Search

Your search keyword '"Cooke, John P"' showing total 19 results
Start Over Author "Cooke, John P" Publication Type Electronic Resources
19 results on '"Cooke, John P"'

1. Convergences of Life Sciences and Engineering in Understanding and Treating Heart Failure.

Author

Berry, Joel L, Berry, Joel L, Zhu, Wuqiang, Tang, Yao Liang, Krishnamurthy, Prasanna, Ge, Ying, Cooke, John P, Chen, Yabing, Garry, Daniel J, Yang, Huang-Tian, Rajasekaran, Namakkal Soorapan, Koch, Walter J, Li, Song, Domae, Keitaro, Qin, Gangjian, Cheng, Ke, Kamp, Timothy J, Ye, Lei, Hu, Shijun, Ogle, Brenda M, Rogers, Jack M, Abel, E Dale, Davis, Michael E, Prabhu, Sumanth D, Liao, Ronglih, Pu, William T, Wang, Yibin, Ping, Peipei, Bursac, Nenad, Vunjak-Novakovic, Gordana, Wu, Joseph C, Bolli, Roberto, Menasché, Philippe, Zhang, Jianyi, Berry, Joel L, Berry, Joel L, Zhu, Wuqiang, Tang, Yao Liang, Krishnamurthy, Prasanna, Ge, Ying, Cooke, John P, Chen, Yabing, Garry, Daniel J, Yang, Huang-Tian, Rajasekaran, Namakkal Soorapan, Koch, Walter J, Li, Song, Domae, Keitaro, Qin, Gangjian, Cheng, Ke, Kamp, Timothy J, Ye, Lei, Hu, Shijun, Ogle, Brenda M, Rogers, Jack M, Abel, E Dale, Davis, Michael E, Prabhu, Sumanth D, Liao, Ronglih, Pu, William T, Wang, Yibin, Ping, Peipei, Bursac, Nenad, Vunjak-Novakovic, Gordana, Wu, Joseph C, Bolli, Roberto, Menasché, Philippe, and Zhang, Jianyi

Abstract

On March 1 and 2, 2018, the National Institutes of Health 2018 Progenitor Cell Translational Consortium, Cardiovascular Bioengineering Symposium, was held at the University of Alabama at Birmingham. Convergence of life sciences and engineering to advance the understanding and treatment of heart failure was the theme of the meeting. Over 150 attendees were present, and >40 scientists presented their latest work on engineering human functional myocardium for disease modeling, drug development, and heart failure research. The scientists, engineers, and physicians in the field of cardiovascular sciences met and discussed the most recent advances in their work and proposed future strategies for overcoming the major roadblocks of cardiovascular bioengineering and therapy. Particular emphasis was given for manipulation and using of stem/progenitor cells, biomaterials, and methods to provide molecular, chemical, and mechanical cues to cells to influence their identity and fate in vitro and in vivo. Collectively, these works are profoundly impacting and progressing toward deciphering the mechanisms and developing novel treatments for left ventricular dysfunction of failing hearts. Here, we present some important perspectives that emerged from this meeting.

Published
2019

2. AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate.

Author

Gu, Qilin, Gu, Qilin, Yang, Xiaojie, Lv, Jie, Zhang, Jiaxiong, Xia, Bo, Kim, Jun-Dae, Wang, Ruoyu, Xiong, Feng, Meng, Shu, Clements, Thomas P, Tandon, Bhavna, Wagner, Daniel S, Diaz, Miguel F, Wenzel, Pamela L, Miller, Yury I, Traver, David, Cooke, John P, Li, Wenbo, Zon, Leonard I, Chen, Kaifu, Bai, Yongping, Fang, Longhou, Gu, Qilin, Gu, Qilin, Yang, Xiaojie, Lv, Jie, Zhang, Jiaxiong, Xia, Bo, Kim, Jun-Dae, Wang, Ruoyu, Xiong, Feng, Meng, Shu, Clements, Thomas P, Tandon, Bhavna, Wagner, Daniel S, Diaz, Miguel F, Wenzel, Pamela L, Miller, Yury I, Traver, David, Cooke, John P, Li, Wenbo, Zon, Leonard I, Chen, Kaifu, Bai, Yongping, and Fang, Longhou

Abstract

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.

Published
2019

3. Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing mode

Author

Clayton, Zoe E., Tan, Richard P., Miravet, Maria M., Lennartsson, Katarina, Cooke, John P., Bursill, Christina A., Wise, Steven G., Patel, Sanjay, Clayton, Zoe E., Tan, Richard P., Miravet, Maria M., Lennartsson, Katarina, Cooke, John P., Bursill, Christina A., Wise, Steven G., and Patel, Sanjay

Abstract

Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 x 10(5)) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds., Funding Agencies|National Health and Medical Research Council (NHMRC) Early Career Fellowship [GNT0633283]

Published
2018
Full Text
View/download PDF

4. State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization: A Scientific Statement From the American Heart Association.

Author

Simons, Michael, Simons, Michael, Alitalo, Kari, Annex, Brian H, Augustin, Hellmut G, Beam, Craig, Berk, Bradford C, Byzova, Tatiana, Carmeliet, Peter, Chilian, William, Cooke, John P, Davis, George E, Eichmann, Anne, Iruela-Arispe, M Luisa, Keshet, Eli, Sinusas, Albert J, Ruhrberg, Christiana, Woo, Y Joseph, Dimmeler, Stefanie, American Heart Association Council on Basic Cardiovascular Sciences and Council on Cardiovascular Surgery and Anesthesia, Simons, Michael, Simons, Michael, Alitalo, Kari, Annex, Brian H, Augustin, Hellmut G, Beam, Craig, Berk, Bradford C, Byzova, Tatiana, Carmeliet, Peter, Chilian, William, Cooke, John P, Davis, George E, Eichmann, Anne, Iruela-Arispe, M Luisa, Keshet, Eli, Sinusas, Albert J, Ruhrberg, Christiana, Woo, Y Joseph, Dimmeler, Stefanie, and American Heart Association Council on Basic Cardiovascular Sciences and Council on Cardiovascular Surgery and Anesthesia

Published
2015

5. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Author

Shah, Nigam H, Shah, Nigam H, LePendu, Paea, Bauer-Mehren, Anna, Ghebremariam, Yohannes T, Iyer, Srinivasan V, Marcus, Jake, Nead, Kevin T, Cooke, John P, Leeper, Nicholas J, Shah, Nigam H, Shah, Nigam H, LePendu, Paea, Bauer-Mehren, Anna, Ghebremariam, Yohannes T, Iyer, Srinivasan V, Marcus, Jake, Nead, Kevin T, Cooke, John P, and Leeper, Nicholas J

Abstract

Background and aimsProton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.MethodsUsing a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.ResultsIn multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.ConclusionsConsistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

Published
2015

6. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.

Author

Shah, Nigam H, Guo, Yiru1, Shah, Nigam H, LePendu, Paea, Bauer-Mehren, Anna, Ghebremariam, Yohannes T, Iyer, Srinivasan V, Marcus, Jake, Nead, Kevin T, Cooke, John P, Leeper, Nicholas J, Shah, Nigam H, Guo, Yiru1, Shah, Nigam H, LePendu, Paea, Bauer-Mehren, Anna, Ghebremariam, Yohannes T, Iyer, Srinivasan V, Marcus, Jake, Nead, Kevin T, Cooke, John P, and Leeper, Nicholas J

Abstract

Background and aimsProton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.MethodsUsing a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.ResultsIn multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.ConclusionsConsistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.

Published
2015

7. State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization: A Scientific Statement From the American Heart Association.

Author

Simons, Michael, Simons, Michael, Alitalo, Kari, Annex, Brian H, Augustin, Hellmut G, Beam, Craig, Berk, Bradford C, Byzova, Tatiana, Carmeliet, Peter, Chilian, William, Cooke, John P, Davis, George E, Eichmann, Anne, Iruela-Arispe, M Luisa, Keshet, Eli, Sinusas, Albert J, Ruhrberg, Christiana, Woo, Y Joseph, Dimmeler, Stefanie, American Heart Association Council on Basic Cardiovascular Sciences and Council on Cardiovascular Surgery and Anesthesia, Simons, Michael, Simons, Michael, Alitalo, Kari, Annex, Brian H, Augustin, Hellmut G, Beam, Craig, Berk, Bradford C, Byzova, Tatiana, Carmeliet, Peter, Chilian, William, Cooke, John P, Davis, George E, Eichmann, Anne, Iruela-Arispe, M Luisa, Keshet, Eli, Sinusas, Albert J, Ruhrberg, Christiana, Woo, Y Joseph, Dimmeler, Stefanie, and American Heart Association Council on Basic Cardiovascular Sciences and Council on Cardiovascular Surgery and Anesthesia

Published
2015

8. Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.

Author

White, Mark P, White, Mark P, Rufaihah, Abdul J, Liu, Lei, Ghebremariam, Yohannes T, Ivey, Kathryn N, Cooke, John P, Srivastava, Deepak, White, Mark P, White, Mark P, Rufaihah, Abdul J, Liu, Lei, Ghebremariam, Yohannes T, Ivey, Kathryn N, Cooke, John P, and Srivastava, Deepak

Abstract

Recent evidence suggests human embryonic stem cell (hESC) and induced pluripotent stem (iPS) cell lines have differences in their epigenetic marks and transcriptomes, yet the impact of these differences on subsequent terminally differentiated cells is less well understood. Comparison of purified, homogeneous populations of somatic cells derived from multiple independent human iPS and ES lines will be required to address this critical question. Here, we report a differentiation protocol based on embryonic development that consistently yields large numbers of endothelial cells (ECs) derived from multiple hESCs or iPS cells. Mesoderm differentiation of embryoid bodies was maximized, and defined growth factors were used to generate KDR(+) EC progenitors. Magnetic purification of a KDR(+) progenitor subpopulation resulted in an expanding, homogeneous pool of ECs that expressed EC markers and had functional properties of ECs. Comparison of the transcriptomes revealed limited gene expression variability between multiple lines of human iPS-derived ECs or between lines of ES- and iPS-derived ECs. These results demonstrate a method to generate large numbers of pure human EC progenitors and differentiated ECs from pluripotent stem cells and suggest individual lineages derived from human iPS cells may have significantly less variance than their pluripotent founders.

Published
2013

9. Pharmacovigilance using Clinical Text.

Author

Lependu, Paea, Lependu, Paea, Iyer, Srinivasan V, Bauer-Mehren, Anna, Harpaz, Rave, Ghebremariam, Yohannes T, Cooke, John P, Shah, Nigam H, Lependu, Paea, Lependu, Paea, Iyer, Srinivasan V, Bauer-Mehren, Anna, Harpaz, Rave, Ghebremariam, Yohannes T, Cooke, John P, and Shah, Nigam H

Abstract

The current state of the art in post-marketing drug surveillance utilizes voluntarily submitted reports of suspected adverse drug reactions. We present data mining methods that transform unstructured patient notes taken by doctors, nurses and other clinicians into a de-identified, temporally ordered, patient-feature matrix using standardized medical terminologies. We demonstrate how to use the resulting high-throughput data to monitor for adverse drug events based on the clinical notes in the EHR.

Published
2013

10. Limited gene expression variation in human embryonic stem cell and induced pluripotent stem cell-derived endothelial cells.

Author

White, Mark P, White, Mark P, Rufaihah, Abdul J, Liu, Lei, Ghebremariam, Yohannes T, Ivey, Kathryn N, Cooke, John P, Srivastava, Deepak, White, Mark P, White, Mark P, Rufaihah, Abdul J, Liu, Lei, Ghebremariam, Yohannes T, Ivey, Kathryn N, Cooke, John P, and Srivastava, Deepak

Abstract

Recent evidence suggests human embryonic stem cell (hESC) and induced pluripotent stem (iPS) cell lines have differences in their epigenetic marks and transcriptomes, yet the impact of these differences on subsequent terminally differentiated cells is less well understood. Comparison of purified, homogeneous populations of somatic cells derived from multiple independent human iPS and ES lines will be required to address this critical question. Here, we report a differentiation protocol based on embryonic development that consistently yields large numbers of endothelial cells (ECs) derived from multiple hESCs or iPS cells. Mesoderm differentiation of embryoid bodies was maximized, and defined growth factors were used to generate KDR(+) EC progenitors. Magnetic purification of a KDR(+) progenitor subpopulation resulted in an expanding, homogeneous pool of ECs that expressed EC markers and had functional properties of ECs. Comparison of the transcriptomes revealed limited gene expression variability between multiple lines of human iPS-derived ECs or between lines of ES- and iPS-derived ECs. These results demonstrate a method to generate large numbers of pure human EC progenitors and differentiated ECs from pluripotent stem cells and suggest individual lineages derived from human iPS cells may have significantly less variance than their pluripotent founders.

Published
2013

11. Pharmacovigilance using Clinical Text.

Author

Lependu, Paea, Lependu, Paea, Iyer, Srinivasan V, Bauer-Mehren, Anna, Harpaz, Rave, Ghebremariam, Yohannes T, Cooke, John P, Shah, Nigam H, Lependu, Paea, Lependu, Paea, Iyer, Srinivasan V, Bauer-Mehren, Anna, Harpaz, Rave, Ghebremariam, Yohannes T, Cooke, John P, and Shah, Nigam H

Abstract

The current state of the art in post-marketing drug surveillance utilizes voluntarily submitted reports of suspected adverse drug reactions. We present data mining methods that transform unstructured patient notes taken by doctors, nurses and other clinicians into a de-identified, temporally ordered, patient-feature matrix using standardized medical terminologies. We demonstrate how to use the resulting high-throughput data to monitor for adverse drug events based on the clinical notes in the EHR.

Published
2013

12. Conversion of human fibroblasts to functional endothelial cells by defined factors.

Author

Li, Jun, Li, Jun, Huang, Ngan F, Zou, Jun, Laurent, Timothy J, Lee, Jerry C, Okogbaa, Janet, Cooke, John P, Ding, Sheng, Li, Jun, Li, Jun, Huang, Ngan F, Zou, Jun, Laurent, Timothy J, Lee, Jerry C, Okogbaa, Janet, Cooke, John P, and Ding, Sheng

Abstract

ObjectiveTransdifferentiation of fibroblasts to endothelial cells (ECs) may provide a novel therapeutic avenue for diseases, including ischemia and fibrosis. Here, we demonstrate that human fibroblasts can be transdifferentiated into functional ECs by using only 2 factors, Oct4 and Klf4, under inductive signaling conditions.Approach and resultsTo determine whether human fibroblasts could be converted into ECs by transient expression of pluripotency factors, human neonatal fibroblasts were transduced with lentiviruses encoding Oct4 and Klf4 in the presence of soluble factors that promote the induction of an endothelial program. After 28 days, clusters of induced endothelial (iEnd) cells seemed and were isolated for further propagation and subsequent characterization. The iEnd cells resembled primary human ECs in their transcriptional signature by expressing endothelial phenotypic markers, such as CD31, vascular endothelial-cadherin, and von Willebrand Factor. Furthermore, the iEnd cells could incorporate acetylated low-density lipoprotein and form vascular structures in vitro and in vivo. When injected into the ischemic limb of mice, the iEnd cells engrafted, increased capillary density, and enhanced tissue perfusion. During the transdifferentiation process, the endogenous pluripotency network was not activated, suggesting that this process bypassed a pluripotent intermediate step.ConclusionsPluripotent factor-induced transdifferentiation can be successfully applied for generating functional autologous ECs for therapeutic applications.

Published
2013

13. Genetic determinants of the ankle-brachial index:a meta-analysis of a cardiovascular candidate gene 50K SNP panel in the candidate gene association resource (CARe) consortium

Author

Wassel, Christina L, Lamina, Claudia, Nambi, Vijay, Coassin, Stefan, Mukamal, Kenneth J, Ganesh, Santhi K, Jacobs, David R, Franceschini, Nora, Papanicolaou, George J, Gibson, Quince, Yanek, Lisa R, van der Harst, Pim, Ferguson, Jane F, Crawford, Dana C, Waite, Lindsay L, Allison, Matthew A, Criqui, Michael H, McDermott, Mary M, Mehra, Reena, Cupples, L Adrienne, Hwang, Shih-Jen, Redline, Susan, Kaplan, Robert C, Heiss, Gerardo, Rotter, Jerome I, Boerwinkle, Eric, Taylor, Herman A, Eraso, Luis H, Haun, Margot, Li, Mingyao, Meisinger, Christa, O'Connell, Jeffrey R, Shuldiner, Alan R, Tybjærg-Hansen, Anne, Frikke-Schmidt, Ruth, Kollerits, Barbara, Rantner, Barbara, Dieplinger, Benjamin, Stadler, Marietta, Mueller, Thomas, Haltmayer, Meinhard, Klein-Weigel, Peter, Summerer, Monika, Wichmann, H-Erich, Asselbergs, Folkert W, Navis, Gerjan, Leach, Irene Mateo, Brown-Gentry, Kristin, Goodloe, Robert, Assimes, Themistocles L, Becker, Diane M, Cooke, John P, Absher, Devin M, Olin, Jeffrey W, Mitchell, Braxton D, Reilly, Muredach P, Mohler, Emile R, North, Kari E, Reiner, Alexander P, Kronenberg, Florian, Murabito, Joanne M, Wassel, Christina L, Lamina, Claudia, Nambi, Vijay, Coassin, Stefan, Mukamal, Kenneth J, Ganesh, Santhi K, Jacobs, David R, Franceschini, Nora, Papanicolaou, George J, Gibson, Quince, Yanek, Lisa R, van der Harst, Pim, Ferguson, Jane F, Crawford, Dana C, Waite, Lindsay L, Allison, Matthew A, Criqui, Michael H, McDermott, Mary M, Mehra, Reena, Cupples, L Adrienne, Hwang, Shih-Jen, Redline, Susan, Kaplan, Robert C, Heiss, Gerardo, Rotter, Jerome I, Boerwinkle, Eric, Taylor, Herman A, Eraso, Luis H, Haun, Margot, Li, Mingyao, Meisinger, Christa, O'Connell, Jeffrey R, Shuldiner, Alan R, Tybjærg-Hansen, Anne, Frikke-Schmidt, Ruth, Kollerits, Barbara, Rantner, Barbara, Dieplinger, Benjamin, Stadler, Marietta, Mueller, Thomas, Haltmayer, Meinhard, Klein-Weigel, Peter, Summerer, Monika, Wichmann, H-Erich, Asselbergs, Folkert W, Navis, Gerjan, Leach, Irene Mateo, Brown-Gentry, Kristin, Goodloe, Robert, Assimes, Themistocles L, Becker, Diane M, Cooke, John P, Absher, Devin M, Olin, Jeffrey W, Mitchell, Braxton D, Reilly, Muredach P, Mohler, Emile R, North, Kari E, Reiner, Alexander P, Kronenberg, Florian, and Murabito, Joanne M

Abstract

Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ∼50,000 SNPs across ∼2100 candidate genes to identify genetic variants for ABI.

Published
2012

14. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Author

Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, Kronenberg, Florian, Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, and Kronenberg, Florian

Abstract

BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. METHODS AND RESULTS: -Continuous ABI and PAD (ABI=0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (ß= -0.006, p=2.46x10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI: DAB21P (rs13290547, p=3.6x10(-5)); CYBA (rs3794624, p=6.3x10(-5)); and rs1122608 (LDLR, p=0.0026). CONCLUSIONS: -GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI.

Published
2012

15. Genetic determinants of the ankle-brachial index:a meta-analysis of a cardiovascular candidate gene 50K SNP panel in the candidate gene association resource (CARe) consortium

Author

Wassel, Christina L, Lamina, Claudia, Nambi, Vijay, Coassin, Stefan, Mukamal, Kenneth J, Ganesh, Santhi K, Jacobs, David R, Franceschini, Nora, Papanicolaou, George J, Gibson, Quince, Yanek, Lisa R, van der Harst, Pim, Ferguson, Jane F, Crawford, Dana C, Waite, Lindsay L, Allison, Matthew A, Criqui, Michael H, McDermott, Mary M, Mehra, Reena, Cupples, L Adrienne, Hwang, Shih-Jen, Redline, Susan, Kaplan, Robert C, Heiss, Gerardo, Rotter, Jerome I, Boerwinkle, Eric, Taylor, Herman A, Eraso, Luis H, Haun, Margot, Li, Mingyao, Meisinger, Christa, O'Connell, Jeffrey R, Shuldiner, Alan R, Tybjærg-Hansen, Anne, Frikke-Schmidt, Ruth, Kollerits, Barbara, Rantner, Barbara, Dieplinger, Benjamin, Stadler, Marietta, Mueller, Thomas, Haltmayer, Meinhard, Klein-Weigel, Peter, Summerer, Monika, Wichmann, H-Erich, Asselbergs, Folkert W, Navis, Gerjan, Leach, Irene Mateo, Brown-Gentry, Kristin, Goodloe, Robert, Assimes, Themistocles L, Becker, Diane M, Cooke, John P, Absher, Devin M, Olin, Jeffrey W, Mitchell, Braxton D, Reilly, Muredach P, Mohler, Emile R, North, Kari E, Reiner, Alexander P, Kronenberg, Florian, Murabito, Joanne M, Wassel, Christina L, Lamina, Claudia, Nambi, Vijay, Coassin, Stefan, Mukamal, Kenneth J, Ganesh, Santhi K, Jacobs, David R, Franceschini, Nora, Papanicolaou, George J, Gibson, Quince, Yanek, Lisa R, van der Harst, Pim, Ferguson, Jane F, Crawford, Dana C, Waite, Lindsay L, Allison, Matthew A, Criqui, Michael H, McDermott, Mary M, Mehra, Reena, Cupples, L Adrienne, Hwang, Shih-Jen, Redline, Susan, Kaplan, Robert C, Heiss, Gerardo, Rotter, Jerome I, Boerwinkle, Eric, Taylor, Herman A, Eraso, Luis H, Haun, Margot, Li, Mingyao, Meisinger, Christa, O'Connell, Jeffrey R, Shuldiner, Alan R, Tybjærg-Hansen, Anne, Frikke-Schmidt, Ruth, Kollerits, Barbara, Rantner, Barbara, Dieplinger, Benjamin, Stadler, Marietta, Mueller, Thomas, Haltmayer, Meinhard, Klein-Weigel, Peter, Summerer, Monika, Wichmann, H-Erich, Asselbergs, Folkert W, Navis, Gerjan, Leach, Irene Mateo, Brown-Gentry, Kristin, Goodloe, Robert, Assimes, Themistocles L, Becker, Diane M, Cooke, John P, Absher, Devin M, Olin, Jeffrey W, Mitchell, Braxton D, Reilly, Muredach P, Mohler, Emile R, North, Kari E, Reiner, Alexander P, Kronenberg, Florian, and Murabito, Joanne M

Abstract

Candidate gene association studies for peripheral artery disease (PAD), including subclinical disease assessed with the ankle-brachial index (ABI), have been limited by the modest number of genes examined. We conducted a two stage meta-analysis of ∼50,000 SNPs across ∼2100 candidate genes to identify genetic variants for ABI.

Published
2012

16. Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Author

Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, Kronenberg, Florian, Murabito, Joanne M, White, Charles C, Kavousi, Maryam, Sun, Hong Yan, Feitosa, Mary F, Nambi, Vijay, Lamina, Claudia, Schillert, Arne, Coassin, Stefan, Bis, Joshua C, Broer, Linda, Crawford, Dana C, Franceschini, Nora, Frikke-Schmidt, Ruth, Haun, Margot, Holewijn, Suzanne, Huffman, Jennifer E, Hwang, Shih-Jen, Kiechl, Stefan, Kollerits, Barbara, Montasser, May E, Nolte, Ilja M, Rudock, Megan E, Senft, Andrea, Teumer, Alexander, van der Harst, Pim, Vitart, Veronique, Waite, Lindsay L, Wood, Andrew R, Wassel, Christina L, Absher, Devin M, Allison, Matthew A, Amin, Najaf, Arnold, Alice, Asselbergs, Folkert W, Aulchenko, Yurii, Bandinelli, Stefania, Barbalic, Maja, Boban, Mladen, Brown-Gentry, Kristin, Couper, David J, Criqui, Michael H, Dehghan, Abbas, den Heijer, Martin, Dieplinger, Benjamin, Ding, Jingzhong, Dörr, Marcus, Espinola-Klein, Christine, Felix, Stephan B, Ferrucci, Luigi, Folsom, Aaron R, Fraedrich, Gustav, Gibson, Quince, Goodloe, Robert, Gunjaca, Grgo, Haltmayer, Meinhard, Heiss, Gerardo, Hofman, Albert, Kieback, Arne, Kiemeney, Lambertus A, Kolcic, Ivana, Kullo, Iftikhar J, Kritchevsky, Stephen B, Lackner, Karl J, Li, Xiaohui, Lieb, Wolfgang, Lohman, Kurt, Meisinger, Christa, Melzer, David, Mohler, Emile R, Mudnic, Ivana, Mueller, Thomas, Navis, Gerjan, Oberhollenzer, Friedrich, Olin, Jeffrey W, O'Connell, Jeff, O'Donnell, Christopher J, Palmas, Walter, Penninx, Brenda W, Petersmann, Astrid, Polasek, Ozren, Psaty, Bruce M, Rantner, Barbara, Rice, Ken, Rivadeneira, Fernando, Rotter, Jerome I, Seldenrijk, Adrie, Stadler, Marietta, Summerer, Monika, Tanaka, Toshiko, Tybjærg-Hansen, Anne, Uitterlinden, Andre G, van Gilst, Wiek H, Vermeulen, Sita H, Wild, Sarah H, Wild, Philipp S, Willeit, Johann, Zeller, Tanja, Zemunik, Tatijana, Zgaga, Lina, Assimes, Themistocles L, Blankenberg, Stefan, Boerwinkle, Eric, Campbell, Harry, Cooke, John P, de Graaf, Jaqueline, Herrington, David, Kardia, Sharon L R, Mitchell, Braxton D, Murray, Anna, Münzel, Thomas, Newman, Anne, Oostra, Ben A, Rudan, Igor, Shuldiner, Alan R, Snieder, Harold, van Duijn, Cornelia M, Völker, Uwe, Wright, Alan F, Wichmann, H-Erich, Wilson, James, Witteman, Jacqueline C M, Liu, Yongmei, Hayward, Caroline, Borecki, Ingrid B, Ziegler, Andreas, North, Kari E, Cupples, L Adrienne, and Kronenberg, Florian

Abstract

BACKGROUND: -Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. METHODS AND RESULTS: -Continuous ABI and PAD (ABI=0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ~2.5 million SNPs in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed-effects inverse variance weighted meta-analyses. There were a total of 41,692 participants of European ancestry (~60% women, mean ABI 1.02 to 1.19), including 3,409 participants with PAD and with GWAS data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (ß= -0.006, p=2.46x10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16,717). The association for rs10757269 strengthened in the combined discovery and replication analysis (p=2.65x10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, two previously reported candidate genes for PAD and one SNP associated with coronary artery disease (CAD) were associated with ABI: DAB21P (rs13290547, p=3.6x10(-5)); CYBA (rs3794624, p=6.3x10(-5)); and rs1122608 (LDLR, p=0.0026). CONCLUSIONS: -GWAS in more than 40,000 individuals identified one genome-wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for CAD are associated with ABI.

Published
2012

17. Pat Malloy

Author

Boucicault, Dion, 1820-1890 (Lyricist), Bryant, Dan, 1833-1875 (Performer), Cooke, John P., 1820-1865. (Composer), Boucicault, Dion, 1820-1890 (Lyricist), Bryant, Dan, 1833-1875 (Performer), and Cooke, John P., 1820-1865. (Composer)

18. Pat Malloy

Author

Boucicault, Dion, 1820-1890 (Lyricist), Bryant, Dan, 1833-1875 (Performer), Cooke, John P., 1820-1865. (Composer), Boucicault, Dion, 1820-1890 (Lyricist), Bryant, Dan, 1833-1875 (Performer), and Cooke, John P., 1820-1865. (Composer)

19. Pat Malloy

Author

Boucicault, Dion, 1820-1890, lyricist.; Cooke, John P., 1820-1865, arranger of music.; Drew, Frank, 1831- dedicatee.; Pond, William A., publisher.; Clayten, engraver., Major & Knapp Engraving, Manufacturing & Lithographic Co., lithographer., Boucicault, Dion, 1820-1890, lyricist.; Cooke, John P., 1820-1865, arranger of music.; Drew, Frank, 1831- dedicatee.; Pond, William A., publisher.; Clayten, engraver., and Major & Knapp Engraving, Manufacturing & Lithographic Co., lithographer.

Abstract

Subject:Full-length portrait of Dan Bryant as Pat Malloy seated on a wooden chest, his right foot resting on his right knee, a hat held in his left hand and a haggard expression on his face., Sheet music can be digitized upon request. Title continues: Originally sung with immense success by Mr.Dan Bryant in his inimitable character of the Irish Emigrant at Wallack's Theatre. Words by Dion Bourcicault. Arranged by John P.Cook. To Frank Drew Esq. Plate no.6039. Music engraved at Clayten's. In the Harvard Catalogue of Engraved Dramatic Portraits, Bourcicault is listed as Boucicault., Print fund. November 1985. #1985.05.

Catalog

Books, media, physical & digital resources
See catalog results