Genomewide Association Studies of Stroke

被引：355

作者：

Ikram, M. Arfan ^{[1
]}

Seshadri, Sudha ^{[8
]}

Bis, Joshua C. ^{[12
]}

Fornage, Myriam ^{[19
,20
,25
]}

DeStefano, Anita L. ^{[8
,9
]}

Aulchenko, Yurii S. ^{[1
]}

Debette, Stephanie ^{[8
]}

Lumley, Thomas ^{[13
]}

Folsom, Aaron R. ^{[26
,27
]}

van den Herik, Evita G. ^{[2
]}

Bos, Michiel J. ^{[1
,2
]}

Beiser, Alexa ^{[8
,9
]}

Cushman, Mary ^{[21
]}

Launer, Lenore J. ^{[33
]}

Shahar, Eyal ^{[28
]}

Struchalin, Maksim ^{[1
,3
]}

Du, Yangchun ^{[8
,9
]}

Glazer, Nicole L. ^{[12
]}

Rosamond, Wayne D. ^{[29
]}

Rivadeneira, Fernando ^{[4
]}

Kelly-Hayes, Margaret ^{[8
]}

Lopez, Oscar L. ^{[22
,23
]}

Coresh, Josef ^{[30
,31
]}

Hofman, Albert ^{[1
]}

DeCarli, Charles ^{[10
,11
]}

Heckbert, Susan R. ^{[14
,17
]}

Koudstaal, Peter J. ^{[2
]}

Yang, Qiong ^{[9
]}

Smith, Nicholas L. ^{[14
,18
]}

Kase, Carlos S. ^{[8
]}

Rice, Kenneth ^{[13
]}

Haritunians, Talin ^{[24
]}

Roks, Gerwin ^{[6
,7
]}

de Kort, Paul L. M. ^{[6
,7
]}

Taylor, Kent D. ^{[24
]}

de Lau, Lonneke M. ^{[2
]}

Oostra, Ben A. ^{[1
]}

Uitterlinden, Andre G. ^{[1
,4
,5
]}

Rotter, Jerome I. ^{[24
]}

Boerwinkle, Eric ^{[20
,25
]}

Psaty, Bruce M. ^{[12
,14
,15
,17
]}

Mosley, Thomas H. ^{[32
]}

van Duijn, Cornelia M. ^{[1
]}

Breteler, Monique M. B. ^{[1
]}

Longstreth, W. T., Jr. ^{[12
,14
,16
]}

Wolf, Philip A. ^{[8
]}

机构：

[1] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam Study, Rotterdam, Netherlands

[2] Erasmus MC Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[3] Erasmus MC Univ, Med Ctr, Dept Forens Mol Biol, Rotterdam, Netherlands

[4] Erasmus MC Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[5] Erasmus MC Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands

[6] St Elizabeth Hosp, Dept Neurol, Tilburg, Netherlands

[7] TweeSteden Hosp, Dept Neurol, Tilburg, Netherlands

[8] Boston Univ, Sch Med, Dept Neurol, Framingham Heart Study, Boston, MA 02118 USA

[9] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[10] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA

[11] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA

[12] Univ Washington, Dept Med, Cardiovasc Hlth Study, Seattle, WA 98195 USA

[13] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

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

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

[16] Univ Washington, Dept Neurol, Seattle, WA 98195 USA

[17] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA

[18] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off, Res & Dev, Seattle, WA USA

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

[20] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Atherosclerosis Risk Communities Study, Houston, TX USA

[21] Univ Vermont, Dept Pathol & Med, Burlington, VT 05405 USA

[22] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA

[23] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA

[24] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[25] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA

[26] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA

[27] Univ Minnesota, Community Hlth Sch Publ Hlth, Minneapolis, MN 55455 USA

[28] Univ Arizona, Div Epidemiol & Biostat, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA

[29] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[30] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent, Baltimore, MD USA

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

[32] Univ Mississippi, Med Ctr, Dept Geriatr Med, Jackson, MS USA

[33] NIA, Intramural Res Program, Aging Gene Environm Susceptibil Reykjavik Study, Washington, DC USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2009年 / 360卷 / 17期

基金：

美国国家卫生研究院;

关键词：

WNK1; GENE; FOLLOW-UP; WIDE ASSOCIATION; BLOOD-PRESSURE; LIFETIME RISK; FRAMINGHAM; HEART; POPULATION; DESIGN; EPIDEMIOLOGY;

D O I：

10.1056/NEJMoa0900094

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background The genes underlying the risk of stroke in the general population remain undetermined. Methods We carried out an analysis of genomewide association data generated from four large cohorts composing the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, including 19,602 white persons (mean [+/- SD] age, 63 +/- 8 years) in whom 1544 incident strokes (1164 ischemic strokes) developed over an average follow-up of 11 years. We tested the markers most strongly associated with stroke in a replication cohort of 2430 black persons with 215 incident strokes (191 ischemic strokes), another cohort of 574 black persons with 85 incident strokes (68 ischemic strokes), and 652 Dutch persons with ischemic stroke and 3613 unaffected persons. Results Two intergenic single-nucleotide polymorphisms on chromosome 12p13 and within 11 kb of the gene NINJ2 were associated with stroke (P<5x10(-8)). NINJ2 encodes an adhesion molecule expressed in glia and shows increased expression after nerve injury. Direct genotyping showed that rs12425791 was associated with an increased risk of total (i.e., all types) and ischemic stroke, with hazard ratios of 1.30 (95% confidence interval [CI], 1.19 to 1.42) and 1.33 (95% CI, 1.21 to 1.47), respectively, yielding population attributable risks of 11% and 12% in the discovery cohorts. Corresponding hazard ratios were 1.35 (95% CI, 1.01 to 1.79; P = 0.04) and 1.42 (95% CI, 1.06 to 1.91; P = 0.02) in the large cohort of black persons and 1.17 (95% CI, 1.01 to 1.37; P = 0.03) and 1.19 (95% CI, 1.01 to 1.41; P = 0.04) in the Dutch sample; the results of an underpowered analysis of the smaller black cohort were nonsignificant. Conclusions A genetic locus on chromosome 12p13 is associated with an increased risk of stroke.

引用

页码：1718 / 1728

页数：11

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