Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

Elizabeth G Holliday; Jane M Maguire; Tiffany-jane Evans; Simon A Koblar; Jim Jannes; Jonathan W Sturm; Graeme J Hankey; Ross Baker; Jonathan Golledge; Mark W Parsons; Rainer Malik; Mark Mcevoy; Erik Biros; Martin D Lewis; Lisa F Lincz; Roseanne Peel; Christopher Oldmeadow; Wayne Smith; Pablo Moscato; Simona Barlera; Steve Bevan; Joshua C Bis; Eric Boerwinkle; Giorgio B Boncoraglio; Thomas G Brott; Robert D Brown; Yu-ching Cheng; John W Cole; Ioana Cotlarciuc; William J Devan; Myriam Fornage; Karen L Furie; Sólveig Grétarsdóttir; Andreas Gschwendtner; M Arfan Ikram; W T Longstreth; James F Meschia; Braxton D Mitchell; Thomas H Mosley; Michael A Nalls; Eugenio A Parati; Bruce M Psaty; Pankaj Sharma; Kari Stefansson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Matthew Traylor; Benjamin F J Verhaaren; Kerri L Wiggins; Bradford B Worrall; Catherine Sudlow; Peter M Rothwell; Martin Farrall; Martin Dichgans; Jonathan Rosand; Hugh S Markus; Rodney J Scott; Christopher Levi; John Attia

doi:10.1038/ng.2397

Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

Elizabeth G Holliday, Jane M Maguire, Tiffany-jane Evans, Simon A Koblar, Jim Jannes, Jonathan W Sturm, Graeme J Hankey, Ross Baker, Jonathan Golledge, Mark W Parsons, Rainer Malik, Mark Mcevoy, Erik Biros, Martin D Lewis, Lisa F Lincz, Roseanne Peel, Christopher Oldmeadow, Wayne Smith, Pablo Moscato, Simona BarleraSteve Bevan, Joshua C Bis, Eric Boerwinkle, Giorgio B Boncoraglio, Thomas G Brott, Robert D Brown, Yu-ching Cheng, John W Cole, Ioana Cotlarciuc, William J Devan, Myriam Fornage, Karen L Furie, Sólveig Grétarsdóttir, Andreas Gschwendtner, M Arfan Ikram, W T Longstreth, James F Meschia, Braxton D Mitchell, Thomas H Mosley, Michael A Nalls, Eugenio A Parati, Bruce M Psaty, Pankaj Sharma, Kari Stefansson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Matthew Traylor, Benjamin F J Verhaaren, Kerri L Wiggins, Bradford B Worrall, Catherine Sudlow, Peter M Rothwell, Martin Farrall, Martin Dichgans, Jonathan Rosand, Hugh S Markus, Rodney J Scott, Christopher Levi, John Attia

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

Abstract

Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9×10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9×10(-4); discovery and replication combined OR=1.21, P=4.7×10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke

Original language	English
Pages (from-to)	1147-1151
Journal	Nature Genetics
Volume	44
Issue number	10
DOIs	https://doi.org/10.1038/ng.2397
Publication status	Published - 2012

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10.1038/ng.2397

Common variants at 6p21.1 are associated with large artery atherosclerotic stroke
Published in final edited form as: Nat Genet. 2012 October; 44(10): 10.1038/ng.2397. Published online 2012 September 2. doi: 10.1038/ng.239
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Holliday, E. G., Maguire, J. M., Evans, T., Koblar, S. A., Jannes, J., Sturm, J. W., Hankey, G. J., Baker, R., Golledge, J., Parsons, M. W., Malik, R., Mcevoy, M., Biros, E., Lewis, M. D., Lincz, L. F., Peel, R., Oldmeadow, C., Smith, W., Moscato, P., ... Attia, J. (2012). Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nature Genetics, 44(10), 1147-1151. https://doi.org/10.1038/ng.2397

@article{9f087df351b845db95d009240c611e79,

title = "Common variants at 6p21.1 are associated with large artery atherosclerotic stroke",

abstract = "Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9×10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9×10(-4); discovery and replication combined OR=1.21, P=4.7×10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke",

author = "Holliday, {Elizabeth G} and Maguire, {Jane M} and Tiffany-jane Evans and Koblar, {Simon A} and Jim Jannes and Sturm, {Jonathan W} and Hankey, {Graeme J} and Ross Baker and Jonathan Golledge and Parsons, {Mark W} and Rainer Malik and Mark Mcevoy and Erik Biros and Lewis, {Martin D} and Lincz, {Lisa F} and Roseanne Peel and Christopher Oldmeadow and Wayne Smith and Pablo Moscato and Simona Barlera and Steve Bevan and Bis, {Joshua C} and Eric Boerwinkle and Boncoraglio, {Giorgio B} and Brott, {Thomas G} and Brown, {Robert D} and Yu-ching Cheng and Cole, {John W} and Ioana Cotlarciuc and Devan, {William J} and Myriam Fornage and Furie, {Karen L} and S{\'o}lveig Gr{\'e}tarsd{\'o}ttir and Andreas Gschwendtner and Ikram, {M Arfan} and Longstreth, {W T} and Meschia, {James F} and Mitchell, {Braxton D} and Mosley, {Thomas H} and Nalls, {Michael A} and Parati, {Eugenio A} and Psaty, {Bruce M} and Pankaj Sharma and Kari Stefansson and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Matthew Traylor and Verhaaren, {Benjamin F J} and Wiggins, {Kerri L} and Worrall, {Bradford B} and Catherine Sudlow and Rothwell, {Peter M} and Martin Farrall and Martin Dichgans and Jonathan Rosand and Markus, {Hugh S} and Scott, {Rodney J} and Christopher Levi and John Attia",

year = "2012",

doi = "10.1038/ng.2397",

language = "English",

volume = "44",

pages = "1147--1151",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "10",

}

Holliday, EG, Maguire, JM, Evans, T, Koblar, SA, Jannes, J, Sturm, JW, Hankey, GJ, Baker, R, Golledge, J, Parsons, MW, Malik, R, Mcevoy, M, Biros, E, Lewis, MD, Lincz, LF, Peel, R, Oldmeadow, C, Smith, W, Moscato, P, Barlera, S, Bevan, S, Bis, JC, Boerwinkle, E, Boncoraglio, GB, Brott, TG, Brown, RD, Cheng, Y, Cole, JW, Cotlarciuc, I, Devan, WJ, Fornage, M, Furie, KL, Grétarsdóttir, S, Gschwendtner, A, Ikram, MA, Longstreth, WT, Meschia, JF, Mitchell, BD, Mosley, TH, Nalls, MA, Parati, EA, Psaty, BM, Sharma, P, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, Traylor, M, Verhaaren, BFJ, Wiggins, KL, Worrall, BB, Sudlow, C, Rothwell, PM, Farrall, M, Dichgans, M, Rosand, J, Markus, HS, Scott, RJ, Levi, C & Attia, J 2012, 'Common variants at 6p21.1 are associated with large artery atherosclerotic stroke', Nature Genetics, vol. 44, no. 10, pp. 1147-1151. https://doi.org/10.1038/ng.2397

TY - JOUR

T1 - Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

AU - Holliday, Elizabeth G

AU - Maguire, Jane M

AU - Evans, Tiffany-jane

AU - Koblar, Simon A

AU - Jannes, Jim

AU - Sturm, Jonathan W

AU - Hankey, Graeme J

AU - Baker, Ross

AU - Golledge, Jonathan

AU - Parsons, Mark W

AU - Malik, Rainer

AU - Mcevoy, Mark

AU - Biros, Erik

AU - Lewis, Martin D

AU - Lincz, Lisa F

AU - Peel, Roseanne

AU - Oldmeadow, Christopher

AU - Smith, Wayne

AU - Moscato, Pablo

AU - Barlera, Simona

AU - Bevan, Steve

AU - Bis, Joshua C

AU - Boerwinkle, Eric

AU - Boncoraglio, Giorgio B

AU - Brott, Thomas G

AU - Brown, Robert D

AU - Cheng, Yu-ching

AU - Cole, John W

AU - Cotlarciuc, Ioana

AU - Devan, William J

AU - Fornage, Myriam

AU - Furie, Karen L

AU - Grétarsdóttir, Sólveig

AU - Gschwendtner, Andreas

AU - Ikram, M Arfan

AU - Longstreth, W T

AU - Meschia, James F

AU - Mitchell, Braxton D

AU - Mosley, Thomas H

AU - Nalls, Michael A

AU - Parati, Eugenio A

AU - Psaty, Bruce M

AU - Sharma, Pankaj

AU - Stefansson, Kari

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Traylor, Matthew

AU - Verhaaren, Benjamin F J

AU - Wiggins, Kerri L

AU - Worrall, Bradford B

AU - Sudlow, Catherine

AU - Rothwell, Peter M

AU - Farrall, Martin

AU - Dichgans, Martin

AU - Rosand, Jonathan

AU - Markus, Hugh S

AU - Scott, Rodney J

AU - Levi, Christopher

AU - Attia, John

PY - 2012

Y1 - 2012

N2 - Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9×10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9×10(-4); discovery and replication combined OR=1.21, P=4.7×10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke

AB - Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR)=1.62, P=3.9×10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR=1.15, P=3.9×10(-4); discovery and replication combined OR=1.21, P=4.7×10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke

U2 - 10.1038/ng.2397

DO - 10.1038/ng.2397

M3 - Article

SN - 1061-4036

VL - 44

SP - 1147

EP - 1151

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

Abstract

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