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 Jr. 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, Cathie Sudlow, Peter M. Rothwell, Martin Farrall, Martin Dichgans, Jonathan Rosand, Hugh S. Markus, Rodney J. Scott, Christopher Levi, John Attia

Research output: Contribution to journalArticle

112 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1147-1151
Number of pages5
JournalNature Genetics
Volume44
Issue number10
DOIs
StatePublished - Oct 2012

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Atherosclerosis
Arteries
Stroke
Population Control
Genome-Wide Association Study
Odds Ratio
Genetic Loci
Meta-Analysis
Cohort Studies
Chromosomes
Alleles
Population

ASJC Scopus subject areas

  • Genetics

Cite this

Holliday, E. G., Maguire, J. M., Evans, T. J., Koblar, S. A., Jannes, J., Sturm, J. W., ... 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

Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. / Holliday, Elizabeth G.; Maguire, Jane M.; Evans, Tiffany Jane; Koblar, Simon A.; Jannes, Jim; Sturm, Jonathan W.; Hankey, Graeme J.; Baker, Ross; Golledge, Jonathan; Parsons, Mark W.; Malik, Rainer; McEvoy, Mark; Biros, Erik; Lewis, Martin D.; Lincz, Lisa F.; Peel, Roseanne; Oldmeadow, Christopher; Smith, Wayne; Moscato, Pablo; Barlera, Simona; Bevan, Steve; Bis, Joshua C.; Boerwinkle, Eric; Boncoraglio, Giorgio B.; Brott, Thomas G; Brown, Robert D Jr.; Cheng, Yu Ching; Cole, John W.; Cotlarciuc, Ioana; Devan, William J.; Fornage, Myriam; Furie, Karen L.; Grétarsdóttir, Sólveig; Gschwendtner, Andreas; Ikram, M. Arfan; Longstreth, W. T.; Meschia, James F; Mitchell, Braxton D.; Mosley, Thomas H.; Nalls, Michael A.; Parati, Eugenio A.; Psaty, Bruce M.; Sharma, Pankaj; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Traylor, Matthew; Verhaaren, Benjamin F J; Wiggins, Kerri L.; Worrall, Bradford B.; Sudlow, Cathie; Rothwell, Peter M.; Farrall, Martin; Dichgans, Martin; Rosand, Jonathan; Markus, Hugh S.; Scott, Rodney J.; Levi, Christopher; Attia, John.

In: Nature Genetics, Vol. 44, No. 10, 10.2012, p. 1147-1151.

Research output: Contribution to journalArticle

Holliday, EG, Maguire, JM, Evans, TJ, 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, RDJ, Cheng, YC, 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
Holliday EG, Maguire JM, Evans TJ, Koblar SA, Jannes J, Sturm JW et al. Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. Nature Genetics. 2012 Oct;44(10):1147-1151. https://doi.org/10.1038/ng.2397
Holliday, Elizabeth G. ; Maguire, Jane M. ; Evans, Tiffany Jane ; Koblar, Simon A. ; Jannes, Jim ; Sturm, Jonathan W. ; Hankey, Graeme J. ; Baker, Ross ; Golledge, Jonathan ; Parsons, Mark W. ; Malik, Rainer ; McEvoy, Mark ; Biros, Erik ; Lewis, Martin D. ; Lincz, Lisa F. ; Peel, Roseanne ; Oldmeadow, Christopher ; Smith, Wayne ; Moscato, Pablo ; Barlera, Simona ; Bevan, Steve ; Bis, Joshua C. ; Boerwinkle, Eric ; Boncoraglio, Giorgio B. ; Brott, Thomas G ; Brown, Robert D Jr. ; Cheng, Yu Ching ; Cole, John W. ; Cotlarciuc, Ioana ; Devan, William J. ; Fornage, Myriam ; Furie, Karen L. ; Grétarsdóttir, Sólveig ; Gschwendtner, Andreas ; Ikram, M. Arfan ; Longstreth, W. T. ; Meschia, James F ; Mitchell, Braxton D. ; Mosley, Thomas H. ; Nalls, Michael A. ; Parati, Eugenio A. ; Psaty, Bruce M. ; Sharma, Pankaj ; Stefansson, Kari ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Traylor, Matthew ; Verhaaren, Benjamin F J ; Wiggins, Kerri L. ; Worrall, Bradford B. ; Sudlow, Cathie ; Rothwell, Peter M. ; Farrall, Martin ; Dichgans, Martin ; Rosand, Jonathan ; Markus, Hugh S. ; Scott, Rodney J. ; Levi, Christopher ; Attia, John. / Common variants at 6p21.1 are associated with large artery atherosclerotic stroke. In: Nature Genetics. 2012 ; Vol. 44, No. 10. pp. 1147-1151.
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AU - Holliday, Elizabeth G.

AU - Maguire, Jane M.

AU - Evans, Tiffany Jane

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AU - Sturm, Jonathan W.

AU - Hankey, Graeme J.

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AU - Golledge, Jonathan

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AU - Malik, Rainer

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AU - Gschwendtner, Andreas

AU - Ikram, M. Arfan

AU - Longstreth, W. T.

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AU - Mitchell, Braxton D.

AU - Mosley, Thomas H.

AU - Nalls, Michael A.

AU - Parati, Eugenio A.

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AU - Rothwell, Peter M.

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AU - Dichgans, Martin

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