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Stroke DOI:10.1161/STROKEAHA.114.006072

Twelve-single nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke.

Publication TypeJournal Article
Year of Publication2014
AuthorsTada, 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 Published2014 Oct
KeywordsAged, 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.


Alternate JournalStroke
PubMed ID25123217
PubMed Central IDPMC4346099
Grant List282255 / / European Research Council / International
K23 HL114724 / HL / NHLBI NIH HHS / United States
1K23HL114724 / HL / NHLBI NIH HHS / United States