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Research Letter
May 14, 2012

Genetic Polymorphisms for Estimating Risk of Atrial Fibrillation in the General Population: A Prospective Study

Author Affiliations

Author Affiliations: Department of Cardiology, Lund University, Lund, Sweden (Drs Smith and Platonov); Department of Clinical Sciences, Lund University, Malmö, Sweden (Drs Smith and Melander and Mr Almgren); Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge (Drs Smith and Newton-Cheh); and Center for Human Genetic Research and Cardiovascular Research Center, Harvard Medical School and Massachusetts General Hospital, Boston (Dr Newton-Cheh).

Arch Intern Med. 2012;172(9):742-744. doi:10.1001/archinternmed.2012.786

Atrial fibrillation (AF) is a common cardiac disease and major risk factor for stroke, heart failure, and death. Tools for prediction of AF have been developed to identify individuals who might benefit from preventive therapies, incorporating conventional cardiovascular risk factors, and the effects of such risk factors have been evaluated across several cohorts.1,2 Recently, a heritable component to AF has been reported, and polymorphisms in 3 genetic regions have been reproducibly associated with AF: chromosome 4q25, located 150 kb from the closest gene—a transcription factor (PITX2) involved in cardiac development; chromosome 16q22, intronic to another transcription factor of unknown function, expressed in cardiac tissue (ZFHX3); and an amino acid–altering variant in KCNH2, one of the major cardiac voltage-gated potassium channels.3-5 Rare genetic variants segregating with AF are typically exclusive to individual families and unlikely to contribute to AF prediction at the population level, but genetic polymorphisms could provide important predictive information.