Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

被引：97

作者：

Arking, Dan E. ^{[1
]}

Junttila, M. Juhani ^{[2
,3
]}

Goyette, Philippe ^{[4
,5
]}

Huertas-Vazquez, Adriana ^{[6
]}

Eijgelsheim, Mark ^{[7
]}

Blom, Marieke T. ^{[8
]}

Newton-Cheh, Christopher ^{[9
,10
,11
]}

Reinier, Kyndaron ^{[6
]}

Teodorescu, Carmen ^{[6
]}

Uy-Evanado, Audrey ^{[6
]}

Carter-Monroe, Naima ^{[12
]}

Kaikkonen, Kari S. ^{[2
]}

Kortelainen, Marja-Leena ^{[2
]}

Boucher, Gabrielle ^{[4
,5
]}

Lagace, Caroline ^{[4
,5
]}

Moes, Anna ^{[1
]}

Zhao, XiaoQing ^{[12
]}

Kolodgie, Frank ^{[12
]}

Rivadeneira, Fernando ^{[7
,13
,14
]}

Hofman, Albert ^{[7
,14
]}

Witteman, Jacqueline C. M. ^{[7
,14
]}

Uitterlinden, Andre G. ^{[7
,13
,14
]}

Marsman, Roos F. ^{[8
]}

Pazoki, Raha ^{[8
]}

Bardai, Abdennasser ^{[8
]}

Koster, Rudolph W. ^{[8
]}

Dehghan, Abbas ^{[7
]}

Hwang, Shih-Jen ^{[11
]}

Bhatnagar, Pallav ^{[1
]}

Post, Wendy ^{[15
]}

Hilton, Gina ^{[1
]}

Prineas, Ronald J. ^{[16
]}

Li, Man ^{[17
]}

Koettgen, Anna ^{[17
]}

Ehret, Georg ^{[1
,18
]}

Boerwinkle, Eric ^{[19
]}

Coresh, Josef ^{[17
,20
]}

Kao, W. H. Linda ^{[17
]}

Psaty, Bruce M. ^{[21
,22
]}

Tomaselli, Gordon F. ^{[15
]}

Sotoodehnia, Nona ^{[23
]}

Siscovick, David S. ^{[21
]}

Burke, Greg L. ^{[16
]}

Marban, Eduardo ^{[6
]}

Spooner, Peter M. ^{[15
]}

Cupples, L. Adrienne ^{[11
,24
]}

Jui, Jonathan ^{[25
]}

Gunson, Karen ^{[26
]}

Kesaniemi, Y. Antero ^{[2
,27
]}

Wilde, Arthur A. M. ^{[8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA

[2] Univ Oulu, Dept Internal Med, Inst Clin Med, SF-90220 Oulu, Finland

[3] Univ Miami, Miller Sch Med, Div Cardiol, Miami, FL 33136 USA

[4] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada

[5] Univ Montreal, Montreal, PQ, Canada

[6] Cedars Sinai Med Ctr, Inst Heart, Los Angeles, CA 90048 USA

[7] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[8] Univ Amsterdam, Acad Med Ctr, Heart Failure Res Ctr, Dept Clin & Expt Cardiol, NL-1105 AZ Amsterdam, Netherlands

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

[10] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[11] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA

[12] CVPath Inst, Gaithersburg, MD USA

[13] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[14] NGI, NCHA, Rotterdam, Netherlands

[15] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA

[16] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA

[17] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[18] Univ Hosp Geneva, Dept Med, Geneva, Switzerland

[19] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA

[20] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA

[21] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[22] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA

[23] Univ Washington, Dept Med, Div Cardiol, Cardiovasc Hlth Res Unit, Seattle, WA USA

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

[25] Oregon Hlth & Sci Univ, Dept Emergency Med, Portland, OR 97201 USA

[26] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA

[27] Univ Oulu, Bioctr Oulu, Oulu, Finland

[28] NHLBI, Bethesda, MD 20892 USA

[29] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands

[30] Inspectorate Hlth Care, The Hague, Netherlands

[31] Harvard Univ, Brigham & Womens Hosp, Sch Med,Cardiovasc Div, Ctr Arrhythmia Prevent,Div Prevent Med,Dept Med, Boston, MA 02115 USA

来源：

PLOS GENETICS | 2011年 / 7卷 / 06期

关键词：

ACUTE MYOCARDIAL-INFARCTION; QT INTERVAL DURATION; RESTING HEART-RATE; COMMON VARIANTS; VENTRICULAR-FIBRILLATION; RISK-FACTOR; POPULATION; FAMILY; EPIDEMIOLOGY; BROMODOMAIN;

D O I：

10.1371/journal.pgen.1002158

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8610 210). The risk allele, while ancestral, has a frequency of similar to 1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).

引用

页数：9

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