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

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, RD; 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

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

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, RD 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

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Publication Type:: Journal Article
Citation:: Nature Genetics, 2012, 44 (10), pp. 1147 - 1151
Issue Date:: 2012-10-01

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Field	Value	Language
dc.contributor.author	Holliday, EG	en_US
dc.contributor.author	Maguire, JM https://orcid.org/0000-0001-5722-8311	en_US
dc.contributor.author	Evans, TJ	en_US
dc.contributor.author	Koblar, SA	en_US
dc.contributor.author	Jannes, J	en_US
dc.contributor.author	Sturm, JW	en_US
dc.contributor.author	Hankey, GJ	en_US
dc.contributor.author	Baker, R	en_US
dc.contributor.author	Golledge, J https://orcid.org/0000-0002-5779-8848	en_US
dc.contributor.author	Parsons, MW	en_US
dc.contributor.author	Malik, R	en_US
dc.contributor.author	McEvoy, M	en_US
dc.contributor.author	Biros, E	en_US
dc.contributor.author	Lewis, MD	en_US
dc.contributor.author	Lincz, LF	en_US
dc.contributor.author	Peel, R	en_US
dc.contributor.author	Oldmeadow, C	en_US
dc.contributor.author	Smith, W	en_US
dc.contributor.author	Moscato, P	en_US
dc.contributor.author	Barlera, S	en_US
dc.contributor.author	Bevan, S	en_US
dc.contributor.author	Bis, JC	en_US
dc.contributor.author	Boerwinkle, E	en_US
dc.contributor.author	Boncoraglio, GB	en_US
dc.contributor.author	Brott, TG	en_US
dc.contributor.author	Brown, RD	en_US
dc.contributor.author	Cheng, YC	en_US
dc.contributor.author	Cole, JW	en_US
dc.contributor.author	Cotlarciuc, I	en_US
dc.contributor.author	Devan, WJ	en_US
dc.contributor.author	Fornage, M	en_US
dc.contributor.author	Furie, KL	en_US
dc.contributor.author	Grétarsdóttir, S	en_US
dc.contributor.author	Gschwendtner, A	en_US
dc.contributor.author	Ikram, MA	en_US
dc.contributor.author	Longstreth, WT	en_US
dc.contributor.author	Meschia, JF	en_US
dc.contributor.author	Mitchell, BD	en_US
dc.contributor.author	Mosley, TH	en_US
dc.contributor.author	Nalls, MA	en_US
dc.contributor.author	Parati, EA	en_US
dc.contributor.author	Psaty, BM	en_US
dc.contributor.author	Sharma, P	en_US
dc.contributor.author	Stefansson, K	en_US
dc.contributor.author	Thorleifsson, G	en_US
dc.contributor.author	Thorsteinsdottir, U	en_US
dc.contributor.author	Traylor, M	en_US
dc.contributor.author	Verhaaren, BFJ	en_US
dc.contributor.author	Wiggins, KL	en_US
dc.contributor.author	Worrall, BB	en_US
dc.contributor.author	Sudlow, C	en_US
dc.contributor.author	Rothwell, PM	en_US
dc.contributor.author	Farrall, M	en_US
dc.contributor.author	Dichgans, M	en_US
dc.contributor.author	Rosand, J	en_US
dc.contributor.author	Markus, HS	en_US
dc.contributor.author	Scott, RJ	en_US
dc.contributor.author	Levi, C	en_US
dc.contributor.author	Attia, J	en_US
dc.date.available	2012-08-09	en_US
dc.date.issued	2012-10-01	en_US
dc.identifier.citation	Nature Genetics, 2012, 44 (10), pp. 1147 - 1151	en_US
dc.identifier.issn	1061-4036	en_US
dc.identifier.uri	http://hdl.handle.net/10453/111327
dc.description.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. © 2012 Nature America, Inc. All rights reserved.	en_US
dc.relation.ispartof	Nature Genetics	en_US
dc.relation.isbasedon	10.1038/ng.2397	en_US
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Chromosomes, Human, Pair 6	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Cerebral Infarction	en_US
dc.subject.mesh	Intracranial Arteriosclerosis	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Odds Ratio	en_US
dc.subject.mesh	Case-Control Studies	en_US
dc.subject.mesh	Linkage Disequilibrium	en_US
dc.subject.mesh	Polymorphism, Single Nucleotide	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.title	Common variants at 6p21.1 are associated with large artery atherosclerotic stroke	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	44	en_US
utslib.for	0604 Genetics	en_US
utslib.for	111706 Epidemiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	44	en_US

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. © 2012 Nature America, Inc. All rights reserved.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/111327