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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 17228naa a2203229 4500 | |
| 001 | oai:gup.ub.gu.se/247952 | |
| 003 | SwePub | |
| 008 | 240528s2016 | |||||||||||000 ||eng| | |
| 009 | oai:lup.lub.lu.se:e5552769-75cc-472f-939b-5f57ef19a3d4 | |
| 024 | 7 | a https://gup.ub.gu.se/publication/2479522 URI |
| 024 | 7 | a https://doi.org/10.1016/S1474-4422(15)00338-52 DOI |
| 024 | 7 | a https://lup.lub.lu.se/record/e5552769-75cc-472f-939b-5f57ef19a3d42 URI |
| 040 | a (SwePub)gud (SwePub)lu | |
| 041 | a eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Pulit, SLu University Medical Center Utrecht4 aut |
| 245 | 1 0 | a Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study. |
| 264 | 1 | c 2016 |
| 520 | a The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaper0 (SwePub)3012 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicine0 (SwePub)3012 hsv//eng |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Medicinsk genetik0 (SwePub)301072 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Medical Genetics0 (SwePub)301072 hsv//eng |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng |
| 653 | a histone deacetylase 9 | |
| 653 | a transcription factor Pitx2 | |
| 653 | a zinc finger protein | |
| 653 | a nerve protein | |
| 653 | a tetraspanin | |
| 653 | a TSPAN2 protein, human | |
| 653 | a Article | |
| 653 | a atherosclerosis | |
| 653 | a brain ischemia | |
| 653 | a cardioembolic stroke | |
| 653 | a disease classification | |
| 653 | a gene locus | |
| 653 | a genetic association | |
| 653 | a human | |
| 653 | a meta analysis | |
| 653 | a phenotype | |
| 653 | a priority journal | |
| 653 | a single nucleotide polymorphism | |
| 653 | a adolescent | |
| 653 | a adult | |
| 653 | a aged | |
| 653 | a case control study | |
| 653 | a cerebrovascular accident | |
| 653 | a classification | |
| 653 | a cohort analysis | |
| 653 | a genetics | |
| 653 | a genome-wide association study | |
| 653 | a middle aged | |
| 653 | a procedures | |
| 653 | a very elderly | |
| 653 | a young adult | |
| 653 | a Adolescent | |
| 653 | a Adult | |
| 653 | a Aged | |
| 653 | a Aged, 80 and over | |
| 653 | a Brain Ischemia | |
| 653 | a Case-Control Studies | |
| 653 | a Cohort Studies | |
| 653 | a Genetic Loci | |
| 653 | a Genome-Wide Association Study | |
| 653 | a Humans | |
| 653 | a Middle Aged | |
| 653 | a Nerve Tissue Proteins | |
| 653 | a Stroke | |
| 653 | a Tetraspanins | |
| 653 | a Young Adult | |
| 700 | 1 | a McArdle, PF4 aut |
| 700 | 1 | a Wong, Q4 aut |
| 700 | 1 | a Malik, R4 aut |
| 700 | 1 | a Gwinn, K4 aut |
| 700 | 1 | a Achterberg, S4 aut |
| 700 | 1 | a Algra, A4 aut |
| 700 | 1 | a Amouyel, P4 aut |
| 700 | 1 | a Anderson, CD4 aut |
| 700 | 1 | a Arnett, DK4 aut |
| 700 | 1 | a Arsava, EM4 aut |
| 700 | 1 | a Attia, J4 aut |
| 700 | 1 | a Ay, H4 aut |
| 700 | 1 | a Tatlisumak, Turgutu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xtatlt |
| 700 | 1 | a Battey, T4 aut |
| 700 | 1 | a Benavente, OR4 aut |
| 700 | 1 | a Bevan, S4 aut |
| 700 | 1 | a Biffi, A4 aut |
| 700 | 1 | a Jern, Christina,d 1962u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology4 aut0 (Swepub:gu)xjerch |
| 700 | 1 | a Blanton, SH4 aut |
| 700 | 1 | a Boncoraglio, GB4 aut |
| 700 | 1 | a Brown Jr, RD4 aut |
| 700 | 1 | a Ilinca, Andreeau Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Klinisk neurogenetik,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Stroke Research Group,Lund University Research Groups,Clinical Neurogenetics,Landskrona Hospital4 aut0 (Swepub:lu)med-ari |
| 700 | 1 | a Carrera, C4 aut |
| 700 | 1 | a Chapman Smith, SN4 aut |
| 700 | 1 | a Chasman, DI4 aut |
| 700 | 1 | a Chauhan, G4 aut |
| 700 | 1 | a Chen, W-M4 aut |
| 700 | 1 | a Cheng, Y-C4 aut |
| 700 | 1 | a Chong, M4 aut |
| 700 | 1 | a Cloonan, LK4 aut |
| 700 | 1 | a Cole, JW4 aut |
| 700 | 1 | a Cotlarciuc, I4 aut |
| 700 | 1 | a Cruchaga, C4 aut |
| 700 | 1 | a Cuadrado-Godia, E4 aut |
| 700 | 1 | a Dave, T4 aut |
| 700 | 1 | a Dawson, J4 aut |
| 700 | 1 | a Debette, S4 aut |
| 700 | 1 | a Delavaran, Hosseinu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-hmh |
| 700 | 1 | a Dell, CA4 aut |
| 700 | 1 | a Dichgans, M4 aut |
| 700 | 1 | a Doheny, KF4 aut |
| 700 | 1 | a Dong, C4 aut |
| 700 | 1 | a Duggan, DJ4 aut |
| 700 | 1 | a Engström, Gunnaru Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)smi-gen |
| 700 | 1 | a Evans, MK4 aut |
| 700 | 1 | a Estivill Pallejà, X4 aut |
| 700 | 1 | a Faul, JD4 aut |
| 700 | 1 | a Fernández-Cadenas, I4 aut |
| 700 | 1 | a Fornage, M4 aut |
| 700 | 1 | a Frossard, PM4 aut |
| 700 | 1 | a Furie, K4 aut |
| 700 | 1 | a Gamble, DM4 aut |
| 700 | 1 | a Gieger, C4 aut |
| 700 | 1 | a Giese, A-K4 aut |
| 700 | 1 | a Giralt-Steinhauer, E4 aut |
| 700 | 1 | a González, HM4 aut |
| 700 | 1 | a Goris, A4 aut |
| 700 | 1 | a Gretarsdottir, S4 aut |
| 700 | 1 | a Redfors, Petrau Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation4 aut0 (Swepub:gu)xredpe |
| 700 | 1 | a Grittner, U4 aut |
| 700 | 1 | a Gustafsson, S4 aut |
| 700 | 1 | a Han, B4 aut |
| 700 | 1 | a Hankey, GJ4 aut |
| 700 | 1 | a Heitsch, L4 aut |
| 700 | 1 | a Higgins, P4 aut |
| 700 | 1 | a Hochberg, MC4 aut |
| 700 | 1 | a Holliday, E4 aut |
| 700 | 1 | a Hopewell, JC4 aut |
| 700 | 1 | a Horenstein, RB4 aut |
| 700 | 1 | a Howard, G4 aut |
| 700 | 1 | a Ikram, MA4 aut |
| 700 | 1 | a Ilinca, A4 aut |
| 700 | 1 | a Ingelsson, E4 aut |
| 700 | 1 | a Irvin, MR4 aut |
| 700 | 1 | a Jackson, RD4 aut |
| 700 | 1 | a Jern, Christina,d 1962u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology4 aut0 (Swepub:gu)xjerch |
| 700 | 1 | a Jiménez Conde, J4 aut |
| 700 | 1 | a Johnson, JA4 aut |
| 700 | 1 | a Jood, Katarina,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation4 aut0 (Swepub:gu)xjooka |
| 700 | 1 | a Söderholm, Martinu Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)med-ms8 |
| 700 | 1 | a Kaplan, R4 aut |
| 700 | 1 | a Kappelle, LJ4 aut |
| 700 | 1 | a Kardia, SLR4 aut |
| 700 | 1 | a Keene, KL4 aut |
| 700 | 1 | a Kissela, BM4 aut |
| 700 | 1 | a Kleindorfer, DO4 aut |
| 700 | 1 | a Koblar, S4 aut |
| 700 | 1 | a Labovitz, D4 aut |
| 700 | 1 | a Launer, LJ4 aut |
| 700 | 1 | a Laurie, CC4 aut |
| 700 | 1 | a Laurie, CA4 aut |
| 700 | 1 | a Hyunkyu Lee, C4 aut |
| 700 | 1 | a Lee, J-M4 aut |
| 700 | 1 | a Lehm, M4 aut |
| 700 | 1 | a Lemmens, R4 aut |
| 700 | 1 | a Levi, C4 aut |
| 700 | 1 | a Leys, D4 aut |
| 700 | 1 | a Lindgren, Arneu Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Klinisk strokeforskning,Forskargrupper vid Lunds universitet,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,Clinical Stroke Research Group,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)neur-ali |
| 700 | 1 | a Longstreth Jr, WT4 aut |
| 700 | 1 | a Maguire, J4 aut |
| 700 | 1 | a Manichaikul, A4 aut |
| 700 | 1 | a Markus, HS4 aut |
| 700 | 1 | a McClure, LA4 aut |
| 700 | 1 | a McDonough, CW4 aut |
| 700 | 1 | a Meisinger, C4 aut |
| 700 | 1 | a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital4 aut0 (Swepub:lu)endo-ome |
| 700 | 1 | a Meschia, JF4 aut |
| 700 | 1 | a Mola-Caminal, M4 aut |
| 700 | 1 | a Montaner, J4 aut |
| 700 | 1 | a Mosley, TH4 aut |
| 700 | 1 | a Müller-Nurasyid, M4 aut |
| 700 | 1 | a Nalls, MA4 aut |
| 700 | 1 | a O’Connell, JR4 aut |
| 700 | 1 | a O’Donnell, M4 aut |
| 700 | 1 | a Ois, Á4 aut |
| 700 | 1 | a Papanicolaou, GJ4 aut |
| 700 | 1 | a Paré, G4 aut |
| 700 | 1 | a Reddy Peddareddygari, L4 aut |
| 700 | 1 | a Pedersen, Annie,d 1981u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics4 aut0 (Swepub:gu)xpeder |
| 700 | 1 | a Pera, J4 aut |
| 700 | 1 | a Peters, A4 aut |
| 700 | 1 | a Poole, D4 aut |
| 700 | 1 | a Psaty, BM4 aut |
| 700 | 1 | a Rabionet, R4 aut |
| 700 | 1 | a Raffeld, MR4 aut |
| 700 | 1 | a Rannikmäe, K4 aut |
| 700 | 1 | a Rasheed, A4 aut |
| 700 | 1 | a Redfors, Petrau Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering,Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation4 aut0 (Swepub:gu)xredpe |
| 700 | 1 | a Reiner, AP4 aut |
| 700 | 1 | a Rexrode, K4 aut |
| 700 | 1 | a Ribasés, M4 aut |
| 700 | 1 | a Rich, SS4 aut |
| 700 | 1 | a Robberecht, W4 aut |
| 700 | 1 | a Rodriguez-Campello, A4 aut |
| 700 | 1 | a Rolfs, A4 aut |
| 700 | 1 | a Roquer, J4 aut |
| 700 | 1 | a Rose, LM4 aut |
| 700 | 1 | a Rosenbaum, D4 aut |
| 700 | 1 | a Rost, NS4 aut |
| 700 | 1 | a Rothwell, PM4 aut |
| 700 | 1 | a Rundek, T4 aut |
| 700 | 1 | a Ryan, KA4 aut |
| 700 | 1 | a Sacco, RL4 aut |
| 700 | 1 | a Sale, MM4 aut |
| 700 | 1 | a Saleheen, D4 aut |
| 700 | 1 | a Salomaa, V4 aut |
| 700 | 1 | a Sánchez-Mora, C4 aut |
| 700 | 1 | a Oliver Schmidt, C4 aut |
| 700 | 1 | a Schmidt, H4 aut |
| 700 | 1 | a Schmidt, R4 aut |
| 700 | 1 | a Schürks, M4 aut |
| 700 | 1 | a Scott, R4 aut |
| 700 | 1 | a Segal, HC4 aut |
| 700 | 1 | a Seiler, S4 aut |
| 700 | 1 | a Seshadri, S4 aut |
| 700 | 1 | a Sharma, P4 aut |
| 700 | 1 | a Shuldiner, AR4 aut |
| 700 | 1 | a Silver, B4 aut |
| 700 | 1 | a Slowik, A4 aut |
| 700 | 1 | a Smith, JA4 aut |
| 700 | 1 | a Söderholm, M4 aut |
| 700 | 1 | a Soriano, C4 aut |
| 700 | 1 | a Sparks, MJ4 aut |
| 700 | 1 | a Stanne, Tara M,d 1979u Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology4 aut0 (Swepub:gu)xmcdta |
| 700 | 1 | a Stefansson, K4 aut |
| 700 | 1 | a Stine, OC4 aut |
| 700 | 1 | a Strauch, K4 aut |
| 700 | 1 | a Sturm, J4 aut |
| 700 | 1 | a Sudlow, CLM4 aut |
| 700 | 1 | a Tajuddin, SM4 aut |
| 700 | 1 | a Talbert, RL4 aut |
| 700 | 1 | a Tatlisumak, Turgutu Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology4 aut0 (Swepub:gu)xtatlt |
| 700 | 1 | a Thijs, V4 aut |
| 700 | 1 | a Thorleifsson, G4 aut |
| 700 | 1 | a Thorsteindottir, U4 aut |
| 700 | 1 | a Tiedt, S4 aut |
| 700 | 1 | a Traylor, M4 aut |
| 700 | 1 | a Trompet, S4 aut |
| 700 | 1 | a Valant, V4 aut |
| 700 | 1 | a Waldenberger, M4 aut |
| 700 | 1 | a Walters, M4 aut |
| 700 | 1 | a Wang, L4 aut |
| 700 | 1 | a Wassertheil-Smoller, S4 aut |
| 700 | 1 | a Weir, DR4 aut |
| 700 | 1 | a Wiggins, KL4 aut |
| 700 | 1 | a Williams, SR4 aut |
| 700 | 1 | a Wloch-Kopec, D4 aut |
| 700 | 1 | a Woo, D4 aut |
| 700 | 1 | a Woodfield, R4 aut |
| 700 | 1 | a Wu, O4 aut |
| 700 | 1 | a Xu, H4 aut |
| 700 | 1 | a Zonderman, AB4 aut |
| 700 | 1 | a Worrall, Bradfordu University of Virginia School of Medicine4 aut |
| 710 | 2 | a University Medical Center Utrechtb Institutionen för neurovetenskap och fysiologi4 org |
| 773 | 0 | t The Lancet. Neurologyg 15:2, s. 174-84q 15:2<174-84x 1474-4465 |
| 856 | 4 | u http://dx.doi.org/10.1016/S1474-4422(15)00338-5y FULLTEXT |
| 856 | 4 8 | u https://gup.ub.gu.se/publication/247952 |
| 856 | 4 8 | u https://doi.org/10.1016/S1474-4422(15)00338-5 |
| 856 | 4 8 | u https://lup.lub.lu.se/record/e5552769-75cc-472f-939b-5f57ef19a3d4 |
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