Twelve–Single Nucleotide Polymorphism Genetic Risk Score Identifies Individuals at Increased Risk for Future Atrial Fibrillation and Stroke

Study Questions:

Can a panel of single nucleotide polymorphisms (SNPs) improve prediction of atrial fibrillation (AF) and stroke?


A community-based cohort of 27,471 subjects was followed for approximately 14 years for incident AF and stroke. Models that adjusted for established AF risk factors were used to determine the association of a 12-SNP, AF-genetic risk score (GRS) with incident AF and stroke.


During follow-up, 2,160 participants experienced an AF event and 1,495 experienced stroke. Participants in the top AF-GRS quintile were at increased risk for AF (hazard ratio [HR], 2.00; p = 2.7 × 10 – 21) and stroke (HR, 1.23; p = 0.02) when compared with the bottom quintile. Addition of the AF-GRS to established AF risk factors modestly improved both discrimination and reclassification (p < 0.0001 for both).


The authors concluded that an AF-GRS can identify 20% of individuals who are at twofold increased risk for AF and at 23% increased risk for stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful.


Approximately 50% of AF risk is due to established risk factors such as hypertension, age, heart disease, obesity, and diabetes. There is also a significant heritable component to AF, as demonstrated by familial AF and genome-wide association studies that have identified at least 12 common SNPs associated with AF. Previous studies have shown increased risk for AF using similar SNP panels; thus, this AF-GRS appears to be reproducible across diverse populations. Whether early identification of increased AF risk will lead to preventive measures that reduce this risk will require further study.

Clinical Topics: Prevention, Hypertension

Keywords: Stroke, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Risk Factors, Obesity, Hypertension, Diabetes Mellitus

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