Genetic Investigation Into the Differential Risk of Atrial Fibrillation Among Black and White Individuals

被引：35

作者：

Roberts, Jason D. ^{[1
]}

Hu, Donglei ^{[2
,3
]}

Heckbert, Susan R. ^{[4
]}

Alonso, Alvaro ^{[5
]}

Dewland, Thomas A. ^{[1
]}

Vittinghoff, Eric ^{[6
]}

Liu, Yongmei ^{[7
]}

Psaty, Bruce M. ^{[4
,8
,9
,10
,11
]}

Olgin, Jeffrey E. ^{[1
]}

Magnani, Jared W. ^{[12
]}

Huntsman, Scott ^{[2
,3
]}

Burchard, Esteban G. ^{[3
,13
]}

Arking, Dan E. ^{[14
]}

Bibbins-Domingo, Kirsten ^{[3
]}

Harris, Tamara B. ^{[15
]}

Perez, Marco V. ^{[16
]}

Ziv, Elad ^{[2
,3
]}

Marcus, Gregory M. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Med, Div Cardiol, Sect Cardiac Electrophysiol, 505 Parnassus Ave,M1180B, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Med, San Francisco, CA USA

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

[5] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA

[6] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[7] Wake Forest Sch Med, Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA

[8] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[9] Univ Washington, Dept Med, Seattle, WA USA

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

[11] Grp Hlth, Res Inst, Seattle, WA USA

[12] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA

[13] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA

[14] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA

[15] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA

[16] Stanford Univ, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA

来源：

JAMA CARDIOLOGY | 2016年 / 1卷 / 04期

基金：

美国国家卫生研究院;

关键词：

ASSOCIATION; VARIANTS; ANCESTRY; DISEASE; METAANALYSIS; MORTALITY; CANCER; LOCUS; ZFHX3;

D O I：

10.1001/jamacardio.2016.1185

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

IMPORTANCE White persons have a higher risk of atrial fibrillation (AF) compared with black individuals despite a lower prevalence of risk factors. This difference may be due, at least in part, to genetic factors. OBJECTIVES To determine whether 9 single-nucleotide polymorphisms (SNPs) associated with AF account for this paradoxical differential racial risk for AF and to use admixture mapping to search genome-wide for loci that may account for this phenomenon. DESIGN, SETTING, AND PARTICIPANTS Genome-wide admixture analysis and candidate SNP study involving 3 population-based cohort studies that were initiated between 1987 and 1997, including the Cardiovascular Health Study (CHS) (n = 4173), the Atherosclerosis Risk in Communities (ARIC) (n = 12 341) study, and the Health, Aging, and Body Composition (Health ABC) (n = 1015) study. In all 3 studies, race was self-identified. Cox proportional hazards regression models and the proportion of treatment effectmethod were used to determine the impact of 9 AF-risk SNPs among participants from CHS and the ARIC study. The present study began July 1, 2012, and was completed in 2015. MAIN OUTCOMES AND MEASURES Incident AF systematically ascertained using clinic visit electrocardiograms, hospital discharge diagnosis codes, death certificates, and Medicare claims data. RESULTS A single SNP, rs10824026 (chromosome 10: position 73661450), was found to significantly mediate the higher risk for AF in white participants compared with black participants in CHS (11.4%; 95% CI, 2.9%-29.9%) and ARIC (31.7%; 95% CI, 16.0%-53.0%). Admixture mapping was performed in ameta-analysis of black participants within CHS (n = 811), ARIC (n = 3112), and Health ABC (n = 1015). No loci that reached the prespecified statistical threshold for genome-wide significance were identified. CONCLUSIONS AND RELEVANCE The rs10824026 SNP on chromosome 10q22 mediates a modest proportion of the increased risk of AF among white individuals compared with black individuals, potentially through an effect on gene expression levels of MYOZ1. No additional genetic variants accounting for a significant portion of the differential racial risk of AF were identified with genome-wide admixture mapping, suggesting that additional genetic or environmental influences beyond single SNPs in isolation may account for the paradoxical racial risk of AF among white individuals and black individuals.

引用

页码：442 / 450

页数：9

共 40 条

[1] Incidence of atrial fibrillation in whites and African-Americans: The Atherosclerosis Risk in Communities (ARIC) study [J].

Alonso, Alvaro ;

Agarwal, Sunil K. ;

Soliman, Elsayed Z. ;

Ambrose, Marietta ;

Chamberlain, Alanna M. ;

Prineas, Ronald J. ;

Folsom, Aaron R. .

AMERICAN HEART JOURNAL, 2009, 158 (01) :111-117

[2] Association of Major and Minor ECG Abnormalities With Coronary Heart Disease Events [J].

Auer, Reto ;

Bauer, Douglas C. ;

Marques-Vidal, Pedro ;

Butler, Javed ;

Min, Lauren J. ;

Cornuz, Jacques ;

Satterfield, Suzanne ;

Newman, Anne B. ;

Vittinghoff, Eric ;

Rodondi, Nicolas .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2012, 307 (14) :1497-1505

[3] Fast and accurate inference of local ancestry in Latino populations [J].

Baran, Yael ;

Pasaniuc, Bogdan ;

Sankararaman, Sriram ;

Torgerson, Dara G. ;

Gignoux, Christopher ;

Eng, Celeste ;

Rodriguez-Cintron, William ;

Chapela, Rocio ;

Ford, Jean G. ;

Avila, Pedro C. ;

Rodriguez-Santana, Jose ;

Burchard, Esteban Gonzalez ;

Halperin, Eran .

BIOINFORMATICS, 2012, 28 (10) :1359-1367

[4] Impact of atrial fibrillation on the risk of death [J].

Benjamin, EJ ;

Wolf, PA ;

D'Agostino, RB ;

Silbershatz, H ;

Kannel, WB ;

Levy, D .

CIRCULATION, 1998, 98 (10) :946-952

[5] Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry [J].

Benjamin, Emelia J. ;

Rice, Kenneth M. ;

Arking, Dan E. ;

Pfeufer, Arne ;

van Noord, Charlotte ;

Smith, Albert V. ;

Schnabel, Renate B. ;

Bis, Joshua C. ;

Boerwinkle, Eric ;

Sinner, Moritz F. ;

Dehghan, Abbas ;

Lubitz, Steven A. ;

D'Agostino, Ralph B., Sr. ;

Lumley, Thomas ;

Ehret, Georg B. ;

Heeringa, Jan ;

Aspelund, Thor ;

Newton-Cheh, Christopher ;

Larson, Martin G. ;

Marciante, Kristin D. ;

Soliman, Elsayed Z. ;

Rivadeneira, Fernando ;

Wang, Thomas J. ;

Eiriksdottir, Gudny ;

Levy, Daniel ;

Psaty, Bruce M. ;

Li, Man ;

Chamberlain, Alanna M. ;

Hofman, Albert ;

Vasan, Ramachandran S. ;

Harris, Tamara B. ;

Rotter, Jerome I. ;

Kao, W. H. Linda ;

Agarwal, Sunil K. ;

Stricker, Bruno H. Ch ;

Wang, Ke ;

Launer, Lenore J. ;

Smith, Nicholas L. ;

Chakravarti, Aravinda ;

Uitterlinden, Andre G. ;

Wolf, Philip A. ;

Sotoodehnia, Nona ;

Koettgen, Anna ;

van Duijn, Cornelia M. ;

Meitinger, Thomas ;

Mueller, Martina ;

Perz, Siegfried ;

Steinbeck, Gerhard ;

Wichmann, H-Erich ;

Lunetta, Kathryn L. .

NATURE GENETICS, 2009, 41 (08) :879-881

[6]

Delaneau O, 2012, NAT METHODS, V9, P179, DOI [10.1038/NMETH.1785, 10.1038/nmeth.1785]

[7] Single-Nucleotide Polymorphisms in LPA Explain Most of the Ancestry-Specific Variation in Lp(a) Levels in African Americans [J].

Deo, Rahul C. ;

Wilson, James G. ;

Xing, Chao ;

Lawson, Kim ;

Kao, W. H. Linda ;

Reich, David ;

Tandon, Arti ;

Akylbekova, Ermeg ;

Patterson, Nick ;

Mosley, Thomas H., Jr. ;

Boerwinkle, Eric ;

Taylor, Herman A., Jr. .

PLOS ONE, 2011, 6 (01)

[8] Incident Atrial Fibrillation Among Asians, Hispanics, Blacks, and Whites [J].

Dewland, Thomas A. ;

Olgin, Jeffrey E. ;

Vittinghoff, Eric ;

Marcus, Gregory M. .

CIRCULATION, 2013, 128 (23) :2470-2477

[9] Meta-analysis identifies six new susceptibility loci for atrial fibrillation [J].

Ellinor, Patrick T. ;

Lunetta, Kathryn L. ;

Albert, Christine M. ;

Glazer, Nicole L. ;

Ritchie, Marylyn D. ;

Smith, Albert V. ;

Arking, Dan E. ;

Mueller-Nurasyid, Martina ;

Krijthe, Bouwe P. ;

Lubitz, Steven A. ;

Bis, Joshua C. ;

Chung, Mina K. ;

Doerr, Marcus ;

Ozaki, Kouichi ;

Roberts, Jason D. ;

Smith, J. Gustav ;

Pfeufer, Arne ;

Sinner, Moritz F. ;

Lohman, Kurt ;

Ding, Jingzhong ;

Smith, Nicholas L. ;

Smith, Jonathan D. ;

Rienstra, Michiel ;

Rice, Kenneth M. ;

Van Wagoner, David R. ;

Magnani, Jared W. ;

Wakili, Reza ;

Clauss, Sebastian ;

Rotter, Jerome I. ;

Steinbeck, Gerhard ;

Launer, Lenore J. ;

Davies, Robert W. ;

Borkovich, Matthew ;

Harris, Tamara B. ;

Lin, Honghuang ;

Voelker, Uwe ;

Voelzke, Henry ;

Milan, David J. ;

Hofman, Albert ;

Boerwinkle, Eric ;

Chen, Lin Y. ;

Soliman, Elsayed Z. ;

Voight, Benjamin F. ;

Li, Guo ;

Chakravarti, Aravinda ;

Kubo, Michiaki ;

Tedrow, Usha B. ;

Rose, Lynda M. ;

Ridker, Paul M. ;

Conen, David .

NATURE GENETICS, 2012, 44 (06) :670-U88

[10] Common variants in KCNN3 are associated with lone atrial fibrillation [J].

Ellinor, Patrick T. ;

Lunetta, Kathryn L. ;

Glazer, Nicole L. ;

Pfeufer, Arne ;

Alonso, Alvaro ;

Chung, Mina K. ;

Sinner, Moritz F. ;

de Bakker, Paul I. W. ;

Mueller, Martina ;

Lubitz, Steven A. ;

Fox, Ervin ;

Darbar, Dawood ;

Smith, Nicholas L. ;

Smith, Jonathan D. ;

Schnabel, Renate B. ;

Soliman, Elsayed Z. ;

Rice, Kenneth M. ;

Van Wagoner, David R. ;

Beckmann, Britt-M ;

van Noord, Charlotte ;

Wang, Ke ;

Ehret, Georg B. ;

Rotter, Jerome I. ;

Hazen, Stanley L. ;

Steinbeck, Gerhard ;

Smith, Albert V. ;

Launer, Lenore J. ;

Harris, Tamara B. ;

Makino, Seiko ;

Nelis, Mari ;

Milan, David J. ;

Perz, Siegfried ;

Esko, Tonu ;

Koettgen, Anna ;

Moebus, Susanne ;

Newton-Cheh, Christopher ;

Li, Man ;

Moehlenkamp, Stefan ;

Wang, Thomas J. ;

Kao, W. H. Linda ;

Vasan, Ramachandran S. ;

Noethen, Markus M. ;

MacRae, Calum A. ;

Stricker, Bruno H. Ch ;

Hofman, Albert ;

Uitterlinden, Andre G. ;

Levy, Daniel ;

Boerwinkle, Eric ;

Metspalu, Andres ;

Topol, Eric J. .

NATURE GENETICS, 2010, 42 (03) :240-U36

← 1 2 3 4 →