype means: ~1.5x to 1.7x higher atrial fibrillation risk; Prolonged PR conduction interval; Elevated risk of cardioembolic stroke.
Gene function and biological role
Gene Function: PITX2 is a crucial transcription factor located on chromosome 4q25. It plays a fundamental role during embryonic development, particularly in establishing left-right asymmetry and guiding the formation of the left atrium and pulmonary vein myocardium [1]. In adulthood, PITX2 remains active in the heart, helping to regulate electrical conduction, resting membrane potential, and calcium balance within atrial cells [2]. Decreased expression or dysfunction of PITX2 can lead to structural remodeling, such as left atrial dilatation, and create an unstable electrical environment in the heart [3]. This makes the heart highly susceptible to rapid, irregular rhythms [3].
Variant Impact: The rs2200733 variant is an intergenic single nucleotide polymorphism located on chromosome 4q25, positioned near the promoter region of the PITX2 gene [1]. Although it does not alter the protein sequence of PITX2 directly, it acts as a regulatory modifier that influences PITX2 transcription and expression levels [1]. The presence of the T allele at this locus is strongly associated with an increased risk of developing atrial fibrillation [1]. This genetic change is also linked to a higher susceptibility to cardioembolic and ischemic strokes [3]. Additionally, carriers of the T allele tend to have a prolonged PR interval, indicating altered electrical conduction through the heart's atria [2].
Key Insight: This genetic variant is located in a non-coding region but acts as a powerful remote control, altering the expression of a nearby gene crucial for heart development and rhythm.
Location: PITX2. Chromosome 4 · 4q25 · 110.8 Mb
Estimated prevalence by population
Global 67.1%; European 75.2%; African 60.9%; East Asian 24.7%; South Asian 75.8%; Americas 59.4%; Ashkenazi 48.4%; Finnish 71.8%; Middle Eastern 61.2%; Amish 97.2%.
Estimated CC genotype frequency.
Global 28.9%; European 23.1%; African 34.3%; East Asian 50.0%; South Asian 22.5%; Americas 35.3%; Ashkenazi 42.3%; Finnish 25.9%; Middle Eastern 34.1%; Amish 2.8%.
Estimated CT genotype frequency.
Global 4.0%; European 1.8%; African 4.8%; East Asian 25.3%; South Asian 1.7%; Americas 5.2%; Ashkenazi 9.3%; Finnish 2.3%; Middle Eastern 4.7%; Amish < 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Heart Rhythm & Conduction
Atrial Fibrillation. Evidence: 6/10. Source: PMID 17603472. ~14% Lower Risk.
Cardiac Conduction. Evidence: 3/10. Source: PMID 24161141. Typical Conduction.
Stroke
Ischemic Stroke. Evidence: 8/10. Source: PMID 18991354. Typical Risk.
Cardioembolic Stroke. Evidence: 6/10. Source: PMID 26708676. Typical Risk.
Showing effects for C/T genotype
Atrial Fibrillation. Evidence: 6/10. Source: PMID 17603472. ~1.4x Higher Risk.
Ischemic Stroke. Evidence: 8/10. Source: PMID 18991354. Increased Risk.
Cardioembolic Stroke. Evidence: 6/10. Source: PMID 26708676. Increased Risk.
Showing effects for T/T genotype
Atrial Fibrillation. Evidence: 6/10. Source: PMID 17603472. ~1.5x to 1.7x Risk.
Cardiac Conduction. Evidence: 3/10. Source: PMID 24161141. Prolonged Interval.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Two copies of the standard protective allele at this chromosome 4q25 locus are present. Large-scale genome-wide association studies have consistently shown that this genetic profile is associated with a lower risk of developing atrial fibrillation compared to carriers of the T allele [1]. Normal electrical conduction through the heart's upper chambers is typically maintained, as reflected by a standard PR interval [2]. Consequently, the risk of experiencing a cardioembolic or ischemic stroke remains at baseline levels [3]. Maintaining a heart-healthy lifestyle, including regular exercise and blood pressure management, further supports cardiovascular wellness.
Typical heart rhythm; Lower risk of atrial fibrillation; Baseline stroke risk.
Sample genotype: CT (Heterozygous)
Possessing one copy of the T allele at rs2200733 is linked to a roughly 1.4-fold increase in the risk of developing atrial fibrillation [1]. This irregular heart rhythm can lead to blood pooling in the atria, which elevates the risk of blood clots and subsequent ischemic stroke [2]. Clinical studies indicate that this variant alters the regulatory expression of the nearby PITX2 gene, which is essential for maintaining normal cardiac electrical pathways [1]. While this genotype slightly increases susceptibility, many individuals with this variant never develop heart rhythm issues. Managing modifiable risk factors such as high blood pressure, sleep apnea, and alcohol consumption is highly beneficial for maintaining cardiovascular health [3].
~1.4x higher atrial fibrillation risk; Elevated risk of ischemic stroke; Altered PITX2 gene regulation.
Sample genotype: TT (Homozygous)
Two copies of the T allele are associated with a 1.5-fold to 1.7-fold increased risk of developing atrial fibrillation, the most common type of irregular heartbeat [1]. This genetic variant is also linked to a significantly prolonged PR interval, which reflects slower electrical conduction through the atria [2]. Because atrial fibrillation can cause blood clots to form in the heart, this genotype also carries an elevated risk of cardioembolic stroke [3]. The underlying mechanism involves altered expression of the PITX2 gene, which plays a critical role in the development and electrical function of the left atrium [1]. Proactive cardiovascular care, including monitoring for irregular heartbeats and managing blood pressure, is particularly important for individuals with this genotype.
~1.5x to 1.7x higher atrial fibrillation risk; Prolonged PR conduction interval; Elevated risk of cardioembolic stroke.
Variants with shared genetic architecture
rs6843082 · PITX2 Gene · Chr 4 · Atrial Fibrillation Risk
rs6882076 · TIMD4 Gene · Chr 5 · Cardiovascular Risk
rs133885 · MYO18B Gene · Chr 22 · Atrial Fibrillation Risk
Variants conferring risk of atrial fibrillation on chromosome 4q25.
Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke.
Relation of Obstructive Sleep Apnea and a Common Variant at Chromosome 4q25 to Atrial Fibrillation.
Content updated August 2026.
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