Genome-wide association analysis of ischemic stroke in young adults

Yu Ching Cheng; Jeffrey R. O'Connell; John W. Cole; O. Colin Stine; Nicole Dueker; Patrick F. McArdle; Mary J. Sparks; Jess Shen; Cathy C. Laurie; Sarah Nelson; Kimberly F. Doheny; Hua Ling; Elizabeth W. Pugh; Thomas G. Brott; Robert D. Brown; James F. Meschia; Michael Nalls; Stephen S. Rich; Bradford Worrall; Christopher D. Anderson; Alessandro Biffi; Lynelle Cortellini; Karen L. Furie; Natalia S. Rost; Jonathan Rosand; Teri A. Manolio; Steven J. Kittner; Braxton D. Mitchell

doi:10.1534/g3.111.001164

Genome-wide association analysis of ischemic stroke in young adults

Yu Ching Cheng, Jeffrey R. O'Connell, John W. Cole, O. Colin Stine, Nicole Dueker, Patrick F. McArdle, Mary J. Sparks, Jess Shen, Cathy C. Laurie, Sarah Nelson, Kimberly F. Doheny, Hua Ling, Elizabeth W. Pugh, Thomas G. Brott, Robert D. Brown, James F. Meschia, Michael Nalls, Stephen S. Rich, Bradford Worrall, Christopher D. AndersonAlessandro Biffi, Lynelle Cortellini, Karen L. Furie, Natalia S. Rost, Jonathan Rosand, Teri A. Manolio, Steven J. Kittner, Braxton D. Mitchell

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

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 × 10^-8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P 1/4 1.2 × 10^-7) and rs1986743 (in ARL6IP6; P 1/4 2.7 × 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.

Original language	English (US)
Pages (from-to)	505-514
Number of pages	10
Journal	G3: Genes, Genomes, Genetics
Volume	1
Issue number	6
DOIs	https://doi.org/10.1534/g3.111.001164
State	Published - Nov 2011

Keywords

Brain infarction
Epidemiology
FMNL2
Genetics

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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10.1534/g3.111.001164

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Cheng, Y. C., O'Connell, J. R., Cole, J. W., Colin Stine, O., Dueker, N., McArdle, P. F., Sparks, M. J., Shen, J., Laurie, C. C., Nelson, S., Doheny, K. F., Ling, H., Pugh, E. W., Brott, T. G., Brown, R. D., Meschia, J. F., Nalls, M., Rich, S. S., Worrall, B., ... Mitchell, B. D. (2011). Genome-wide association analysis of ischemic stroke in young adults. G3: Genes, Genomes, Genetics, 1(6), 505-514. https://doi.org/10.1534/g3.111.001164

Cheng, YC, O'Connell, JR, Cole, JW, Colin Stine, O, Dueker, N, McArdle, PF, Sparks, MJ, Shen, J, Laurie, CC, Nelson, S, Doheny, KF, Ling, H, Pugh, EW, Brott, TG , Brown, RD , Meschia, JF, Nalls, M, Rich, SS, Worrall, B, Anderson, CD, Biffi, A, Cortellini, L, Furie, KL, Rost, NS, Rosand, J, Manolio, TA, Kittner, SJ & Mitchell, BD 2011, 'Genome-wide association analysis of ischemic stroke in young adults', G3: Genes, Genomes, Genetics, vol. 1, no. 6, pp. 505-514. https://doi.org/10.1534/g3.111.001164

@article{ed9ec72ef80f4fc1b598d3132368b367,

title = "Genome-wide association analysis of ischemic stroke in young adults",

abstract = "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 × 10-8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P 1/4 1.2 × 10-7) and rs1986743 (in ARL6IP6; P 1/4 2.7 × 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.",

keywords = "Brain infarction, Epidemiology, FMNL2, Genetics",

author = "Cheng, {Yu Ching} and O'Connell, {Jeffrey R.} and Cole, {John W.} and {Colin Stine}, O. and Nicole Dueker and McArdle, {Patrick F.} and Sparks, {Mary J.} and Jess Shen and Laurie, {Cathy C.} and Sarah Nelson and Doheny, {Kimberly F.} and Hua Ling and Pugh, {Elizabeth W.} and Brott, {Thomas G.} and Brown, {Robert D.} and Meschia, {James F.} and Michael Nalls and Rich, {Stephen S.} and Bradford Worrall and Anderson, {Christopher D.} and Alessandro Biffi and Lynelle Cortellini and Furie, {Karen L.} and Rost, {Natalia S.} and Jonathan Rosand and Manolio, {Teri A.} and Kittner, {Steven J.} and Mitchell, {Braxton D.}",

year = "2011",

month = nov,

doi = "10.1534/g3.111.001164",

language = "English (US)",

volume = "1",

pages = "505--514",

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T1 - Genome-wide association analysis of ischemic stroke in young adults

AU - Cheng, Yu Ching

AU - O'Connell, Jeffrey R.

AU - Cole, John W.

AU - Colin Stine, O.

AU - Dueker, Nicole

AU - McArdle, Patrick F.

AU - Sparks, Mary J.

AU - Shen, Jess

AU - Laurie, Cathy C.

AU - Nelson, Sarah

AU - Doheny, Kimberly F.

AU - Ling, Hua

AU - Pugh, Elizabeth W.

AU - Brott, Thomas G.

AU - Brown, Robert D.

AU - Meschia, James F.

AU - Nalls, Michael

AU - Rich, Stephen S.

AU - Worrall, Bradford

AU - Anderson, Christopher D.

AU - Biffi, Alessandro

AU - Cortellini, Lynelle

AU - Furie, Karen L.

AU - Rost, Natalia S.

AU - Rosand, Jonathan

AU - Manolio, Teri A.

AU - Kittner, Steven J.

AU - Mitchell, Braxton D.

PY - 2011/11

Y1 - 2011/11

N2 - 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 × 10-8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P 1/4 1.2 × 10-7) and rs1986743 (in ARL6IP6; P 1/4 2.7 × 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.

AB - 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 × 10-8), we identified two SNPs in chromosome 2q23.3, rs2304556 (in FMNL2; P 1/4 1.2 × 10-7) and rs1986743 (in ARL6IP6; P 1/4 2.7 × 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.

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KW - Epidemiology

KW - FMNL2

KW - Genetics

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Genome-wide association analysis of ischemic stroke in young adults

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