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Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

Authors :
Traylor, M
Farrall, M
Holliday, EG
Sudlow, C
Hopewell, JC
Cheng, YC
Fornage, M
Ikram, MA
Malik, R
Bevan, S
Thorsteinsdottir, U
Nalls, MA
Longstreth, WT
Wiggins, KL
Yadav, S
Parati, EA
DeStefano, AL
Worrall, BB
Kittner, SJ
Khan, MS
Reiner, AP
Helgadottir, A
Achterberg, S
Fernandez-Cadenas, I
Abboud, S
Schmidt, R
Walters, M
Chen, WM
Ringelstein, EB
O'Donnell, M
Ho, WK
Pera, J
Lemmens, R
Norrving, B
Higgins, P
Benn, M
Sale, M
Kuhlenbäumer, G
Doney, ASF
Vicente, AM
Delavaran, H
Algra, A
Davies, G
Oliveira, SA
Palmer, CNA
Deary, I
Schmidt, H
Pandolfo, M
Montaner, J
Carty, C
de Bakker, PIW
Kostulas, K
Ferro, JM
van Zuydam, NR
Valdimarsson, E
Nordestgaard, BG
Lindgren, A
Thijs, V
Slowik, A
Saleheen, D
Paré, G
Berger, K
Thorleifsson, G
Hofman, A
Mosley, TH
Mitchell, BD
Furie, K
Clarke, R
Levi, C
Seshadri, S
Gschwendtner, A
Boncoraglio, GB
Sharma, P
Bis, JC
Gretarsdottir, S
Psaty, BM
Rothwell, PM
Rosand, J
Radiology & Nuclear Medicine
Cardiology
Epidemiology
Source :
The Lancet Neurology, The Lancet Neurology, 11(11), 951-962, Traylor, M, Farrall, M, Holliday, E G, Sudlow, C, Hopewell, J C, Cheng, Y-C, Fornage, M, Ikram, M A, Malik, R, Bevan, S, Thorsteinsdottir, U, Nalls, M A, Longstreth, W, Wiggins, K L, Yadav, S, Parati, E A, Destefano, A L, Worrall, B B, Kittner, S J, Khan, M S, Reiner, A P, Helgadottir, A, Achterberg, S, Fernandez-Cadenas, I, Abboud, S, Schmidt, R, Walters, M, Chen, W-M, Ringelstein, E B, O'Donnell, M, Ho, W K, Pera, J, Lemmens, R, Norrving, B, Higgins, P, Benn, M, Sale, M, Kuhlenbäumer, G, Doney, A S F, Vicente, A M, Delavaran, H, Algra, A, Davies, G, Oliveira, S A, Palmer, C N A, Deary, I, Schmidt, H, Pandolfo, M & Montaner, J & Carty, C 2012, ' Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration) : a meta-analysis of genome-wide association studies ', Lancet Neurology, vol. 11, no. 11, pp. 951-62 . https://doi.org/10.1016/S1474-4422(12)70234-X, Lancet Neurology, 11(11), 951-962. Lancet Publishing Group, The Lancet. Neurology, The Lancet Neurology; Vol 11
Publication Year :
2012
Publisher :
ELSEVIER SCIENCE INC, 2012.

Abstract

Background: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods: We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings: We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10-16) and ZFHX3 (p=2·28×10-8), and for large-vessel stroke at a 9p21 locus (p=3·32×10-5) and HDAC9 (p=2·03×10-12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p

Details

Language :
English
ISSN :
14744422
Database :
OpenAIRE
Journal :
The Lancet Neurology, The Lancet Neurology, 11(11), 951-962, Traylor, M, Farrall, M, Holliday, E G, Sudlow, C, Hopewell, J C, Cheng, Y-C, Fornage, M, Ikram, M A, Malik, R, Bevan, S, Thorsteinsdottir, U, Nalls, M A, Longstreth, W, Wiggins, K L, Yadav, S, Parati, E A, Destefano, A L, Worrall, B B, Kittner, S J, Khan, M S, Reiner, A P, Helgadottir, A, Achterberg, S, Fernandez-Cadenas, I, Abboud, S, Schmidt, R, Walters, M, Chen, W-M, Ringelstein, E B, O'Donnell, M, Ho, W K, Pera, J, Lemmens, R, Norrving, B, Higgins, P, Benn, M, Sale, M, Kuhlenbäumer, G, Doney, A S F, Vicente, A M, Delavaran, H, Algra, A, Davies, G, Oliveira, S A, Palmer, C N A, Deary, I, Schmidt, H, Pandolfo, M & Montaner, J & Carty, C 2012, ' Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration) : a meta-analysis of genome-wide association studies ', Lancet Neurology, vol. 11, no. 11, pp. 951-62 . https://doi.org/10.1016/S1474-4422(12)70234-X, Lancet Neurology, 11(11), 951-962. Lancet Publishing Group, The Lancet. Neurology, The Lancet Neurology; Vol 11
Accession number :
edsair.doi.dedup.....379db6159900ded79d8c403cab3986e0
Full Text :
https://doi.org/10.1016/S1474-4422(12)70234-X