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

E.G. Holliday; J.M. Maguire; T.-J. Evans; S.A. Koblar; J. Jannes; J.W. Sturm; Graeme Hankey; R. Baker; J. Golledge; M.W. Parsons; R. Malik; M. Mcevoy; E. Biros; M.D. Lewis; L.F. Lincz; R. Peel; C. Oldmeadow; W. Smith; P. Moscato; S. Barlera; S. Bevan; J.C. Bis; E. Boerwinkle; G.B. Boncoraglio; T.G. Brott; R.D. Brown; Y.-C. Cheng; J.W. Cole; I. Cotlarciuc; W.J. Devan; M. Fornage; K.L. Furie; S. Grétarsdóttir; A. Gschwendtner; M.A. Ikram; W.T. Longstreth; J.F. Meschia; B.D. Mitchell; T.H. Mosley; M.A. Nalls; E.A. Parati; B.M. Psaty; P. Sharma; K. Stefansson; G. Thorleifsson; U. Thorsteinsdottir; M. Traylor; B.F.J. Verhaaren; K.L. Wiggins; B.B. Worrall; C. Sudlow; P.M. Rothwell; M. Farrall; M. Dichgans; J. Rosand; H.S. Markus; R.J. Scott; C. Levi; J. Attia

doi:10.1038/ng.2397

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

E.G. Holliday, J.M. Maguire, T.-J. Evans, S.A. Koblar, J. Jannes, J.W. Sturm, Graeme Hankey, R. Baker, J. Golledge, M.W. Parsons, R. Malik, M. Mcevoy, E. Biros, M.D. Lewis, L.F. Lincz, R. Peel, C. Oldmeadow, W. Smith, P. Moscato, S. BarleraS. Bevan, J.C. Bis, E. Boerwinkle, G.B. Boncoraglio, T.G. Brott, R.D. Brown, Y.-C. Cheng, J.W. Cole, I. Cotlarciuc, W.J. Devan, M. Fornage, K.L. Furie, S. Grétarsdóttir, A. Gschwendtner, M.A. Ikram, W.T. Longstreth, J.F. Meschia, B.D. Mitchell, T.H. Mosley, M.A. Nalls, E.A. Parati, B.M. Psaty, P. Sharma, K. Stefansson, G. Thorleifsson, U. Thorsteinsdottir, M. Traylor, B.F.J. Verhaaren, K.L. Wiggins, B.B. Worrall, C. Sudlow, P.M. Rothwell, M. Farrall, M. Dichgans, J. Rosand, H.S. Markus, R.J. Scott, C. Levi, J. Attia

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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
Early online date	2 Sept 2012
DOIs	https://doi.org/10.1038/ng.2397
Publication status	Published - 1 Oct 2012

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10.1038/ng.2397

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651583/

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

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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 = "E.G. Holliday and J.M. Maguire and T.-J. Evans and S.A. Koblar and J. Jannes and J.W. Sturm and Graeme Hankey and R. Baker and J. Golledge and M.W. Parsons and R. Malik and M. Mcevoy and E. Biros and M.D. Lewis and L.F. Lincz and R. Peel and C. Oldmeadow and W. Smith and P. Moscato and S. Barlera and S. Bevan and J.C. Bis and E. Boerwinkle and G.B. Boncoraglio and T.G. Brott and R.D. Brown and Y.-C. Cheng and J.W. Cole and I. Cotlarciuc and W.J. Devan and M. Fornage and K.L. Furie and S. Gr{\'e}tarsd{\'o}ttir and A. Gschwendtner and M.A. Ikram and W.T. Longstreth and J.F. Meschia and B.D. Mitchell and T.H. Mosley and M.A. Nalls and E.A. Parati and B.M. Psaty and P. Sharma and K. Stefansson and G. Thorleifsson and U. Thorsteinsdottir and M. Traylor and B.F.J. Verhaaren and K.L. Wiggins and B.B. Worrall and C. Sudlow and P.M. Rothwell and M. Farrall and M. Dichgans and J. Rosand and H.S. Markus and R.J. Scott and C. Levi and J. Attia",

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doi = "10.1038/ng.2397",

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journal = "Nature Genetics",

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Holliday, EG, Maguire, JM, Evans, T-J, Koblar, SA, Jannes, J, Sturm, JW, Hankey, G, 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-C, 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, E.G.

AU - Maguire, J.M.

AU - Evans, T.-J.

AU - Koblar, S.A.

AU - Jannes, J.

AU - Sturm, J.W.

AU - Hankey, Graeme

AU - Baker, R.

AU - Golledge, J.

AU - Parsons, M.W.

AU - Malik, R.

AU - Mcevoy, M.

AU - Biros, E.

AU - Lewis, M.D.

AU - Lincz, L.F.

AU - Peel, R.

AU - Oldmeadow, C.

AU - Smith, W.

AU - Moscato, P.

AU - Barlera, S.

AU - Bevan, S.

AU - Bis, J.C.

AU - Boerwinkle, E.

AU - Boncoraglio, G.B.

AU - Brott, T.G.

AU - Brown, R.D.

AU - Cheng, Y.-C.

AU - Cole, J.W.

AU - Cotlarciuc, I.

AU - Devan, W.J.

AU - Fornage, M.

AU - Furie, K.L.

AU - Grétarsdóttir, S.

AU - Gschwendtner, A.

AU - Ikram, M.A.

AU - Longstreth, W.T.

AU - Meschia, J.F.

AU - Mitchell, B.D.

AU - Mosley, T.H.

AU - Nalls, M.A.

AU - Parati, E.A.

AU - Psaty, B.M.

AU - Sharma, P.

AU - Stefansson, K.

AU - Thorleifsson, G.

AU - Thorsteinsdottir, U.

AU - Traylor, M.

AU - Verhaaren, B.F.J.

AU - Wiggins, K.L.

AU - Worrall, B.B.

AU - Sudlow, C.

AU - Rothwell, P.M.

AU - Farrall, M.

AU - Dichgans, M.

AU - Rosand, J.

AU - Markus, H.S.

AU - Scott, R.J.

AU - Levi, C.

AU - Attia, J.

PY - 2012/10/1

Y1 - 2012/10/1

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

C2 - 22941190

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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