|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Tada, H, Shiffman, D, J Smith, G, Sjögren, M, Lubitz, SA, Ellinor, PT, Louie, JZ, Catanese, JJ, Engström, G, Devlin, JJ, Kathiresan, S, Melander, O|
|Date Published||2014 Oct|
|Keywords||Aged, Atrial Fibrillation, Cohort Studies, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke|
BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is prevalent and there is a clinical need for biomarkers to identify individuals at higher risk for AF. Fixed throughout a life course and assayable early in life, genetic biomarkers may meet this need. Here, we investigate whether multiple single nucleotide polymorphisms together as an AF genetic risk score (AF-GRS) can improve prediction of one's risk for AF.
METHODS: In 27 471 participants of the Malmö Diet and Cancer Study, a prospective, community-based cohort, we used Cox models that adjusted for established AF risk factors to assess the association of AF-GRS with incident AF and ischemic stroke. Median follow-up was 14.4 years for incident AF and 14.5 years for ischemic stroke. The AF-GRS comprised 12 single nucleotide polymorphisms that had been previously shown to be associated with AF at genome-wide significance.
RESULTS: During follow-up, 2160 participants experienced a first AF event and 1495 had a first ischemic stroke event. Participants in the top AF-GRS quintile were at increased risk for incident AF (hazard ratio, 2.00; 95% confidence interval, 1.73-2.31; P=2.7×10(-21)) and ischemic stroke (hazard ratio, 1.23; 95% confidence interval, 1.04-1.46; 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
CONCLUSIONS: An AF-GRS can identify 20% of individuals who are at ≈2-fold increased risk for incident AF and at 23% increased risk for ischemic stroke. Targeting diagnostic or therapeutic interventions to this subset may prove clinically useful.
|PubMed Central ID||PMC4346099|
|Grant List||282255 / / European Research Council / International |
K23 HL114724 / HL / NHLBI NIH HHS / United States
1K23HL114724 / HL / NHLBI NIH HHS / United States