8 results on '"Hopewell, Jemma C."'
Search Results
2. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke: Role of Monocyte Chemoattractant Protein-1
- Author
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Georgakis, Marios K., Gill, Dipender, Rannikmäe, Kristiina, Traylor, Matthew, Anderson, Christopher D., Lee, Jin-Moo, Kamatani, Yoichiro, Hopewell, Jemma C., Worrall, Bradford B., Bernhagen, Jürgen, Sudlow, Cathie L. M., Malik, Rainer, and Dichgans, Martin
- Published
- 2019
- Full Text
- View/download PDF
3. Role of Monocyte Chemoattractant Protein-1
- Author
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Sudlow, Catherine, Worrall, Bradford B, Bernhagen, Jürgen, Malik, Rainer, Dichgans, Martin, Georgakis, Marios K, Gill, Dipender, Rannikmae, Kristiina, Traylor, Matthew, Anderson, Christopher D., Lee, Jin-Moo, Kamatani, Yoichiro, and Hopewell, Jemma C.
- Abstract
BACKGROUND: Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a two-sample Mendelian randomization (MR) study.METHODS: Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study (GWAS) of 8,293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE GWAS dataset (67,162 cases; 454,450 controls) applying inverse-variance-weighted meta-analysis, weighted-median analysis, MR-Egger regression, and multivariable MR. The UK Biobank cohort was used as an independent validation sample (4,985 cases; 364,434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits using publicly available GWAS data.RESULTS: Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (OR per 1-SD increase: 1.06, 95% CI: 1.02-1.09, p=0.0009), any ischemic stroke (OR: 1.06, 95% CI: 1.02-1.10, p=0.002), large artery stroke (OR: 1.19, 95% CI: 1.09-1.30, p=0.0002) and cardioembolic stroke (OR: 1.14, 95% CI: 1.06-1.23, p=0.0004), but not with small vessel stroke or intracerebral hemorrhage. The results were stable in sensitivity analyses and remained significant after adjustment for cardiovascular risk factors. Analyses in the UK Biobank showed similar associations for available phenotypes (any stroke: OR: 1.08, 95% CI: 0.99-1.17, p=0.09; any ischemic stroke: OR: 1.07, 95% CI: 0.97-1.18, p=0.17). Genetically determined higher MCP-1 levels were further associated with coronary artery disease (OR: 1.04, 95% CI: 1.00-1.08, p=0.04) and myocardial infarction (OR: 1.05, 95% CI: 1.01-1.09, p=0.02), but not with atrial fibrillation. A meta-analysis of observational studies showed higher circulating MCP-1 levels in stroke patients compared to controls.CONCLUSIONS: Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, particularly with large artery stroke and cardioembolic stroke. Whether targeting MCP-1 or its receptors can lower stroke incidence requires further study.
- Published
- 2019
4. Genetically Determined Levels of Circulating Cytokines and Risk of Stroke.
- Author
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Malik, Rainer, Bernhagen, Jürgen, Dichgans, Martin, Georgakis, Marios K., Kamatani, Yoichiro, Hopewell, Jemma C., Worrall, Bradford B., Gill, Dipender, Sudlow, Cathie L. M., Rannikmäe, Kristiina, Traylor, Matthew, Anderson, Christopher D., and Lee, Jin-Moo
- Published
- 2019
- Full Text
- View/download PDF
5. Multiethnic Meta-Analysis of Genome-Wide Association Studies in >100 000 Subjects Identifies 23 Fibrinogen-Associated Loci but No Strong Evidence of a Causal Association Between Circulating Fibrinogen and Cardiovascular Disease
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Sabater-Lleal, Maria, primary, Huang, Jie, additional, Chasman, Daniel, additional, Naitza, Silvia, additional, Dehghan, Abbas, additional, Johnson, Andrew D., additional, Teumer, Alexander, additional, Reiner, Alex P., additional, Folkersen, Lasse, additional, Basu, Saonli, additional, Rudnicka, Alicja R., additional, Trompet, Stella, additional, Mälarstig, Anders, additional, Baumert, Jens, additional, Bis, Joshua C., additional, Guo, Xiuqing, additional, Hottenga, Jouke J., additional, Shin, So-Youn, additional, Lopez, Lorna M., additional, Lahti, Jari, additional, Tanaka, Toshiko, additional, Yanek, Lisa R., additional, Oudot-Mellakh, Tiphaine, additional, Wilson, James F., additional, Navarro, Pau, additional, Huffman, Jennifer E., additional, Zemunik, Tatijana, additional, Redline, Susan, additional, Mehra, Reena, additional, Pulanic, Drazen, additional, Rudan, Igor, additional, Wright, Alan F., additional, Kolcic, Ivana, additional, Polasek, Ozren, additional, Wild, Sarah H., additional, Campbell, Harry, additional, Curb, J. David, additional, Wallace, Robert, additional, Liu, Simin, additional, Eaton, Charles B., additional, Becker, Diane M., additional, Becker, Lewis C., additional, Bandinelli, Stefania, additional, Räikkönen, Katri, additional, Widen, Elisabeth, additional, Palotie, Aarno, additional, Fornage, Myriam, additional, Green, David, additional, Gross, Myron, additional, Davies, Gail, additional, Harris, Sarah E., additional, Liewald, David C., additional, Starr, John M., additional, Williams, Frances M.K., additional, Grant, Peter J., additional, Spector, Timothy D., additional, Strawbridge, Rona J., additional, Silveira, Angela, additional, Sennblad, Bengt, additional, Rivadeneira, Fernando, additional, Uitterlinden, Andre G., additional, Franco, Oscar H., additional, Hofman, Albert, additional, van Dongen, Jenny, additional, Willemsen, Gonneke, additional, Boomsma, Dorret I., additional, Yao, Jie, additional, Swords Jenny, Nancy, additional, Haritunians, Talin, additional, McKnight, Barbara, additional, Lumley, Thomas, additional, Taylor, Kent D., additional, Rotter, Jerome I., additional, Psaty, Bruce M., additional, Peters, Annette, additional, Gieger, Christian, additional, Illig, Thomas, additional, Grotevendt, Anne, additional, Homuth, Georg, additional, Völzke, Henry, additional, Kocher, Thomas, additional, Goel, Anuj, additional, Franzosi, Maria Grazia, additional, Seedorf, Udo, additional, Clarke, Robert, additional, Steri, Maristella, additional, Tarasov, Kirill V., additional, Sanna, Serena, additional, Schlessinger, David, additional, Stott, David J., additional, Sattar, Naveed, additional, Buckley, Brendan M., additional, Rumley, Ann, additional, Lowe, Gordon D., additional, McArdle, Wendy L., additional, Chen, Ming-Huei, additional, Tofler, Geoffrey H., additional, Song, Jaejoon, additional, Boerwinkle, Eric, additional, Folsom, Aaron R., additional, Rose, Lynda M., additional, Franco-Cereceda, Anders, additional, Teichert, Martina, additional, Ikram, M. Arfan, additional, Mosley, Thomas H., additional, Bevan, Steve, additional, Dichgans, Martin, additional, Rothwell, Peter M., additional, Sudlow, Cathie L.M., additional, Hopewell, Jemma C., additional, Chambers, John C., additional, Saleheen, Danish, additional, Kooner, Jaspal S., additional, Danesh, John, additional, Nelson, Christopher P., additional, Erdmann, Jeanette, additional, Reilly, Muredach P., additional, Kathiresan, Sekar, additional, Schunkert, Heribert, additional, Morange, Pierre-Emmanuel, additional, Ferrucci, Luigi, additional, Eriksson, Johan G., additional, Jacobs, David, additional, Deary, Ian J., additional, Soranzo, Nicole, additional, Witteman, Jacqueline C.M., additional, de Geus, Eco J.C., additional, Tracy, Russell P., additional, Hayward, Caroline, additional, Koenig, Wolfgang, additional, Cucca, Francesco, additional, Jukema, J. Wouter, additional, Eriksson, Per, additional, Seshadri, Sudha, additional, Markus, Hugh S., additional, Watkins, Hugh, additional, Samani, Nilesh J., additional, Wallaschofski, Henri, additional, Smith, Nicholas L., additional, Tregouet, David, additional, Ridker, Paul M, additional, Tang, Weihong, additional, Strachan, David P., additional, Hamsten, Anders, additional, and O’Donnell, Christopher J., additional
- Published
- 2013
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6. Lipids and Lipoproteins and Risk of Different Vascular Events in the MRC/BHF Heart Protection Study
- Author
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Parish, Sarah, primary, Offer, Alison, additional, Clarke, Robert, additional, Hopewell, Jemma C., additional, Hill, Michael R., additional, Otvos, James D., additional, Armitage, Jane, additional, and Collins, Rory, additional
- Published
- 2012
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7. Abstract 18256: Importance of Controlling Dietary Intake of Saturated Fat for Prevention of Coronary Heart Disease: Lessons From the Metabolic Ward Studies
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Clarke, Robert, primary and Hopewell, Jemma C, additional
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- 2011
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8. Role of Monocyte Chemoattractant Protein-1
- Author
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Georgakis, Marios K, Gill, Dipender, Sudlow, Cathie L M, Malik, Rainer, Dichgans, Martin, Rannikmäe, Kristiina, Traylor, Matthew, Anderson, Christopher D, Lee, Jin-Moo, Kamatani, Yoichiro, Hopewell, Jemma C, Worrall, Bradford B, and Bernhagen, Jürgen
- Subjects
Mendelian Randomization Analysis ,genetics [Chemokine CCL2] ,Polymorphism, Single Nucleotide ,Risk Assessment ,diagnosis [Stroke] ,Observational Studies as Topic ,Phenotype ,blood [Stroke] ,Risk Factors ,Case-Control Studies ,blood [Chemokine CCL2] ,genetics [Stroke] ,CCL2 protein, human ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Chemokine CCL2 ,Genome-Wide Association Study - Abstract
Cytokines and growth factors have been implicated in the initiation and propagation of vascular disease. Observational studies have shown associations of their circulating levels with stroke. Our objective was to explore whether genetically determined circulating levels of cytokines and growth factors are associated with stroke and its etiologic subtypes by conducting a 2-sample Mendelian randomization (MR) study.Genetic instruments for 41 cytokines and growth factors were obtained from a genome-wide association study of 8293 healthy adults. Their associations with stroke and stroke subtypes were evaluated in the MEGASTROKE genome-wide association study data set (67 162 cases; 454 450 controls) applying inverse variance-weighted meta-analysis, weighted-median analysis, Mendelian randomization-Egger regression, and multivariable Mendelian randomization. The UK Biobank cohort was used as an independent validation sample (4985 cases; 364 434 controls). Genetic instruments for monocyte chemoattractant protein-1 (MCP-1/CCL2) were further tested for association with etiologically related vascular traits by using publicly available genome-wide association study data.Genetic predisposition to higher MCP-1 levels was associated with higher risk of any stroke (odds ratio [OR] per 1 SD increase, 1.06; 95% CI, 1.02-1.09; P=0.0009), any ischemic stroke (OR, 1.06; 95% CI, 1.02-1.10; P=0.002), large-artery stroke (OR, 1.19; 95% CI, 1.09-1.30; P=0.0002), and cardioembolic stroke (OR, 1.14; 95% CI, 1.06-1.23; P=0.0004), but not with small-vessel stroke or intracerebral hemorrhage. The results were stable in sensitivity analyses and remained significant after adjustment for cardiovascular risk factors. Analyses in the UK Biobank showed similar associations for available phenotypes (any stroke: OR, 1.08; 95% CI, 0.99-1.17; P=0.09; any ischemic stroke: OR, 1.07; 95% CI, 0.97-1.18; P=0.17). Genetically determined higher MCP-1 levels were further associated with coronary artery disease (OR, 1.04; 95% CI, 1.00-1.08; P=0.04) and myocardial infarction (OR, 1.05; 95% CI, 1.01-1.09; P=0.02), but not with atrial fibrillation. A meta-analysis of observational studies showed higher circulating MCP-1 levels in patients with stroke in comparison with controls.Genetic predisposition to elevated circulating levels of MCP-1 is associated with higher risk of stroke, in particular with large-artery stroke and cardioembolic stroke. Whether targeting MCP-1 or its receptors can lower stroke incidence requires further study.
- Full Text
- View/download PDF
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