Genetic Risk Prediction of Atrial Fibrillation

被引：78

作者：

Lubitz, Steven A. ^{[1
,2
,5
]}

Yin, Xiaoyan ^{[6
,7
]}

Lin, Henry J. ^{[8
,9
]}

Kolek, Matthew ^{[10
]}

Smith, J. Gustav ^{[11
,12
]}

Trompet, Stella ^{[13
,14
]}

Rienstra, Michiel ^{[15
]}

Rost, Natalia S. ^{[3
]}

Teixeira, Pedro L. ^{[10
]}

Almgren, Peter ^{[16
]}

Anderson, Christopher D. ^{[3
,4
,5
]}

Chen, Lin Y. ^{[17
]}

Engstrom, Gunnar ^{[16
]}

Ford, Ian ^{[18
]}

Furie, Karen L. ^{[20
]}

Guo, Xiuqing ^{[8
,9
]}

Larson, Martin G. ^{[6
,7
,21
,22
]}

Lunetta, Kathryn L. ^{[6
,7
,22
]}

Macfarlane, Peter W. ^{[19
]}

Psaty, Bruce M. ^{[26
,27
,28
,29
]}

Soliman, Elsayed Z. ^{[30
]}

Sotoodehnia, Nona ^{[26
,27
]}

Stott, David J. ^{[19
]}

Taylor, Kent D. ^{[8
,9
]}

Weng, Lu-Chen ^{[2
,5
]}

Yao, Jie ^{[9
]}

Geelhoed, Bastiaan ^{[15
]}

Verweij, Niek ^{[15
]}

Siland, Joylene E. ^{[15
]}

Kathiresan, Sekar ^{[2
,4
,5
]}

Roselli, Carolina ^{[5
]}

Roden, Dan M. ^{[31
]}

van der Harst, Pim ^{[15
]}

Darbar, Dawood ^{[10
,32
]}

Jukema, J. Wouter ^{[13
,33
]}

Melander, Olle ^{[16
,34
]}

Rosand, Jonathan ^{[3
,4
,5
]}

Rotter, Jerome I. ^{[8
,9
]}

Heckbert, Susan R. ^{[26
,27
,29
]}

Ellinor, Patrick T. ^{[1
,2
,5
]}

Alonso, Alvaro ^{[35
]}

Benjamin, Emelia J. ^{[6
,7
,23
,24
,25
]}

机构：

[1] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 55 Fruit St,GRB 109, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[5] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA

[6] Boston Univ, Boston, MA 02215 USA

[7] NHLBI, Framingham Heart Study, Framingham, MA USA

[8] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA

[9] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA

[10] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA

[11] Lund Univ, Dept Cardiol, Clin Sci, Malmo, Sweden

[12] Skane Univ Hosp, Lund, Sweden

[13] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands

[14] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands

[15] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands

[16] Lund Univ, Dept Clin Sci, Malmo, Sweden

[17] Univ Minnesota, Div Cardiovasc, Dept Med, Sch Med, Minneapolis, MN 55455 USA

[18] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland

[19] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland

[20] Brown Univ, Rhode Isl Hosp, Dept Neurol, Alpert Med Sch, Providence, RI 02903 USA

[21] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[22] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA

[23] Boston Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02215 USA

[24] Boston Univ, Sect Cardiovasc Med, Dept Med, Sch Publ Hlth, Boston, MA 02215 USA

[25] Boston Univ, Prevent Med Sect, Dept Med, Sch Publ Hlth, Boston, MA 02215 USA

[26] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[27] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[28] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[29] Kaiser Permanente, Hlth Res Inst, Seattle, WA USA

[30] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr EPICARE, Winston Salem, NC USA

[31] Vanderbilt Univ, Sch Med, Dept Med & Mol Physiol & Biophys, Nashville, TN 37212 USA

[32] Univ Illinois, Chicago, IL USA

[33] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands

[34] Skane Univ Hosp, Dept Internal Med, Malmo, Sweden

[35] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

来源：

CIRCULATION | 2017年 / 135卷 / 14期

基金：

欧盟地平线“2020”;

关键词：

atrial fibrillation; atrial flutter; forecasting; genetic association studies; stroke; GENOME-WIDE ASSOCIATION; ISCHEMIC-STROKE; AFRICAN-AMERICANS; COMMON VARIANTS; HEART; METAANALYSIS; INDIVIDUALS; SEQUENCE; DISEASE; MODEL;

D O I：

10.1161/CIRCULATIONAHA.116.024143

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND: Atrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke. METHODS: 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 (>= 5%) associated with AF at P values ranging from <1x10(-3) to <1x10(-8) in a prior independent genetic association study. RESULTS: 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=1.5x10(-4)) to 1.67 (25 variants; 95% confidence interval, 1.47-1.90; P=9.3x10(-15)). Discrimination of combined clinical and genetic risk scores varied across studies and scores (maximum C statistic, 0.629-0.811; maximum Delta 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=2.7x10(-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). CONCLUSIONS: 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.

引用

页码：1311 / +

页数：37

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