Genome-Wide Association Analysis of Ischemic Stroke in Young Adults

被引：32

作者：

Cheng, Yu-Ching ^{[1
]}

O'Connell, Jeffrey R. ^{[1
]}

Cole, John W. ^{[2
,4
]}

Stine, O. Colin ^{[3
]}

Dueker, Nicole ^{[3
]}

McArdle, Patrick F. ^{[1
]}

Sparks, Mary J. ^{[2
]}

Shen, Jess ^{[5
]}

Laurie, Cathy C. ^{[5
]}

Nelson, Sarah ^{[5
]}

Doheny, Kimberly F. ^{[6
]}

Ling, Hua ^{[6
]}

Pugh, Elizabeth W. ^{[6
]}

Brott, Thomas G. ^{[7
]}

Brown, Robert D., Jr. ^{[8
]}

Meschia, James F. ^{[7
]}

Nalls, Michael ^{[9
]}

Rich, Stephen S. ^{[11
,12
]}

Worrall, Bradford ^{[12
,13
]}

Anderson, Christopher D. ^{[14
,15
,16
]}

Biffi, Alessandro ^{[14
,15
,16
]}

Cortellini, Lynelle ^{[14
,15
,16
]}

Furie, Karen L. ^{[15
]}

Rost, Natalia S. ^{[14
,15
,16
]}

Rosand, Jonathan ^{[14
,15
,16
]}

Manolio, Teri A.

Kittner, Steven J. ^{[2
,4
]}

Mitchell, Braxton D. ^{[1
,10
]}

机构：

[1] Univ Maryland, Dept Med, Sch Med, Baltimore, MD 21201 USA

[2] Univ Maryland, Dept Neurol, Sch Med, Baltimore, MD 21201 USA

[3] Univ Maryland, Dept Epidemiol & Publ Hlth, Sch Med, Baltimore, MD 21201 USA

[4] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MD 21201 USA

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

[6] Johns Hopkins Univ, Ctr Inherited Dis Res, Sch Med, Baltimore, MD 21224 USA

[7] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[8] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA

[9] NIA, Neurogenet Lab, Bethesda, MD 20892 USA

[10] NHGRI, NIH, Bethesda, MD 20892 USA

[11] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA

[12] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA

[13] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA

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

[15] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[16] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA

来源：

G3-GENES GENOMES GENETICS | 2011年 / 1卷 / 06期

基金：

美国国家卫生研究院;

关键词：

epidemiology; genetics; brain infarction; FMNL2; RISK; CLASSIFICATION; IMPUTATION; INFARCTION; VARIANTS; SUBTYPE; DISEASE; LOCI; TOOL;

D O I：

10.1534/g3.111.001164

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

Ischemic stroke (IS) is among the leading causes of death in Western countries. There is a significant genetic component to IS susceptibility, especially among young adults. To date, research to identify genetic loci predisposing to stroke has met only with limited success. We performed a genome-wide association (GWA) analysis of early-onset IS to identify potential stroke susceptibility loci. The GWA analysis was conducted by genotyping 1 million SNPs in a biracial population of 889 IS cases and 927 controls, ages 15-49 years. Genotypes were imputed using the HapMap3 reference panel to provide 1.4 million SNPs for analysis. Logistic regression models adjusting for age, recruitment stages, and population structure were used to determine the association of IS with individual SNPs. Although no single SNP reached genome-wide significance (P < 5 x 10(-8)), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P = 1.2 x 10(-7)) and rs1986743 (in ARL6IP6; P = 2.7 x 10(-7)), strongly associated with early-onset stroke. These data suggest that a novel locus on human chromosome 2q23.3 may be associated with IS susceptibility among young adults.

引用

页码：505 / 513

页数：9

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