@article {8557,
	title = {{Genetic Risk Prediction of Atrial Fibrillation},
	journal = {Circulation},
	volume = {135},
	year = {2017},
	month = {Apr},
	pages = {1311{\textendash}1320},
	abstract = {Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke.\ To determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in 5 prospective studies comprising 18 919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40\%]) and 3028 referents. Scores were based on 11 to 719 common variants ({\^a}{\textperthousand}{\textyen}5\%) associated with AF at P values ranging from <1{\~A}{\textemdash}10-3 to <1{\~A}{\textemdash}10-8 in a prior independent genetic association study.\ Incident AF occurred in 1032 individuals (5.5\%). AF genetic risk scores were associated with new-onset AF after adjustment for clinical risk factors. The pooled hazard ratio for incident AF for the highest versus lowest quartile of genetic risk scores ranged from 1.28 (719 variants; 95\% confidence interval, 1.13-1.46; P=1.5{\~A}{\textemdash}10-4) to 1.67 (25 variants; 95\% confidence interval, 1.47-1.90; P=9.3{\~A}{\textemdash}10-15). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum {\^I}{\textquotedblright}C statistic from clinical score alone, 0.009-0.017). AF genetic risk was associated with stroke in age- and sex-adjusted models. For example, individuals in the highest versus lowest quartile of a 127-variant score had a 2.49-fold increased odds of cardioembolic stroke (95\% confidence interval, 1.39-4.58; P=2.7{\~A}{\textemdash}10-3). The effect persisted after the exclusion of individuals (n=70) with known AF (odds ratio, 2.25; 95\% confidence interval, 1.20-4.40; P=0.01).\ Comprehensive AF genetic risk scores were associated with incident AF beyond associations for clinical AF risk factors but offered small improvements in discrimination. AF genetic risk was also associated with cardioembolic stroke in age- and sex-adjusted analyses. Efforts are warranted to determine whether AF genetic risk may improve identification of subclinical AF or help distinguish between stroke mechanisms.},
	author = {Lubitz, S. A. and Yin, X. and Lin, H. J. and Kolek, M. and Smith, J. G. and Trompet, S. and Rienstra, M. and Rost, N. S. and Teixeira, P. L. and Almgren, P. and Anderson, C. D. and Chen, L. Y. and Engstr?m, G. and Ford, I. and Furie, K. L. and Guo, X. and Larson, M. G. and Lunetta, K. L. and Macfarlane, P. W. and Psaty, B. M. and Soliman, E. Z. and Sotoodehnia, N. and Stott, D. J. and Taylor, K. D. and Weng, L. C. and Yao, J. and Geelhoed, B. and Verweij, N. and Siland, J. E. and Kathiresan, S. and Roselli, C. and Roden, D. M. and van der Harst, P. and Darbar, D. and Jukema, J. W. and Melander, O. and Rosand, J. and Rotter, J. I. and Heckbert, S. R. and Ellinor, P. T. and Alonso, A. and Benjamin, E. J.}
}
