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278 results on '"Ruusalepp, Arno"'

1. PERSUADE Survey—PERioperative AnestheSia and Intensive Care Management of Left VentricUlar Assist DevicE Implantation in Europe and the United States

Author

Alfirevic, Andrej, Anton, James M., Antoniou, Theofani, Auci, Elisabetta, Badakhsh, Orode, Banks, Dalia A., Barrio, Jose M., Bartels, Karsten, Belli, Erol V., Bermede, Onat, Bettex, Dominique, Biedermann, Sébastien, Boelsen, Jonas, Boisen, Michael L., Book, Malte, Bottiger, Brandi A., Bouchez, Stefaan, Bräuer, Anselm, Brodt, Jessica L, Chaudhry, Sunit-Preet, Conlin, Frederick T., Cormican, Daniel S., Cristinar, Mircea, Curtis, Michael S., Dalia, Adam A., D'Avino, Emilio, Durand, Michel, Eberle, Balthasar, Emmert, Daniel A., Erb, Joachim M., Falterman, Jason, Forner, Anna Flo, Gatha, Nehal M., Gaudard, Philippe, Giebler, Antasia, Gliga, Louise A., Guarracino, Fabio, Gürcü, Mustafa E., Hans, Gregory A., Hanson, Ross S., Heringlake, Matthias, Hilberath, Jan N., Hommel, Matthias, Huhn, Ragnar, Iyer, Manoj H., Jacquet, Luc M., Karadeniz, Ümit, Kertai, Miklos D., Martin, Archer Kilbourne, Kolarczyk, Lavinia M., Koller, Tobias, Kurian, Dinesh J., Kornfield, Zev N., Koster, Andreas, Kranke, Peter, Krauss, Bernadette, Kudsioglu, Turkan, Kwak, Jenny, Lachauer, Steffen, Lagier, David, Lango, Romuald, Liang, Hong, Lilie, Craig J., Logeman, Elisabeth Angelique, Magunia, Harry, Mahmoud, Saifeldin, Makar, Moody, Markovic, Dejan, Mathis, Michael R., Mattei, Mathieu, Mazzeffi, Michael A., McCabe, Melissa D., Meers, J. Brad, Moitra, Vivek K., Møller-Sørensen, Hasse, Moravcova, Sarka, Muellejans, Bernd, Münch, Christopher M., Murray, Andrew W., Moncho, Azucena Pajares, Ngai, Jennie, Nielsen, Dorthe V., Ortoleva, Jamel P., Ouattara, Alexandre, Patel, Bhoumesh, Paul, Frank, Peng, Yong G., Pittarello, Demetrio, Prabhu, Mahesh, Rancati, Valentina, Rex, Steffen, Riha, Hynek, Robitaille, Mark J., Blanco, Yiliam Rodriguez, Rovira, Irene, Ruusalepp, Arno, Samalavicius, Robertas, Saatee, Siavosh, Sauer, William J., Scheiermann, Patrick, Schlesinger, Rachel E., Schroeder, Andrew M., Schroeder, Sarah E., Shih, Henry, Slaughter, Mark S., Sostaric, Maja, Šribar, Andrej, Svalebjørg, Morten, Székely, Andrea, Szentgyorgyi, Lajos, ter Horst, Maarten, Tschernko, Edda M., Twite, Mark, Ulrichs, Christoph, van der Maaten, Joost M.A.A., van der Ploeg, Nathalie, Vilela, Hugo P., von Homeyer, Peter, Wagner, Nana-Maria, Weiner, Menachem M., Wunder, Christian, Zink, Wolfgang, Kummerow, Maren, von Dossow, Vera, Pasero, Daniela, Martinez Lopez de Arroyabe, Blanca, Abrams, Benjamin, Kowalsky, Markus, Wilkey, Barbara J., Subramanian, Kathirvel, Martin, Archer K., Marczin, Nandor, and de Waal, Eric E.C.

Published
2024
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2. Transcription Factor MAFF (MAF Basic Leucine Zipper Transcription Factor F) Regulates an Atherosclerosis Relevant Network Connecting Inflammation and Cholesterol Metabolism

Author

von Scheidt, Moritz, Zhao, Yuqi, de Aguiar Vallim, Thomas Q, Che, Nam, Wierer, Michael, Seldin, Marcus M, Franzén, Oscar, Kurt, Zeyneb, Pang, Shichao, Bongiovanni, Dario, Yamamoto, Masayuki, Edwards, Peter A, Ruusalepp, Arno, Kovacic, Jason C, Mann, Matthias, Björkegren, Johan LM, Lusis, Aldons J, Yang, Xia, and Schunkert, Heribert

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Health Sciences, Clinical Sciences, Sports Science and Exercise, Cardiovascular, Aging, Biotechnology, Heart Disease, Atherosclerosis, Heart Disease - Coronary Heart Disease, Human Genome, Genetics, Digestive Diseases, 2.1 Biological and endogenous factors, Animals, Cholesterol, DNA-Binding Proteins, Disease Models, Animal, Humans, Inflammation, MafF Transcription Factor, Male, Mice, Mice, Knockout, Nuclear Proteins, atherosclerosis, chromatin immunoprecipitation, coronary artery disease, inflammation, lipopolysaccharides, mafF transcription factor, receptors, LDL, receptors, LDL, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundCoronary artery disease (CAD) is a multifactorial condition with both genetic and exogenous causes. The contribution of tissue-specific functional networks to the development of atherosclerosis remains largely unclear. The aim of this study was to identify and characterize central regulators and networks leading to atherosclerosis.MethodsBased on several hundred genes known to affect atherosclerosis risk in mouse (as demonstrated in knockout models) and human (as shown by genome-wide association studies), liver gene regulatory networks were modeled. The hierarchical order and regulatory directions of genes within the network were based on Bayesian prediction models, as well as experimental studies including chromatin immunoprecipitation DNA-sequencing, chromatin immunoprecipitation mass spectrometry, overexpression, small interfering RNA knockdown in mouse and human liver cells, and knockout mouse experiments. Bioinformatics and correlation analyses were used to clarify associations between central genes and CAD phenotypes in both human and mouse.ResultsThe transcription factor MAFF (MAF basic leucine zipper transcription factor F) interacted as a key driver of a liver network with 3 human genes at CAD genome-wide association studies loci and 11 atherosclerotic murine genes. Most importantly, expression levels of the low-density lipoprotein receptor (LDLR) gene correlated with MAFF in 600 CAD patients undergoing bypass surgery (STARNET [Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task]) and a hybrid mouse diversity panel involving 105 different inbred mouse strains. Molecular mechanisms of MAFF were tested in noninflammatory conditions and showed positive correlation between MAFF and LDLR in vitro and in vivo. Interestingly, after lipopolysaccharide stimulation (inflammatory conditions), an inverse correlation between MAFF and LDLR in vitro and in vivo was observed. Chromatin immunoprecipitation mass spectrometry revealed that the human CAD genome-wide association studies candidate BACH1 (BTB domain and CNC homolog 1) assists MAFF in the presence of lipopolysaccharide stimulation with respective heterodimers binding at the MAF recognition element of the LDLR promoter to transcriptionally downregulate LDLR expression.ConclusionsThe transcription factor MAFF was identified as a novel central regulator of an atherosclerosis/CAD-relevant liver network. MAFF triggered context-specific expression of LDLR and other genes known to affect CAD risk. Our results suggest that MAFF is a missing link between inflammation, lipid and lipoprotein metabolism, and a possible treatment target.

Published
2021

3. Integration of transcriptomes of senescent cell models with multi-tissue patient samples reveals reduced COL6A3 as an inducer of senescence

Author

Savić, Radoslav, Yang, Jialiang, Koplev, Simon, An, Mahru C., Patel, Priyanka L., O’Brien, Robert N., Dubose, Brittany N., Dodatko, Tetyana, Rogatsky, Eduard, Sukhavasi, Katyayani, Ermel, Raili, Ruusalepp, Arno, Houten, Sander M., Kovacic, Jason C., Stewart, Andrew F., Yohn, Christopher B., Schadt, Eric E., Laberge, Remi-Martin, Björkegren, Johan L.M., Tu, Zhidong, and Argmann, Carmen

Published
2023
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4. Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

Author

Kleeman, Sam O., Thakir, Tuba Mansoor, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef J.R.A., Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Sinha, Sarthak, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz G.N., Biernaskie, Jeff, Dufour, Antoine, Tober-Lau, Pinkus, Ruusalepp, Arno, Bjorkegren, Johan L.M., Ralser, Markus, Kurth, Florian, Demichev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H., Walker, Brian R., Meyer, Hannah V., and Janowitz, Tobias

Published
2023
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5. An integrative multiomic network model links lipid metabolism to glucose regulation in coronary artery disease.

Author

Cohain, Ariella, Barrington, William, Jordan, Daniel, Beckmann, Noam, Argmann, Carmen, Houten, Sander, Charney, Alexander, Ermel, Raili, Sukhavasi, Katyayani, Franzen, Oscar, Koplev, Simon, Whatling, Carl, Belbin, Gillian, Yang, Jialiang, Hao, Ke, Kenny, Eimear, Tu, Zhidong, Zhu, Jun, Gan, Li-Ming, Do, Ron, Giannarelli, Chiara, Kovacic, Jason, Ruusalepp, Arno, Lusis, Aldons, Bjorkegren, Johan, and Schadt, Eric

Subjects
Animals, Blood Glucose, Cholesterol, Coronary Artery Disease, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose, Humans, Hypercholesterolemia, Lipid Metabolism, Mice, Inbred C57BL, Models, Biological, Polymorphism, Single Nucleotide, Mice
Abstract

Elevated plasma cholesterol and type 2 diabetes (T2D) are associated with coronary artery disease (CAD). Individuals treated with cholesterol-lowering statins have increased T2D risk, while individuals with hypercholesterolemia have reduced T2D risk. We explore the relationship between lipid and glucose control by constructing network models from the STARNET study with sequencing data from seven cardiometabolic tissues obtained from CAD patients during coronary artery by-pass grafting surgery. By integrating gene expression, genotype, metabolomic, and clinical data, we identify a glucose and lipid determining (GLD) regulatory network showing inverse relationships with lipid and glucose traits. Master regulators of the GLD network also impact lipid and glucose levels in inverse directions. Experimental inhibition of one of the GLD network master regulators, lanosterol synthase (LSS), in mice confirms the inverse relationships to glucose and lipid levels as predicted by our model and provides mechanistic insights.

Published
2021

6. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants

Author

Aragam, Krishna G., Jiang, Tao, Goel, Anuj, Kanoni, Stavroula, Wolford, Brooke N., Atri, Deepak S., Weeks, Elle M., Wang, Minxian, Hindy, George, Zhou, Wei, Grace, Christopher, Roselli, Carolina, Marston, Nicholas A., Kamanu, Frederick K., Surakka, Ida, Venegas, Loreto Muñoz, Sherliker, Paul, Koyama, Satoshi, Ishigaki, Kazuyoshi, Åsvold, Bjørn O., Brown, Michael R., Brumpton, Ben, de Vries, Paul S., Giannakopoulou, Olga, Giardoglou, Panagiota, Gudbjartsson, Daniel F., Güldener, Ulrich, Haider, Syed M. Ijlal, Helgadottir, Anna, Ibrahim, Maysson, Kastrati, Adnan, Kessler, Thorsten, Kyriakou, Theodosios, Konopka, Tomasz, Li, Ling, Ma, Lijiang, Meitinger, Thomas, Mucha, Sören, Munz, Matthias, Murgia, Federico, Nielsen, Jonas B., Nöthen, Markus M., Pang, Shichao, Reinberger, Tobias, Schnitzler, Gavin, Smedley, Damian, Thorleifsson, Gudmar, von Scheidt, Moritz, Ulirsch, Jacob C., Arnar, David O., Burtt, Noël P., Costanzo, Maria C., Flannick, Jason, Ito, Kaoru, Jang, Dong-Keun, Kamatani, Yoichiro, Khera, Amit V., Komuro, Issei, Kullo, Iftikhar J., Lotta, Luca A., Nelson, Christopher P., Roberts, Robert, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Webb, Thomas R., Baras, Aris, Björkegren, Johan L. M., Boerwinkle, Eric, Dedoussis, George, Holm, Hilma, Hveem, Kristian, Melander, Olle, Morrison, Alanna C., Orho-Melander, Marju, Rallidis, Loukianos S., Ruusalepp, Arno, Sabatine, Marc S., Stefansson, Kari, Zalloua, Pierre, Ellinor, Patrick T., Farrall, Martin, Danesh, John, Ruff, Christian T., Finucane, Hilary K., Hopewell, Jemma C., Clarke, Robert, Gupta, Rajat M., Erdmann, Jeanette, Samani, Nilesh J., Schunkert, Heribert, Watkins, Hugh, Willer, Cristen J., Deloukas, Panos, Kathiresan, Sekar, and Butterworth, Adam S.

Published
2022
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7. Opportunities and challenges for transcriptome-wide association studies

Author

Wainberg, Michael, Sinnott-Armstrong, Nasa, Mancuso, Nicholas, Barbeira, Alvaro N, Knowles, David A, Golan, David, Ermel, Raili, Ruusalepp, Arno, Quertermous, Thomas, Hao, Ke, Björkegren, Johan LM, Im, Hae Kyung, Pasaniuc, Bogdan, Rivas, Manuel A, and Kundaje, Anshul

Subjects
Genetics, Human Genome, Prevention, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Crohn Disease, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Lipoproteins, LDL, Quantitative Trait Loci, Schizophrenia, Transcriptome, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Transcriptome-wide association studies (TWAS) integrate genome-wide association studies (GWAS) and gene expression datasets to identify gene-trait associations. In this Perspective, we explore properties of TWAS as a potential approach to prioritize causal genes at GWAS loci, by using simulations and case studies of literature-curated candidate causal genes for schizophrenia, low-density-lipoprotein cholesterol and Crohn's disease. We explore risk loci where TWAS accurately prioritizes the likely causal gene as well as loci where TWAS prioritizes multiple genes, some likely to be non-causal, owing to sharing of expression quantitative trait loci (eQTL). TWAS is especially prone to spurious prioritization with expression data from non-trait-related tissues or cell types, owing to substantial cross-cell-type variation in expression levels and eQTL strengths. Nonetheless, TWAS prioritizes candidate causal genes more accurately than simple baselines. We suggest best practices for causal-gene prioritization with TWAS and discuss future opportunities for improvement. Our results showcase the strengths and limitations of using eQTL datasets to determine causal genes at GWAS loci.

Published
2019

8. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Author

Franceschini, Nora, Giambartolomei, Claudia, de Vries, Paul S, Finan, Chris, Bis, Joshua C, Huntley, Rachael P, Lovering, Ruth C, Tajuddin, Salman M, Winkler, Thomas W, Graff, Misa, Kavousi, Maryam, Dale, Caroline, Smith, Albert V, Hofer, Edith, van Leeuwen, Elisabeth M, Nolte, Ilja M, Lu, Lingyi, Scholz, Markus, Sargurupremraj, Muralidharan, Pitkänen, Niina, Franzén, Oscar, Joshi, Peter K, Noordam, Raymond, Marioni, Riccardo E, Hwang, Shih-Jen, Musani, Solomon K, Schminke, Ulf, Palmas, Walter, Isaacs, Aaron, Correa, Adolfo, Zonderman, Alan B, Hofman, Albert, Teumer, Alexander, Cox, Amanda J, Uitterlinden, André G, Wong, Andrew, Smit, Andries J, Newman, Anne B, Britton, Annie, Ruusalepp, Arno, Sennblad, Bengt, Hedblad, Bo, Pasaniuc, Bogdan, Penninx, Brenda W, Langefeld, Carl D, Wassel, Christina L, Tzourio, Christophe, Fava, Cristiano, Baldassarre, Damiano, O'Leary, Daniel H, Teupser, Daniel, Kuh, Diana, Tremoli, Elena, Mannarino, Elmo, Grossi, Enzo, Boerwinkle, Eric, Schadt, Eric E, Ingelsson, Erik, Veglia, Fabrizio, Rivadeneira, Fernando, Beutner, Frank, Chauhan, Ganesh, Heiss, Gerardo, Snieder, Harold, Campbell, Harry, Völzke, Henry, Markus, Hugh S, Deary, Ian J, Jukema, J Wouter, de Graaf, Jacqueline, Price, Jacqueline, Pott, Janne, Hopewell, Jemma C, Liang, Jingjing, Thiery, Joachim, Engmann, Jorgen, Gertow, Karl, Rice, Kenneth, Taylor, Kent D, Dhana, Klodian, Kiemeney, Lambertus ALM, Lind, Lars, Raffield, Laura M, Launer, Lenore J, Holdt, Lesca M, Dörr, Marcus, Dichgans, Martin, Traylor, Matthew, Sitzer, Matthias, Kumari, Meena, Kivimaki, Mika, Nalls, Mike A, Melander, Olle, Raitakari, Olli, Franco, Oscar H, Rueda-Ochoa, Oscar L, Roussos, Panos, Whincup, Peter H, Amouyel, Philippe, and Giral, Philippe

Subjects
MEGASTROKE Consortium, Humans, Coronary Disease, Genetic Predisposition to Disease, Amino Acid Oxidoreductases, Protein-Lysine 6-Oxidase, Risk Factors, Lod Score, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, Plaque, Atherosclerotic, Carotid Intima-Media Thickness, ADAMTS9 Protein, Plaque, Atherosclerotic, Polymorphism, Single Nucleotide
Abstract

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

Published
2018

9. Publisher Correction: Transcriptome-wide association study of coronary artery disease identifies novel susceptibility genes

Author

Li, Ling, Chen, Zhifen, von Scheidt, Moritz, Li, Shuangyue, Steiner, Andrea, Güldener, Ulrich, Koplev, Simon, Ma, Angela, Hao, Ke, Pan, Calvin, Lusis, Aldons J., Pang, Shichao, Kessler, Thorsten, Ermel, Raili, Sukhavasi, Katyayani, Ruusalepp, Arno, Gagneur, Julien, Erdmann, Jeanette, Kovacic, Jason C., Björkegren, Johan L. M., and Schunkert, Heribert

Published
2022
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10. Transcriptome-wide association study of coronary artery disease identifies novel susceptibility genes

Author

Li, Ling, Chen, Zhifen, von Scheidt, Moritz, Li, Shuangyue, Steiner, Andrea, Güldener, Ulrich, Koplev, Simon, Ma, Angela, Hao, Ke, Pan, Calvin, Lusis, Aldons J., Pang, Shichao, Kessler, Thorsten, Ermel, Raili, Sukhavasi, Katyayani, Ruusalepp, Arno, Gagneur, Julien, Erdmann, Jeanette, Kovacic, Jason C., Björkegren, Johan L. M., and Schunkert, Heribert

Published
2022
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11. A mechanistic framework for cardiometabolic and coronary artery diseases

Author

Koplev, Simon, Seldin, Marcus, Sukhavasi, Katyayani, Ermel, Raili, Pang, Shichao, Zeng, Lingyao, Bankier, Sean, Di Narzo, Antonio, Cheng, Haoxiang, Meda, Vamsidhar, Ma, Angela, Talukdar, Husain, Cohain, Ariella, Amadori, Letizia, Argmann, Carmen, Houten, Sander M., Franzén, Oscar, Mocci, Giuseppe, Meelu, Omar A., Ishikawa, Kiyotake, Whatling, Carl, Jain, Anamika, Jain, Rajeev Kumar, Gan, Li-Ming, Giannarelli, Chiara, Roussos, Panos, Hao, Ke, Schunkert, Heribert, Michoel, Tom, Ruusalepp, Arno, Schadt, Eric E., Kovacic, Jason C., Lusis, Aldon J., and Björkegren, Johan L. M.

Published
2022
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12. Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade

Author

Wang, Ying, Nanda, Vivek, Direnzo, Daniel, Ye, Jianqin, Xiao, Sophia, Kojima, Yoko, Howe, Kathryn L., Jarr, Kai-Uwe, Flores, Alyssa M., Tsantilas, Pavlos, Tsao, Noah, Rao, Abhiram, Newmane, Alexandra A. C., Eberhard, Anne V., Priest, James R., Ruusalepp, Arno, Pasterkamp, Gerard, Maegdefessel, Lars, Miller, Clint L., Lind, Lars, Koplev, Simon, Björkegren, Johan L. M., Owense, Gary K., Ingelsson, Erik, Weissmanr, Irving L., and Leeper, Nicholas J.

Published
2020

13. Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

Author

Crawford, Andrew A., Bankier, Sean, Altmaier, Elisabeth, Barnes, Catriona L. K., Clark, David W., Ermel, Raili, Friedrich, Nele, van der Harst, Pim, Joshi, Peter K., Karhunen, Ville, Lahti, Jari, Mahajan, Anubha, Mangino, Massimo, Nethander, Maria, Neumann, Alexander, Pietzner, Maik, Sukhavasi, Katyayani, Wang, Carol A., Bakker, Stephan J. L., Bjorkegren, Johan L. M., Campbell, Harry, Eriksson, Johan, Gieger, Christian, Hayward, Caroline, Jarvelin, Marjo-Riitta, McLachlan, Stela, Morris, Andrew P., Ohlsson, Claes, Pennell, Craig E., Price, Jackie, Rudan, Igor, Ruusalepp, Arno, Spector, Tim, Tiemeier, Henning, Völzke, Henry, Wilson, James F., Michoel, Tom, Timpson, Nicolas J., Smith, George Davey, and Walker, Brian R.

Published
2021
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18. Leukocytes carryingClonal Hematopoiesis of Indeterminate Potential(CHIP) Mutations invade Human Atherosclerotic Plaques

Author

Scheidt, Moritz von, primary, Bauer, Sabine, additional, Ma, Angela, additional, Hao, Ke, additional, Kessler, Thorsten, additional, Vilne, Baiba, additional, Wang, Ying, additional, Hodonsky, Chani J., additional, Ghosh, Saikat K.B., additional, Mokry, Michal, additional, Gao, Hua, additional, Kawai, Kenji, additional, Sakamoto, Atsushi, additional, Kaiser, Juliane, additional, Bongiovanni, Dario, additional, Fleig, Julia, additional, Oldenbuettel, Lilith, additional, Chen, Zhifen, additional, Moggio, Aldo, additional, Sager, Hendrik B., additional, Hecker, Judith S., additional, Bassermann, Florian, additional, Maegdefessel, Lars, additional, Miller, Clint L., additional, Koenig, Wolfgang, additional, Zeiher, Andreas M., additional, Dimmeler, Stefanie, additional, Graw, Matthias, additional, Braun, Christian, additional, Ruusalepp, Arno, additional, Leeper, Nicholas J., additional, Kovacic, Jason C., additional, Björkegren, Johan L.M., additional, and Schunkert, Heribert, additional

Published
2023
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19. Correction to: Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Author

Glicksberg, Benjamin S., Amadori, Letizia, Akers, Nicholas K., Sukhavasi, Katyayani, Franzén, Oscar, Li, Li, Belbin, Gillian M., Ayers, Kristin L., Shameer, Khader, Badgeley, Marcus A., Johnson, Kipp W., Readhead, Ben, Darrow, Bruce J., Kenny, Eimear E., Betsholtz, Christer, Ermel, Raili, Skogsberg, Josefin, Ruusalepp, Arno, Schadt, Eric E., Dudley, Joel T., Ren, Hongxia, Kovacic, Jason C., Giannarelli, Chiara, Li, Shuyu D., Björkegren, Johan L. M., and Chen, Rong

Published
2019
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20. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Jr, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M., Lin, Wei-Yu, Lindgren, Arne G., Lorentzen, Erik, Magnusson, Patrik K., Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F., Meschia, James F., Mitchell, Braxton D., Mosley, Thomas H., Nalls, Michael A., Ninomiya, Toshiharu, O’Donnell, Martin J., Psaty, Bruce M., Pulit, Sara L., Rannikmäe, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Sakaue, Saori, Sale, Michele M., Salomaa, Veikko, Sapkota, Bishwa R., Schmidt, Reinhold, Schmidt, Carsten O., Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Björkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Trégouët, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, Jr, W. T., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2018
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21. Leukocytes carrying Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutations invade Human Atherosclerotic Plaques

Author

Scheidt, Moritz von, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J., Ghosh, Saikat K.B., Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik, Hecker, Judith S., Bassermann, Florian, Mägdefessel, Lars, Miller, Clint L., Koenig, Wolfgang, Zeiher, Andreas M., Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J., Kovacic, Jason C., Björkegren, Johan L.M., Schunkert, Heribert, Scheidt, Moritz von, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J., Ghosh, Saikat K.B., Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik, Hecker, Judith S., Bassermann, Florian, Mägdefessel, Lars, Miller, Clint L., Koenig, Wolfgang, Zeiher, Andreas M., Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J., Kovacic, Jason C., Björkegren, Johan L.M., and Schunkert, Heribert

Abstract

Background: Leukocyte progenitors derived from clonal hematopoiesis of undetermined potential (CHIP) are associated with increased cardiovascular events. However, the prevalence and functional relevance of CHIP in coronary artery disease (CAD) are unclear, and cells affected by CHIP have not been detected in human atherosclerotic plaques. Methods: CHIP mutations in blood and tissues were identified by targeted deep-DNA-sequencing (DNAseq: coverage >3,000) and whole-genome-sequencing (WGS: coverage >35). CHIP-mutated leukocytes were visualized in human atherosclerotic plaques by mutaFISHTM. Functional relevance of CHIP mutations was studied by RNAseq. Results: DNAseq of whole blood from 540 deceased CAD patients of the Munich cardIovaScular StudIes biObaNk (MISSION) identified 253 (46.9%) CHIP mutation carriers (mean age 78.3 years). DNAseq on myocardium, atherosclerotic coronary and carotid arteries detected identical CHIP mutations in 18 out of 25 mutation carriers in tissue DNA. MutaFISHTM visualized individual macrophages carrying DNMT3A CHIP mutations in human atherosclerotic plaques. Studying monocyte-derived macrophages from Stockholm-Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET; n=941) by WGS revealed CHIP mutations in 14.2% (mean age 67.1 years). RNAseq of these macrophages revealed that expression patterns in CHIP mutation carriers differed substantially from those of non-carriers. Moreover, patterns were different depending on the underlying mutations, e.g. those carrying TET2 mutations predominantly displayed upregulated inflammatory signaling whereas ASXL1 mutations showed stronger effects on metabolic pathways. Conclusions: Deep-DNA-sequencing reveals a high prevalence of CHIP mutations in whole blood of CAD patients. CHIP-affected leukocytes invade plaques in human coronary arteries. RNAseq data obtained from macrophages of CHIP-affected patients suggest that pro-atherosclerotic signaling differs depending on the underlying mutation

Published
2023

22. Leukocytes carrying Clonal Hematopoiesis of Indeterminate Potential (CHIP) Mutations invade Human Atherosclerotic Plaques.

Author

CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, von Scheidt, Moritz, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J, Ghosh, Saikat K B, Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik B, Hecker, Judith S, Bassermann, Florian, Maegdefessel, Lars, Miller, Clint L, Koenig, Wolfgang, Zeiher, Andreas M, Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J, Kovacic, Jason C, Björkegren, Johan L M, Schunkert, Heribert, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Child Health, Circulatory Health, von Scheidt, Moritz, Bauer, Sabine, Ma, Angela, Hao, Ke, Kessler, Thorsten, Vilne, Baiba, Wang, Ying, Hodonsky, Chani J, Ghosh, Saikat K B, Mokry, Michal, Gao, Hua, Kawai, Kenji, Sakamoto, Atsushi, Kaiser, Juliane, Bongiovanni, Dario, Fleig, Julia, Oldenbuettel, Lilith, Chen, Zhifen, Moggio, Aldo, Sager, Hendrik B, Hecker, Judith S, Bassermann, Florian, Maegdefessel, Lars, Miller, Clint L, Koenig, Wolfgang, Zeiher, Andreas M, Dimmeler, Stefanie, Graw, Matthias, Braun, Christian, Ruusalepp, Arno, Leeper, Nicholas J, Kovacic, Jason C, Björkegren, Johan L M, and Schunkert, Heribert

Published
2023

23. Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

Author

Kleeman, Sam O; https://orcid.org/0000-0003-1720-8804, Thakir, Tuba Mansoor, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef J R A, Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Sinha, Sarthak, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz G N, Biernaskie, Jeff, Dufour, Antoine, Tober-Lau, Pinkus, Ruusalepp, Arno, Bjorkegren, Johan L M, Ralser, Markus; https://orcid.org/0000-0001-9535-7413, Kurth, Florian; https://orcid.org/0000-0002-3807-473X, Demichev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, Walker, Brian R, Meyer, Hannah V, et al, Kleeman, Sam O; https://orcid.org/0000-0003-1720-8804, Thakir, Tuba Mansoor, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef J R A, Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Sinha, Sarthak, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz G N, Biernaskie, Jeff, Dufour, Antoine, Tober-Lau, Pinkus, Ruusalepp, Arno, Bjorkegren, Johan L M, Ralser, Markus; https://orcid.org/0000-0001-9535-7413, Kurth, Florian; https://orcid.org/0000-0002-3807-473X, Demichev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, Walker, Brian R, Meyer, Hannah V, and et al

Abstract

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.

Published
2023

24. Cardiometabolic risk loci share downstream cis- and trans-gene regulation across tissues and diseases

Author

Franzén, Oscar, Ermel, Raili, Cohain, Ariella, Akers, Nicholas K., Di Narzo, Antonio, Talukdar, Husain A., Foroughi-Asl, Hassan, Giambartolomei, Claudia, Fullard, John F., Sukhavasi, Katyayani, Köks, Sulev, Gan, Li-Ming, Giannarelli, Chiara, Kovacic, Jason C., Betsholtz, Christer, Losic, Bojan, Michoel, Tom, Hao, Ke, Roussos, Panos, Skogsberg, Josefin, Ruusalepp, Arno, Schadt, Eric E., and Björkegren, Johan L. M.

Published
2016

25. Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Author

Glicksberg, Benjamin S., Amadori, Letizia, Akers, Nicholas K., Sukhavasi, Katyayani, Franzén, Oscar, Li, Li, Belbin, Gillian M., Akers, Kristin L., Shameer, Khader, Badgeley, Marcus A., Johnson, Kipp W., Readhead, Ben, Darrow, Bruce J., Kenny, Eimear E., Betsholtz, Christer, Ermel, Raili, Skogsberg, Josefin, Ruusalepp, Arno, Schadt, Eric E., Dudley, Joel T., Ren, Hongxia, Kovacic, Jason C., Giannarelli, Chiara, Li, Shuyu D., Björkegren, Johan L. M., and Chen, Rong

Published
2019
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26. Plasma cortisol-linked gene networks in hepatic and adipose tissues implicate corticosteroidbinding globulin in modulating tissue glucocorticoid action and cardiovascular risk.

Author

Bankier, Sean, Lingfei Wang, Crawford, Andrew, Morgan, Ruth A., Ruusalepp, Arno, Andrew, Ruth, Björkegren, Johan L. M., Walker, Brian R., and Michoel, Tom

Subjects
ADIPOSE tissues, LOCUS (Genetics), INTERFERON regulatory factors, CARDIOVASCULAR diseases risk factors, GENE expression, GENETIC variation, GENE regulatory networks
Abstract

Genome-wide association meta-analysis (GWAMA) by the Cortisol Network (CORNET) consortium identified genetic variants spanning the SERPINA6/SERPINA1 locus on chromosome 14 associated with morning plasma cortisol, cardiovascular disease (CVD), and SERPINA6 mRNA expression encoding corticosteroid-binding globulin (CBG) in the liver. These and other findings indicate that higher plasma cortisol levels are causally associated with CVD; however, the mechanisms by which variations in CBG lead to CVD are undetermined. Using genomic and transcriptomic data from The Stockholm Tartu Atherosclerosis Reverse Networks Engineering Task (STARNET) study, we identified plasma cortisol-linked single-nucleotide polymorphisms (SNPs) that are trans-associated with genes from seven different vascular and metabolic tissues, finding the highest representation of trans-genes in the liver, subcutaneous fat, and visceral abdominal fat, [false discovery rate (FDR) = 15%]. We identified a subset of cortisol-associated trans-genes that are putatively regulated by the glucocorticoid receptor (GR), the primary transcription factor activated by cortisol. Using causal inference, we identified GR-regulated trans-genes that are responsible for the regulation of tissuespecific gene networks. Cis-expression Quantitative Trait Loci (eQTLs) were used as genetic instruments for identification of pairwise causal relationships from which gene networks could be reconstructed. Gene networks were identified in the liver, subcutaneous fat, and visceral abdominal fat, including a high confidence gene network specific to subcutaneous adipose (FDR = 10%) under the regulation of the interferon regulatory transcription factor, IRF2. These data identify a plausible pathway through which variation in the liver CBG production perturbs cortisol-regulated gene networks in peripheral tissues and thereby promote CVD. [ABSTRACT FROM AUTHOR]

Published
2023
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27. Gene networks driven by genetic variation for plasma cortisol in hepatic and adipose tissues implicate corticosteroid binding globulin in modulating tissue glucocorticoid action and cardiovascular risk

Author

Bankier, Sean, primary, Wang, Lingfei, additional, Crawford, Andrew, additional, Morgan, Ruth A, additional, Ruusalepp, Arno, additional, Andrew, Ruth, additional, Björkegren, Johan LM, additional, Walker, Brian R, additional, and Michoel, Tom, additional

Published
2023
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28. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants

Author

Aragam, Krishna G, Jiang, Tao, Goel, Anuj, Kanoni, Stavroula, Wolford, Brooke N, Atri, Deepak S, Weeks, Elle M, Wang, Minxian, Hindy, George, Zhou, Wei, Grace, Christopher, Roselli, Carolina, Marston, Nicholas A, Kamanu, Frederick K, Surakka, Ida, Venegas, Loreto Muñoz, Sherliker, Paul, Koyama, Satoshi, Ishigaki, Kazuyoshi, Åsvold, Bjørn O, Brown, Michael R, Brumpton, Ben, De Vries, Paul S, Giannakopoulou, Olga, Giardoglou, Panagiota, Gudbjartsson, Daniel F, Güldener, Ulrich, Haider, Syed M Ijlal, Helgadottir, Anna, Ibrahim, Maysson, Kastrati, Adnan, Kessler, Thorsten, Kyriakou, Theodosios, Konopka, Tomasz, Li, Ling, Ma, Lijiang, Meitinger, Thomas, Mucha, Sören, Munz, Matthias, Murgia, Federico, Nielsen, Jonas B, Nöthen, Markus M, Pang, Shichao, Reinberger, Tobias, Schnitzler, Gavin, Smedley, Damian, Thorleifsson, Gudmar, Von Scheidt, Moritz, Ulirsch, Jacob C, Danesh, John, Arnar, David O, Burtt, Noël P, Costanzo, Maria C, Flannick, Jason, Ito, Kaoru, Jang, Dong-Keun, Kamatani, Yoichiro, Khera, Amit V, Komuro, Issei, Kullo, Iftikhar J, Lotta, Luca A, Nelson, Christopher P, Roberts, Robert, Thorgeirsson, Gudmundur, Thorsteinsdottir, Unnur, Webb, Thomas R, Baras, Aris, Björkegren, Johan LM, Boerwinkle, Eric, Dedoussis, George, Holm, Hilma, Hveem, Kristian, Melander, Olle, Morrison, Alanna C, Orho-Melander, Marju, Rallidis, Loukianos S, Ruusalepp, Arno, Sabatine, Marc S, Stefansson, Kari, Zalloua, Pierre, Ellinor, Patrick T, Farrall, Martin, Ruff, Christian T, Finucane, Hilary K, Hopewell, Jemma C, Clarke, Robert, Gupta, Rajat M, Erdmann, Jeanette, Samani, Nilesh J, Schunkert, Heribert, Watkins, Hugh, Willer, Cristen J, Deloukas, Panos, Kathiresan, Sekar, Butterworth, Adam S, Aragam, Krishna G [0000-0003-3223-9131], Goel, Anuj [0000-0003-2307-4021], Kanoni, Stavroula [0000-0002-1691-9615], Wolford, Brooke N [0000-0003-3153-1552], Atri, Deepak S [0000-0001-8139-5419], Weeks, Elle M [0000-0002-4317-4444], Wang, Minxian [0000-0002-3753-508X], Zhou, Wei [0000-0001-7719-0859], Roselli, Carolina [0000-0001-5267-6756], Kamanu, Frederick K [0000-0001-7208-1047], Koyama, Satoshi [0000-0002-9286-0360], Ishigaki, Kazuyoshi [0000-0003-2881-0657], Åsvold, Bjørn O [0000-0003-3837-2101], Brumpton, Ben [0000-0002-3058-1059], Gudbjartsson, Daniel F [0000-0002-5222-9857], Güldener, Ulrich [0000-0001-5052-8610], Helgadottir, Anna [0000-0002-1806-2467], Kessler, Thorsten [0000-0003-3326-1621], Li, Ling [0000-0002-3280-9475], Mucha, Sören [0000-0002-1647-2526], Munz, Matthias [0000-0002-4728-3357], Murgia, Federico [0000-0002-3608-845X], Pang, Shichao [0000-0002-4111-2864], Smedley, Damian [0000-0002-5836-9850], Thorleifsson, Gudmar [0000-0003-4623-9087], von Scheidt, Moritz [0000-0001-7159-8271], Ulirsch, Jacob C [0000-0002-7947-0827], Costanzo, Maria C [0000-0001-9043-693X], Flannick, Jason [0000-0002-3618-795X], Ito, Kaoru [0000-0003-1843-773X], Khera, Amit V [0000-0001-6535-5839], Komuro, Issei [0000-0002-0714-7182], Kullo, Iftikhar J [0000-0002-6524-3471], Roberts, Robert [0000-0002-6792-4633], Webb, Thomas R [0000-0001-5998-8226], Baras, Aris [0000-0002-6830-3396], Björkegren, Johan LM [0000-0003-1945-7425], Holm, Hilma [0000-0002-9517-6636], Morrison, Alanna C [0000-0001-6381-4296], Orho-Melander, Marju [0000-0002-3578-2503], Stefansson, Kari [0000-0003-1676-864X], Farrall, Martin [0000-0003-4564-2165], Finucane, Hilary K [0000-0003-3864-9828], Clarke, Robert [0000-0002-9802-8241], Erdmann, Jeanette [0000-0002-4486-6231], Samani, Nilesh J [0000-0002-3286-8133], Schunkert, Heribert [0000-0001-6428-3001], Watkins, Hugh [0000-0002-5287-9016], Willer, Cristen J [0000-0001-5645-4966], Kathiresan, Sekar [0000-0002-3711-7101], Butterworth, Adam S [0000-0002-6915-9015], and Apollo - University of Cambridge Repository

Subjects
692/699/75/2, 631/208/205/2138, article, Humans, Coronary Artery Disease, Genome-Wide Association Study
Abstract

Funder: K.G.A. has received support from the American Heart Association Institute for Precision Cardiovascular Medicine (17IFUNP3384001), a KL2/Catalyst Medical Research Investigator Training (CMeRIT) award from the Harvard Catalyst (KL2 TR002542), and the NIH (1K08HL153937)., Funder: B.N.W is supported by the National Science Foundation Graduate Research Program (DGE 1256260)., Funder: I.S. is supported by a Precision Health Scholars Award from the University of Michigan Medical School., Funder: I.K., S.Ko., and K.It. are funded by the Japan Agency for Medical Research and Development, AMED, under Grant Numbers JP16ek0109070h0003, JP18kk0205008h0003, JP18kk0205001s0703, JP20km0405209, and JP20ek0109487. The BioBank Japan is supported by AMED under Grant Number JP20km0605001., Funder: J.L.M.B. acknowledges research support from NIH R01HL125863, American Heart Association (A14SFRN20840000), the Swedish Research Council (2018-02529) and Heart Lung Foundation (20170265) and the Foundation Leducq (PlaqueOmics: Novel Roles of Smooth Muscle and Other Matrix Producing Cells in Atherosclerotic Plaque Stability and Rupture, 18CVD02., Funder: P.S.dV was supported by American Heart Association grant number 18CDA34110116 and National Heart, Lung, and Blood Institute grant R01HL146860. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I and HHSN268201700005I), R01HL087641, R01HL059367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research., Funder: O.G. has received funding from the British Heart Foundation (BHF) (FS/14/66/3129)., Funder: T.K. is supported by the Corona-Foundation (Junior Research Group Translational Cardiovascular Genomics) and the German Research Foundation (DFG) as part of the Sonderforschungsbereich SFB 1123 (B02)., Funder: D.S.A. has received support from a training grant from the NIH (T32HL007604)., Funder: N.P.B., M.C.C., J.F., and D.-K.J. have been funded by the National Institute of Diabetes and Digestive and Kidney Diseases (2UM1DK105554)., Funder: A.V.K. has been funded by 1K08HG010155 from the National Human Genome Research Institute., Funder: C.P.N. and T.R.W received funding from the British Heart Foundation (SP/16/4/32697)., Funder: The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The K.G. Jebsen Center for Genetic Epidemiology is financed by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology; and Central Norway Regional Health Authority. Whole genome sequencing for the HUNT study was funded by HL109946., Funder: O.M. was funded by the Swedish Heart- and Lung Foundation, the Swedish Research Council, the European Research Council ERC-AdG-2019-885003 and Lund University Infrastructure grant ”Malmö population-based cohorts” (STYR 2019/2046)., Funder: This work was supported by the European Commission (HEALTH-F2–2013-601456) and the TriPartite Immunometabolism Consortium [TrIC]- NovoNordisk Foundation (NNF15CC0018486), VIAgenomics (SP/19/2/344612), the British Heart Foundation, a Wellcome Trust core award (M.F., H.W., 203141/Z/16/Z) and support from the NIHR Oxford Biomedical Research Centre. M.F. and H.W. are members of the Oxford BHF Centre of Research Excellence (RE/13/1/30181). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health., Funder: J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator., Funder: J.C.H. acknowledges personal funding from the British Heart Foundation (FS/14/55/30806) and is a member of the Oxford BHF Centre of Research Excellence (RE/13/1/30181)., Funder: R.C. has received funding from the British Heart Foundation and British Heart Foundation Centre of Research Excellence., Funder: This research was supported by BHF (SP/13/2/30111) and conducted using the UK Biobank Resource (application number 9922)., Funder: The GerMIFs gratefully acknowledge the support of the Bavarian State Ministry of Health and Care, furthermore founded this work within its framework of DigiMed Bayern (grant No: DMB-1805-0001), the German Federal Ministry of Education and Research (BMBF) within the framework of ERA-NET on Cardiovascular Disease (Druggable-MI-genes: 01KL1802), within the scheme of target validation (BlockCAD: 16GW0198K), within the framework of the e:Med research and funding concept (AbCD-Net: 01ZX1706C), the British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK)-collaboration (VIAgenomics) and the German Research Foundation (DFG) as part of the Sonderforschungsbereich SFB 1123 (B02) and the Sonderforschungsbereich SFB TRR 267 (B05)., Funder: C.J.W. is funded by NIH grant R35-HL135824., Funder: This work was supported by the British Heart Foundation (BHF) grant RG/14/5/30893 (P.D.) and forms part of the research themes contributing to the translational research portfolios of the Barts Biomedical Research Centre funded by the UK National Institute for Health Research (NIHR)., The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD.

Published
2022
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29. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Jr, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M., Lin, Wei-Yu, Lindgren, Arne G., Lorentzen, Erik, Magnusson, Patrik K., Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F., Meschia, James F., Mitchell, Braxton D., Mosley, Thomas H., Nalls, Michael A., Ninomiya, Toshiharu, O’Donnell, Martin J., Psaty, Bruce M., Pulit, Sara L., Rannikmäe, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Sakaue, Saori, Sale, Michele M., Salomaa, Veikko, Sapkota, Bishwa R., Schmidt, Reinhold, Schmidt, Carsten O., Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Björkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Trégouët, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium (ISGC), METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network (SiGN), UK Young Lacunar DNA Study, MEGASTROKE Consortium, Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, Jr, W. T., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2019
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30. The HDAC9-associated risk locus promotes coronary artery disease by governing TWIST1

Author

Ma, Lijiang, primary, Bryce, Nicole S., additional, Turner, Adam W., additional, Di Narzo, Antonio F., additional, Rahman, Karishma, additional, Xu, Yang, additional, Ermel, Raili, additional, Sukhavasi, Katyayani, additional, d’Escamard, Valentina, additional, Chandel, Nirupama, additional, V’Gangula, Bhargavi, additional, Wolhuter, Kathryn, additional, Kadian-Dodov, Daniella, additional, Franzen, Oscar, additional, Ruusalepp, Arno, additional, Hao, Ke, additional, Miller, Clint L., additional, Björkegren, Johan L. M., additional, and Kovacic, Jason C., additional

Published
2022
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32. Cystatin C is glucocorticoid-responsive, directs recruitment of Trem2+ macrophages and predicts failure of cancer immunotherapy

Author

Kleeman, Sam O, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef JRA, Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz GN, Biernaskie, Jeff, Dufour, Antoine, Pinkus, Tober-Lau, Ruusalepp, Arno, Bjorkegren, Johan LM, Ralser, Markus, Kurth, Florian, Demechev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, Walker, Brian R, Meyer, Hannah V, Janowitz, Tobias, Kleeman, Sam O, Demestichas, Breanna, Mourikis, Nicholas, Loiero, Dominik, Ferrer, Miriam, Bankier, Sean, Riazat-Kesh, Yosef JRA, Lee, Hassal, Chantzichristos, Dimitrios, Regan, Claire, Preall, Jonathan, Rosin, Nicole, Yipp, Bryan, de Almeida, Luiz GN, Biernaskie, Jeff, Dufour, Antoine, Pinkus, Tober-Lau, Ruusalepp, Arno, Bjorkegren, Johan LM, Ralser, Markus, Kurth, Florian, Demechev, Vadim, Heywood, Todd, Gao, Qing, Johannsson, Gudmundur, Koelzer, Viktor H; https://orcid.org/0000-0001-9206-4885, Walker, Brian R, Meyer, Hannah V, and Janowitz, Tobias

Abstract

Cystatin C (CyC) is a secreted cysteine protease inhibitor and its biological functions remain insufficiently characterized. Plasma CyC is elevated in many patients, especially when receiving glucocorticoid (GC) treatment. Endogenous GCs are essential for life and are appropriately upregulated in response to systemic stress. Here we empirically connect GCs with systemic regulation of CyC. We used genome-wide association and structural equation modeling to determine the genetics of the latent trait CyC production in UK Biobank. CyC production and a polygenic score (PGS) capturing germline predisposition to CyC production predicted elevated all-cause and cancer-specific mortality. We then demonstrated that CyC is a direct target of GC receptor, with GC-responsive CyC secretion exhibited by macrophages and cancer cells. Using isogenic CyC-knockout tumors, we discovered a markedly attenuated tumor growth in vivo and found abrogated recruitment of Trem2+ macrophages, which have been previously linked to failure of cancer immunotherapy. Finally, we showed that the CyC-production PGS predicted checkpoint immunotherapy failure in a combined clinical trial cohort of 685 metastatic cancer patients. Taken together, our results demonstrate that CyC may be a direct effector of GC-induced immunosuppression, acting through recruitment of Trem2+ macrophages, and therefore could be a target for combination cancer immunotherapy.

Published
2022

33. Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

Author

Jones, Gregory T., Tromp, Gerard, Kuivaniemi, Helena, Gretarsdottir, Solveig, Baas, Annette F., Giusti, Betti, Strauss, Ewa, van‘t Hof, Femke N.G., Webb, Thomas R., Erdman, Robert, Ritchie, Marylyn D., Elmore, James R., Verma, Anurag, Pendergrass, Sarah, Kullo, Iftikhar J., Ye, Zi, Peissig, Peggy L., Gottesman, Omri, Verma, Shefali S., Malinowski, Jennifer, Rasmussen-Torvik, Laura J., Borthwick, Kenneth M., Smelser, Diane T., Crosslin, David R., de Andrade, Mariza, Ryer, Evan J., McCarty, Catherine A., Böttinger, Erwin P., Pacheco, Jennifer A., Crawford, Dana C., Carrell, David S., Gerhard, Glenn S., Franklin, David P., Carey, David J., Phillips, Victoria L., Williams, Michael J.A., Wei, Wenhua, Blair, Ross, Hill, Andrew A., Vasudevan, Thodor M., Lewis, David R., Thomson, Ian A., Krysa, Jo, Hill, Geraldine B., Roake, Justin, Merriman, Tony R., Oszkinis, Grzegorz, Galora, Silvia, Saracini, Claudia, Abbate, Rosanna, Pulli, Raffaele, Pratesi, Carlo, Saratzis, Athanasios, Verissimo, Ana R., Bumpstead, Suzannah, Badger, Stephen A., Clough, Rachel E., Cockerill, Gillian, Hafez, Hany, Scott, D. Julian A., Futers, T. Simon, Romaine, Simon P.R., Bridge, Katherine, Griffin, Kathryn J., Bailey, Marc A., Smith, Alberto, Thompson, Matthew M., van Bockxmeer, Frank M., Matthiasson, Stefan E., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Blankensteijn, Jan D., Teijink, Joep A.W., Wijmenga, Cisca, de Graaf, Jacqueline, Kiemeney, Lambertus A., Lindholt, Jes S., Hughes, Anne, Bradley, Declan T., Stirrups, Kathleen, Golledge, Jonathan, Norman, Paul E., Powell, Janet T., Humphries, Steve E., Hamby, Stephen E., Goodall, Alison H., Nelson, Christopher P., Sakalihasan, Natzi, Courtois, Audrey, Ferrell, Robert E., Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Eicher, John D., Johnson, Andrew D., Betsholtz, Christer, Ruusalepp, Arno, Franzén, Oscar, Schadt, Eric E., Björkegren, Johan L.M., Lipovich, Leonard, Drolet, Anne M., Verhoeven, Eric L., Zeebregts, Clark J., Geelkerken, Robert H., van Sambeek, Marc R., van Sterkenburg, Steven M., de Vries, Jean-Paul, Stefansson, Kari, Thompson, John R., de Bakker, Paul I.W., Deloukas, Panos, Sayers, Robert D., Harrison, Seamus C., van Rij, Andre M., Samani, Nilesh J., and Bown, Matthew J.

Published
2017
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34. Integrative Prioritization of Causal Genes for Coronary Artery Disease

Author

Hao, Ke, primary, Ermel, Raili, additional, Sukhavasi, Katyayani, additional, Cheng, Haoxiang, additional, Ma, Lijiang, additional, Li, Ling, additional, Amadori, Letizia, additional, Koplev, Simon, additional, Franzén, Oscar, additional, d’Escamard, Valentina, additional, Chandel, Nirupama, additional, Wolhuter, Kathryn, additional, Bryce, Nicole S., additional, Venkata, Vamsidhar R.M., additional, Miller, Clint L., additional, Ruusalepp, Arno, additional, Schunkert, Heribert, additional, Björkegren, Johan L.M., additional, and Kovacic, Jason C., additional

Published
2022
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36. Cystatin C is glucocorticoid-responsive, directs recruitment of Trem2+ macrophages and predicts failure of cancer immunotherapy

Author

Kleeman, Sam O., primary, Demestichas, Breanna, additional, Mourikis, Nicholas, additional, Loiero, Dominik, additional, Ferrer, Miriam, additional, Bankier, Sean, additional, Riazat-Kesh, Yosef J.R.A., additional, Lee, Hassal, additional, Chantzichristos, Dimitrios, additional, Regan, Claire, additional, Preall, Jonathan, additional, Sinha, Sarthak, additional, Rosin, Nicole, additional, Yipp, Bryan, additional, de Almeida, Luiz G.N., additional, Biernaskie, Jeff, additional, Dufour, Antoine, additional, Tober-Lau, Pinkus, additional, Ruusalepp, Arno, additional, Bjorkegren, Johan L. M., additional, Ralser, Markus, additional, Kurth, Florian, additional, Demechev, Vadim, additional, Heywood, Todd, additional, Gao, Qing, additional, Johannsson, Gudmundur, additional, Koelzer, Viktor H., additional, Walker, Brian R., additional, Meyer, Hannah V., additional, and Janowitz, Tobias, additional

Published
2021
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37. Transcriptome wide association study of coronary artery disease identifies novel susceptibility genes

Author

Schunkert, Heribert, primary, Li, Ling, additional, Chen, Zhifen, additional, Scheidt, Moritz, additional, Steiner, Andrea, additional, Güldener, Ulrich, additional, Koplev, Simon, additional, Ma, Angela, additional, Hao, Ke, additional, Pan, Calvin, additional, Lusis, Aldons, additional, Pang, Shichao, additional, Kessler, Thorsten, additional, Ermel, Raili, additional, Sukhavasi, Katyayani, additional, Ruusalepp, Arno, additional, Gagneur, Julien, additional, Erdmann, Jeanette, additional, Kovacic, Jason, additional, and Bjorkegren, Johan, additional

Published
2021
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38. Transcriptome wide association study of coronary artery disease identifies novel susceptibility genes

Author

Li, Ling, primary, Chen, Zhifen, additional, von Scheidt, Moritz, additional, Steiner, Andrea, additional, Güldener, Ulrich, additional, Koplev, Simon, additional, Ma, Angela, additional, Hao, Ke, additional, Pan, Calvin, additional, Lusis, Aldons J., additional, Pang, Shichao, additional, Kessler, Thorsten, additional, Ermel, Raili, additional, Sukhavasi, Katyayani, additional, Ruusalepp, Arno, additional, Gagneur, Julien, additional, Erdmann, Jeanette, additional, Kovacic, Jason C., additional, Björkegren, Johan L.M., additional, and Schunkert, Heribert, additional

Published
2021
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40. Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade

Author

Electrofysiologie, CDL Onderzoek Pasterkamp, Circulatory Health, Wang, Ying, Nanda, Vivek, Direnzo, Daniel, Ye, Jianqin, Xiao, Sophia, Kojima, Yoko, Howe, Kathryn L., Jarr, Kai Uwe, Flores, Alyssa M., Tsantilas, Pavlos, Tsao, Noah, Rao, Abhiram, Newman, Alexandra A.C., Eberhard, Anne V., Priest, James R., Ruusalepp, Arno, Pasterkamp, Gerard, Maegdefessel, Lars, Miller, Clint L., Lind, Lars, Koplev, Simon, Björkegren, Johan L.M., Owens, Gary K., Ingelsson, Erik, Weissman, Irving L., Leeper, Nicholas J., Electrofysiologie, CDL Onderzoek Pasterkamp, Circulatory Health, Wang, Ying, Nanda, Vivek, Direnzo, Daniel, Ye, Jianqin, Xiao, Sophia, Kojima, Yoko, Howe, Kathryn L., Jarr, Kai Uwe, Flores, Alyssa M., Tsantilas, Pavlos, Tsao, Noah, Rao, Abhiram, Newman, Alexandra A.C., Eberhard, Anne V., Priest, James R., Ruusalepp, Arno, Pasterkamp, Gerard, Maegdefessel, Lars, Miller, Clint L., Lind, Lars, Koplev, Simon, Björkegren, Johan L.M., Owens, Gary K., Ingelsson, Erik, Weissman, Irving L., and Leeper, Nicholas J.

Published
2020

41. OR09-04 Common Genetic Variants Associated with SERPINA6 Expression in Liver Influence Cortisol-Responsive Transcriptional Networks in Human Adipose Tissue

Author

Bankier, Sean A, primary, Crawford, Andrew A, primary, Wang, Lingfei, primary, Sukhavasi, Katyayani, primary, Ermel, Raili, primary, Andrew, Ruth, primary, Ruusalepp, Arno, primary, Timpson, Nicolas J, primary, Smith, George Davey, primary, Bjorkegren, Johan L M, primary, Walker, Brian R, primary, and Michoel, Tom, primary

Published
2020
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43. Additional file 1: of Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits

Author

Glicksberg, Benjamin, Amadori, Letizia, Akers, Nicholas, Katyayani Sukhavasi, FranzĂŠn, Oscar, Li, Li, Belbin, Gillian, Akers, Kristin, Khader Shameer, Badgeley, Marcus, Johnson, Kipp, Readhead, Ben, Darrow, Bruce, Kenny, Eimear, Betsholtz, Christer, Ermel, Raili, Skogsberg, Josefin, Ruusalepp, Arno, Schadt, Eric, Dudley, Joel, Hongxia Ren, Kovacic, Jason, Giannarelli, Chiara, Shuyu Li, BjĂśrkegren, Johan, and Chen, Rong

Abstract

Supplementary Material, Supplementary Methods, Supplementary Results, Supplementary Discussion, Supplementary Figure legends, Supplementary Table legends; Figures S1-S9. (PDF 8049â kb)

Published
2019
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46. Genetic regulation of the placental transcriptome underlies birth weight and risk of childhood obesity

Author

Peng, Shouneng, primary, Deyssenroth, Maya A., additional, Di Narzo, Antonio F., additional, Cheng, Haoxiang, additional, Zhang, Zhongyang, additional, Lambertini, Luca, additional, Ruusalepp, Arno, additional, Kovacic, Jason C., additional, Bjorkegren, Johan L. M., additional, Marsit, Carmen J., additional, Chen, Jia, additional, and Hao, Ke, additional

Published
2018
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47. Release of Mitochondrial and Nuclear DNA During On-Pump Heart Surgery: Kinetics and Relation to Extracellular Vesicles

Author

Baysa, Anton, primary, Fedorov, Anton, additional, Kondratov, Kirill, additional, Ruusalepp, Arno, additional, Minasian, Sarkis, additional, Galagudza, Michael, additional, Popov, Maxim, additional, Kurapeev, Dmitry, additional, Yakovlev, Alexey, additional, Valen, Guro, additional, Kostareva, Anna, additional, Vaage, Jarle, additional, and Stensløkken, Kåre-Olav, additional

Published
2018
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48. Functional regulatory mechanism of smooth muscle cell-restricted LMOD1 coronary artery disease locus

Author

Nanda, Vivek, primary, Wang, Ting, additional, Pjanic, Milos, additional, Liu, Boxiang, additional, Nguyen, Trieu, additional, Matic, Ljubica Perisic, additional, Hedin, Ulf, additional, Koplev, Simon, additional, Ma, Lijiang, additional, Franzén, Oscar, additional, Ruusalepp, Arno, additional, Schadt, Eric E., additional, Björkegren, Johan L. M., additional, Montgomery, Stephen B., additional, Snyder, Michael P., additional, Quertermous, Thomas, additional, Leeper, Nicholas J., additional, and Miller, Clint L., additional

Published
2018
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49. Global analysis of A-to-I RNA editing reveals association with common disease variants

Author

Franzen, Oscar, Ermel, Raili, Sukhavasi, Katyayani, Jain, Rajeev, Jain, Anamika, Betsholtz, Christer, Giannarelli, Chiara, Kovacic, Jason C., Ruusalepp, Arno, Skogsberg, Josefin, Hao, Ke, Schadt, Eric E., Bjoerkegren, Johan L. M., Franzen, Oscar, Ermel, Raili, Sukhavasi, Katyayani, Jain, Rajeev, Jain, Anamika, Betsholtz, Christer, Giannarelli, Chiara, Kovacic, Jason C., Ruusalepp, Arno, Skogsberg, Josefin, Hao, Ke, Schadt, Eric E., and Bjoerkegren, Johan L. M.

Abstract

RNA editing modifies transcripts and may alter their regulation or function. In humans, the most common modification is adenosine to inosine (A-to-I). We examined the global characteristics of RNA editing in 4,301 human tissue samples. More than 1.6 million A-to-I edits were identified in 62% of all protein-coding transcripts. mRNA recoding was extremely rare; only 11 novel recoding sites were uncovered. Thirty single nucleotide polymorphisms from genome-wide association studies were associated with RNA editing; one that influences type 2 diabetes (rs2028299) was associated with editing in ARPIN. Twenty-five genes, including LRP11 and PLIN5, had editing sites that were associated with plasma lipid levels. Our findings provide new insights into the genetic regulation of RNA editing and establish a rich catalogue for further exploration of this process.

Published
2018
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50. Network analysis of coronary artery disease risk genes elucidates disease mechanisms and druggable targets

Author

Lempiäinen, Harri, Brænne, Ingrid, Michoel, Tom, Tragante, Vinicius, Vilne, Baiba, Webb, Tom R., Kyriakou, Theodosios, Eichner, Johannes, Zeng, Lingyao, Willenborg, Christina, Franzen, Oscar, Ruusalepp, Arno, Goel, Anuj, Van Der Laan, Sander W., Biegert, Claudia, Hamby, Stephen, Talukdar, Husain A., Foroughi Asl, Hassan, Dichgans, Martin, Dreker, Tobias, Graettinger, Mira, Gribbon, Philip, Kessler, Thorsten, Malik, Rainer, Prestel, Matthias, Stiller, Barbara, Schofield, Christine, Pasterkamp, Gerard, Watkins, Hugh, Samani, Nilesh J., Wittenberger, Timo, Erdmann, Jeanette, Schunkert, Heribert, Asselbergs, Folkert W., Björkegren, Johan L.M., Lempiäinen, Harri, Brænne, Ingrid, Michoel, Tom, Tragante, Vinicius, Vilne, Baiba, Webb, Tom R., Kyriakou, Theodosios, Eichner, Johannes, Zeng, Lingyao, Willenborg, Christina, Franzen, Oscar, Ruusalepp, Arno, Goel, Anuj, Van Der Laan, Sander W., Biegert, Claudia, Hamby, Stephen, Talukdar, Husain A., Foroughi Asl, Hassan, Dichgans, Martin, Dreker, Tobias, Graettinger, Mira, Gribbon, Philip, Kessler, Thorsten, Malik, Rainer, Prestel, Matthias, Stiller, Barbara, Schofield, Christine, Pasterkamp, Gerard, Watkins, Hugh, Samani, Nilesh J., Wittenberger, Timo, Erdmann, Jeanette, Schunkert, Heribert, Asselbergs, Folkert W., and Björkegren, Johan L.M.

Published
2018

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