670 results on '"Trégouët, David-Alexandre"'
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2. Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience
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Jurgens, Sean J., Rämö, Joel T., Kramarenko, Daria R., Wijdeveld, Leonoor F. J. M., Haas, Jan, Chaffin, Mark D., Garnier, Sophie, Gaziano, Liam, Weng, Lu-Chen, Lipov, Alex, Zheng, Sean L., Henry, Albert, Huffman, Jennifer E., Challa, Saketh, Rühle, Frank, Verdugo, Carmen Diaz, Krijger Juárez, Christian, Kany, Shinwan, van Orsouw, Constance A., Biddinger, Kiran, Poel, Edwin, Elliott, Amanda L., Wang, Xin, Francis, Catherine, Ruan, Richard, Koyama, Satoshi, Beekman, Leander, Zimmerman, Dominic S., Deleuze, Jean-François, Villard, Eric, Trégouët, David-Alexandre, Isnard, Richard, Boomsma, Dorret I., de Geus, Eco J. C., Tadros, Rafik, Pinto, Yigal M., Wilde, Arthur A. M., Hottenga, Jouke-Jan, Sinisalo, Juha, Niiranen, Teemu, Walsh, Roddy, Schmidt, Amand F., Choi, Seung Hoan, Chang, Kyong-Mi, Tsao, Philip S., Matthews, Paul M., Ware, James S., Lumbers, R. Thomas, van der Crabben, Saskia, Laukkanen, Jari, Palotie, Aarno, Amin, Ahmad S., Charron, Philippe, Meder, Benjamin, Ellinor, Patrick T., Daly, Mark, Aragam, Krishna G., and Bezzina, Connie R.
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- 2024
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3. Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy
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Zheng, Sean L., Henry, Albert, Cannie, Douglas, Lee, Michael, Miller, David, McGurk, Kathryn A., Bond, Isabelle, Xu, Xiao, Issa, Hanane, Francis, Catherine, De Marvao, Antonio, Theotokis, Pantazis I., Buchan, Rachel J., Speed, Doug, Abner, Erik, Adams, Lance, Aragam, Krishna G., Ärnlöv, Johan, Raja, Anna Axelsson, Backman, Joshua D., Baksi, John, Barton, Paul J. R., Biddinger, Kiran J., Boersma, Eric, Brandimarto, Jeffrey, Brunak, Søren, Bundgaard, Henning, Carey, David J., Charron, Philippe, Cook, James P., Cook, Stuart A., Denaxas, Spiros, Deleuze, Jean-François, Doney, Alexander S., Elliott, Perry, Erikstrup, Christian, Esko, Tõnu, Farber-Eger, Eric H., Finan, Chris, Garnier, Sophie, Ghouse, Jonas, Giedraitis, Vilmantas, Guðbjartsson, Daniel F., Haggerty, Christopher M., Halliday, Brian P., Helgadottir, Anna, Hemingway, Harry, Hillege, Hans L., Kardys, Isabella, Lind, Lars, Lindgren, Cecilia M., Lowery, Brandon D., Manisty, Charlotte, Margulies, Kenneth B., Moon, James C., Mordi, Ify R., Morley, Michael P., Morris, Andrew D., Morris, Andrew P., Morton, Lori, Noursadeghi, Mahdad, Ostrowski, Sisse R., Owens, Anjali T., Palmer, Colin N. A., Pantazis, Antonis, Pedersen, Ole B. V., Prasad, Sanjay K., Shekhar, Akshay, Smelser, Diane T., Srinivasan, Sundararajan, Stefansson, Kari, Sveinbjörnsson, Garðar, Syrris, Petros, Tammesoo, Mari-Liis, Tayal, Upasana, Teder-Laving, Maris, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Tragante, Vinicius, Trégouët, David-Alexandre, Treibel, Thomas A., Ullum, Henrik, Valdes, Ana M., van Setten, Jessica, van Vugt, Marion, Veluchamy, Abirami, Verschuren, W. M. Monique, Villard, Eric, Yang, Yifan, Asselbergs, Folkert W., Cappola, Thomas P., Dube, Marie-Pierre, Dunn, Michael E., Ellinor, Patrick T., Hingorani, Aroon D., Lang, Chim C., Samani, Nilesh J., Shah, Svati H., Smith, J. Gustav, Vasan, Ramachandran S., O’Regan, Declan P., Holm, Hilma, Noseda, Michela, Wells, Quinn, Ware, James S., and Lumbers, R. Thomas
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- 2024
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4. Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease
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Garcia, Geoffrey, Labrouche-Colomer, Sylvie, Duvignaud, Alexandre, Clequin, Etienne, Dussiau, Charles, Trégouët, David-Alexandre, Malvy, Denis, Prevel, Renaud, Zouine, Atika, Pellegrin, Isabelle, Goret, Julien, Mamani-Matsuda, Maria, Dewitte, Antoine, and James, Chloe
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- 2024
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5. DNA methylation analysis is used to identify novel genetic loci associated with circulating fibrinogen levels in blood.
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Hahn, Julie, Bressler, Jan, Domingo-Relloso, Arce, Chen, Ming-Huei, McCartney, Daniel, Teumer, Alexander, van Dongen, Jenny, Kleber, Marcus, Aïssi, Dylan, Swenson, Brenton, Yao, Jie, Zhao, Wei, Huang, Jian, Xia, Yujing, Brown, Michael, Costeira, Ricardo, de Geus, Eco, Delgado, Graciela, Dobson, DreVon, Elliott, Paul, Grabe, Hans, Guo, Xiuqing, Harris, Sarah, Huffman, Jennifer, Kardia, Sharon, Liu, Yongmei, Lorkowski, Stefan, Marioni, Riccardo, Nauck, Matthias, Ratliff, Scott, Sabater-Lleal, Maria, Spector, Tim, Suchon, Pierre, Taylor, Kent, Thibord, Florian, Trégouët, David-Alexandre, Wiggins, Kerri, Willemsen, Gonneke, Bell, Jordana, Boomsma, Dorret, Cole, Shelley, Cox, Simon, Dehghan, Abbas, Greinacher, Andreas, Haack, Karin, März, Winfried, Morange, Pierre-Emmanuel, Rotter, Jerome, Sotoodehnia, Nona, Tellez-Plaza, Maria, Navas-Acien, Ana, Smith, Jennifer, Johnson, Andrew, Fornage, Myriam, Smith, Nicholas, Wolberg, Alisa, Morrison, Alanna, and de Vries, Paul
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DNA methylation ,Mendelian randomization ,epigenome-wide association study ,fibrinogen ,inflammation ,Humans ,DNA Methylation ,Epigenesis ,Genetic ,Genome-Wide Association Study ,Genetic Loci ,Inflammation ,Fibrinogen ,CpG Islands - Abstract
BACKGROUND: Fibrinogen plays an essential role in blood coagulation and inflammation. Circulating fibrinogen levels may be determined based on interindividual differences in DNA methylation at cytosine-phosphate-guanine (CpG) sites and vice versa. OBJECTIVES: To perform an EWAS to examine an association between blood DNA methylation levels and circulating fibrinogen levels to better understand its biological and pathophysiological actions. METHODS: We performed an epigenome-wide association study of circulating fibrinogen levels in 18 037 White, Black, American Indian, and Hispanic participants, representing 14 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Circulating leukocyte DNA methylation was measured using the Illumina 450K array in 12 904 participants and using the EPIC array in 5133 participants. In each study, an epigenome-wide association study of fibrinogen was performed using linear mixed models adjusted for potential confounders. Study-specific results were combined using array-specific meta-analysis, followed by cross-replication of epigenome-wide significant associations. We compared models with and without CRP adjustment to examine the role of inflammation. RESULTS: We identified 208 and 87 significant CpG sites associated with fibrinogen levels from the 450K (p < 1.03 × 10-7) and EPIC arrays (p < 5.78 × 10-8), respectively. There were 78 associations from the 450K array that replicated in the EPIC array and 26 vice versa. After accounting for overlapping sites, there were 83 replicated CpG sites located in 61 loci, of which only 4 have been previously reported for fibrinogen. The examples of genes located near these CpG sites were SOCS3 and AIM2, which are involved in inflammatory pathways. The associations of all 83 replicated CpG sites were attenuated after CRP adjustment, although many remained significant. CONCLUSION: We identified 83 CpG sites associated with circulating fibrinogen levels. These associations are partially driven by inflammatory pathways shared by both fibrinogen and CRP.
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- 2023
6. Assessment of a next generation sequencing gene panel strategy in 133 patients with negative thrombophilia screening
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Suchon, Pierre, Soukarieh, Omar, Bernard, Clara, Mariotti, Antoine, Ernest, Vincent, Barthet, Marie-Christine, Saut, Noémie, Theron, Alexandre, Biron-Andréani, Christine, Daniel, Mélanie Y., Catella, Judith, Rohrlich, Pierre-Simon, Blanc-Jouvan, Florence, Le Cam Duchez, Véronique, Dari, Loubna, Trégouët, David-Alexandre, and Morange, Pierre-Emmanuel
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- 2025
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7. High risk of long-term recurrence after a first episode of venous thromboembolism during pregnancy or postpartum: the REcurrence after a PrEgnAncy related Thrombosis (REPEAT) Study
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Ibrahim-Kosta, Manal, El Harake, Sarah, Leclercq, Barbara, De Mari, Céline, Secondi, Jean-François, Paoletti, Emilie, Suchon, Pierre, Benredouane, Yasmine, Brunet, Dominique, Barthet, Marie-Christine, Bruzelius, Maria, Munsch, Gaëlle, Trégouët, David-Alexandre, Morange, Pierre-Emmanuel, Goumidi, Louisa, and Sarlon-Bartoli, Gabrielle
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- 2025
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8. Sex-specific DNA methylation marks associated with sex-biased risk of recurrence in unprovoked venous thromboembolism
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Bezerra, Ohanna C.L., Rodger, Marc, Munsch, Gaëlle, Kovacs, Michael J., Le Gal, Grégoire, Morange, Pierre-Emmanuel, Trégouët, David-Alexandre, Greenwood, Celia M.T., and Gagnon, France
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- 2025
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9. Publisher Correction: Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience
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Jurgens, Sean J., Rämö, Joel T., Kramarenko, Daria R., Wijdeveld, Leonoor F. J. M., Haas, Jan, Chaffin, Mark D., Garnier, Sophie, Gaziano, Liam, Weng, Lu-Chen, Lipov, Alex, Zheng, Sean L., Henry, Albert, Huffman, Jennifer E., Challa, Saketh, Rühle, Frank, Verdugo, Carmen Diaz, Krijger Juárez, Christian, Kany, Shinwan, van Orsouw, Constance A., Biddinger, Kiran, Poel, Edwin, Elliott, Amanda L., Wang, Xin, Francis, Catherine, Ruan, Richard, Koyama, Satoshi, Beekman, Leander, Zimmerman, Dominic S., Deleuze, Jean-François, Villard, Eric, Trégouët, David-Alexandre, Isnard, Richard, Boomsma, Dorret I., de Geus, Eco J. C., Tadros, Rafik, Pinto, Yigal M., Wilde, Arthur A. M., Hottenga, Jouke-Jan, Sinisalo, Juha, Niiranen, Teemu, Walsh, Roddy, Schmidt, Amand F., Choi, Seung Hoan, Chang, Kyong-Mi, Tsao, Philip S., Matthews, Paul M., Ware, James S., Lumbers, R. Thomas, van der Crabben, Saskia, Laukkanen, Jari, Palotie, Aarno, Amin, Ahmad S., Charron, Philippe, Meder, Benjamin, Ellinor, Patrick T., Daly, Mark, Aragam, Krishna G., and Bezzina, Connie R.
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- 2024
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10. Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension
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Hong, Jason, Medzikovic, Lejla, Sun, Wasila, Wong, Brenda, Ruffenach, Grégoire, Rhodes, Christopher J., Brownstein, Adam, Liang, Lloyd L., Aryan, Laila, Li, Min, Vadgama, Arjun, Kurt, Zeyneb, Schwantes-An, Tae-Hwi, Mickler, Elizabeth A., Gräf, Stefan, Eyries, Mélanie, Lutz, Katie A., Pauciulo, Michael W., Trembath, Richard C., Perros, Frédéric, Montani, David, Morrell, Nicholas W., Soubrier, Florent, Wilkins, Martin R., Nichols, William C., Aldred, Micheala A., Desai, Ankit A., Trégouët, David-Alexandre, Umar, Soban, Saggar, Rajan, Channick, Richard, Tuder, Rubin M., Geraci, Mark W., Stearman, Robert S., Yang, Xia, and Eghbali, Mansoureh
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- 2024
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11. Whole-genome analysis of plasma fibrinogen reveals population-differentiated genetic regulators with putative liver roles
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Huffman, Jennifer E., Nicholas, Jayna, Hahn, Julie, Heath, Adam S., Raffield, Laura M., Yanek, Lisa R., Brody, Jennifer A., Thibord, Florian, Almasy, Laura, Bartz, Traci M., Bielak, Lawrence F., Bowler, Russell P., Carrasquilla, Germán D., Chasman, Daniel I., Chen, Ming-Huei, Emmert, David B., Ghanbari, Mohsen, Haessler, Jeffrey, Hottenga, Jouke-Jan, Kleber, Marcus E., Le, Ngoc-Quynh, Lee, Jiwon, Lewis, Joshua P., Li-Gao, Ruifang, Luan, Jian'an, Malmberg, Anni, Mangino, Massimo, Marioni, Riccardo E., Martinez-Perez, Angel, Pankratz, Nathan, Polasek, Ozren, Richmond, Anne, Rodriguez, Benjamin A. T., Rotter, Jerome I., Steri, Maristella, Suchon, Pierre, Trompet, Stella, Weiss, Stefan, Zare, Marjan, Auer, Paul, Cho, Michael H., Christofidou, Paraskevi, Davies, Gail, de Geus, Eco, Deleuze, Jean-François, Delgado, Graciela E., Ekunwe, Lynette, Faraday, Nauder, Gögele, Martin, Greinacher, Andreas, Gao, He, Howard, Tom, Joshi, Peter K., Kilpeläinen, Tuomas O., Lahti, Jari, Linneberg, Allan, Naitza, Silvia, Noordam, Raymond, Paüls-Vergés, Ferran, Rich, Stephen S., Rosendaal, Frits R., Rudan, Igor, Ryan, Kathleen A., Souto, Juan Carlos, van Rooij, Frank J. A., Wang, Heming, Zhao, Wei, Becker, Lewis C., Beswick, Andrew, Brown, Michael R., Cade, Brian E., Campbell, Harry, Cho, Kelly, Crapo, James D., Curran, Joanne E., de Maat, Moniek P. M., Doyle, Margaret, Elliott, Paul, Floyd, James S., Fuchsberger, Christian, Grarup, Niels, Guo, Xiuqing, Harris, Sarah E., Hou, Lifang, Kolcic, Ivana, Kooperberg, Charles, Menni, Cristina, Nauck, Matthias, O'Connell, Jeffrey R., Orrù, Valeria, Psaty, Bruce M., Räikkönen, Katri, Smith, Jennifer A., Soria, Jose Manuel, Stott, David J., van Hylckama Vlieg, Astrid, Watkins, Hugh, Willemsen, Gonneke, Wilson, Peter W. F., Ben-Shlomo, Yoav, Blangero, John, Boomsma, Dorret, Cox, Simon R., Dehghan, Abbas, Eriksson, Johan G., Fiorillo, Edoardo, Fornage, Myriam, Hansen, Torben, Hayward, Caroline, Ikram, M. Arfan, Jukema, J. Wouter, Kardia, Sharon L. R., Lange, Leslie A., März, Winfried, Mathias, Rasika A., Mitchell, Braxton D., Mook-Kanamori, Dennis O., Morange, Pierre-Emmanuel, Pedersen, Oluf, Pramstaller, Peter P., Redline, Susan, Reiner, Alexander, Ridker, Paul M., Silverman, Edwin K., Spector, Tim D., Völker, Uwe, Wareham, Nicholas J., Wilson, James F., Yao, Jie, Trégouët, David-Alexandre, Johnson, Andrew D., Wolberg, Alisa S., de Vries, Paul S., Sabater-Lleal, Maria, Morrison, Alanna C., and Smith, Nicholas L.
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- 2024
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12. Rod-shaped micropatterning enhances the electrophysiological maturation of cardiomyocytes derived from human induced pluripotent stem cells
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Al Sayed, Zeina R., Jouve, Charlène, Seguret, Magali, Ruiz-Velasco, Andrea, Pereira, Céline, Trégouët, David-Alexandre, and Hulot, Jean-Sébastien
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- 2024
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13. Plasma levels of complement components C5 and C9 are associated with thrombin generation
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Vacik Díaz, Rocío, Munsch, Gaëlle, Iglesias, Maria Jesus, Pallares Robles, Alejandro, Ibrahim-Kosta, Manal, Nourse, Jamie, Khan, Essak, Castoldi, Elisabetta, Saut, Noémie, Boland, Anne, Germain, Marine, Deleuze, Jean-François, Odeberg, Jacob, Morange, Pierre-Emmanuel, Danckwardt, Sven, Tregouët, David-Alexandre, and Goumidi, Louisa
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- 2024
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14. Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism
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Lindstrom, Sara, Wang, Lu, Smith, Erin, Gordon, William, Van Hylckama Vlieg, Astrid, De Andrade, Mariza, Brody, Jennifer, Pattee, Jack, Haessler, Jeffrey, Brumpton, Ben, Chasman, Daniel, Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri, MacDonald, James, Braekkan, Sigrid, Armasu, Sebastian, Pankratz, Nathan, Jackson, Rabecca, Nielsen, Jonas, Giulianini, Franco, Puurunen, Marja, Ibrahim, Manal, Heckbert, Susan, Bammler, Theo, Frazer, Kelly, McCauley, Bryan, Taylor, Kent, Pankow, James, Reiner, Alexander, Gabrielsen, Maiken, Deleuze, Jean-François, O'Donnell, Chris, Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits, Heit, John, Psaty, Bruce, Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul, Morange, Pierre-Emmanuel, Johnson, Andrew, Kabrhel, Christopher, Trégouët, David-Alexandre, Smith, Nicholas, Tan, Marcus C.B., Isom, Chelsea A., Liu, Yangzi, Wu, Lang, Zhou, Dan, and Gamazon, Eric R.
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- 2024
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15. Genome-wide investigation of exogenous female hormones, genetic variation, and venous thromboembolism risk
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Hasser, Emily K., Brody, Jennifer A., Bartz, Traci M., Thibord, Florian, Li-Gao, Ruifang, Kauko, Anni, Wiggins, Kerri L., Teder-Laving, Maris, Kim, Jihye, Munsch, Gaëlle, Haile, Helen G., Deleuze, Jean-Francois, van Hylckama Vlieg, Astrid, Wolberg, Alisa S., Boland, Anne, Morange, Pierre-Emmanuel, Kraft, Peter, Lowenstein, Charles J., Emmerich, Joseph, Sitlani, Colleen M., Suchon, Pierre, Rosendaal, Frits R., Niiranen, Teemu, Kabrhel, Christopher, Trégouët, David-Alexandre, and Smith, Nicholas L.
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- 2024
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16. Next-generation sequencing strategies in venous thromboembolism: in whom and for what purpose?
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Trégouët, David-Alexandre and Morange, Pierre-Emmanuel
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- 2024
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17. CAVIN1-Mediated hERG Dynamics: A Novel Mechanism Underlying the Interindividual Variability in Drug-Induced Long QT
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Al Sayed, Zeina R., Pereira, Céline, Le Borgne, Rémi, Viaris de Lesegno, Christine, Jouve, Charlène, Pénard, Esthel, Mallet, Adeline, Masurkar, Nihar, Loussouarn, Gildas, Verbavatz, Jean-Marc, Lamaze, Christophe, Trégouët, David-Alexandre, and Hulot, Jean-Sébastien
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- 2024
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18. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels
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Abe, Namiko, Abecasis, Gonçalo, Aguet, Francois, Albert, Christine, Almasy, Laura, Alonso, Alvaro, Ament, Seth, Anderson, Peter, Anugu, Pramod, Applebaum-Bowden, Deborah, Ardlie, Kristin, Arking, Dan, Arnett, Donna K, Ashley-Koch, Allison, Aslibekyan, Stella, Assimes, Tim, Auer, Paul, Avramopoulos, Dimitrios, Ayas, Najib, Balasubramanian, Adithya, Barnard, John, Barnes, Kathleen, Barr, R. Graham, Barron-Casella, Emily, Barwick, Lucas, Beaty, Terri, Beck, Gerald, Becker, Diane, Becker, Lewis, Beer, Rebecca, Beitelshees, Amber, Benjamin, Emelia, Benos, Takis, Bezerra, Marcos, Bielak, Larry, Bis, Joshua, Blackwell, Thomas, Blangero, John, Blue, Nathan, Boerwinkle, Eric, Bowden, Donald W., Bowler, Russell, Brody, Jennifer, Broeckel, Ulrich, Broome, Jai, Brown, Deborah, Bunting, Karen, Burchard, Esteban, Bustamante, Carlos, Buth, Erin, Cade, Brian, Cardwell, Jonathan, Carey, Vincent, Carrier, Julie, Carson, April P., Carty, Cara, Casaburi, Richard, Casas Romero, Juan P, Casella, James, Castaldi, Peter, Chaffin, Mark, Chang, Christy, Chang, Yi-Cheng, Chasman, Daniel, Chavan, Sameer, Chen, Bo-Juen, Chen, Wei-Min, Ida Chen, Yii-Der, Cho, Michael, Choi, Seung Hoan, Chuang, Lee-Ming, Chung, Mina, Chung, Ren-Hua, Clish, Clary, Comhair, Suzy, Conomos, Matthew, Cornell, Elaine, Correa, Adolfo, Crandall, Carolyn, Crapo, James, Cupples, L. Adrienne, Curran, Joanne, Curtis, Jeffrey, Custer, Brian, Damcott, Coleen, Darbar, Dawood, David, Sean, Davis, Colleen, Daya, Michelle, de Andrade, Mariza, de las Fuentes, Lisa, de Vries, Paul, DeBaun, Michael, Deka, Ranjan, DeMeo, Dawn, Devine, Scott, Dinh, Huyen, Doddapaneni, Harsha, Duan, Qing, Dugan-Perez, Shannon, Duggirala, Ravi, Durda, Jon Peter, Dutcher, Susan K., Eaton, Charles, Ekunwe, Lynette, El Boueiz, Adel, Ellinor, Patrick, Emery, Leslie, Erzurum, Serpil, Farber, Charles, Farek, Jesse, Fingerlin, Tasha, Flickinger, Matthew, Fornage, Myriam, Franceschini, Nora, Frazar, Chris, Fu, Mao, Fullerton, Stephanie M., Fulton, Lucinda, Gabriel, Stacey, Gan, Weiniu, Gao, Shanshan, Gao, Yan, Gass, Margery, Geiger, Heather, Gelb, Bruce, Geraci, Mark, Germer, Soren, Gerszten, Robert, Ghosh, Auyon, Gibbs, Richard, Gignoux, Chris, Gladwin, Mark, Glahn, David, Gogarten, Stephanie, Gong, Da-Wei, Goring, Harald, Graw, Sharon, Gray, Kathryn J., Grine, Daniel, Gross, Colin, Gu, C. Charles, Guan, Yue, Guo, Xiuqing, Gupta, Namrata, Haessler, Jeff, Hall, Michael, Han, Yi, Hanly, Patrick, Harris, Daniel, Hawley, Nicola L., He, Jiang, Heavner, Ben, Heckbert, Susan, Hernandez, Ryan, Herrington, David, Hersh, Craig, Hidalgo, Bertha, Hixson, James, Hobbs, Brian, Hokanson, John, Hong, Elliott, Hoth, Karin, Hsiung, Chao (Agnes), Hu, Jianhong, Hung, Yi-Jen, Huston, Haley, Hwu, Chii Min, Irvin, Marguerite Ryan, Jackson, Rebecca, Jain, Deepti, Jaquish, Cashell, Johnsen, Jill, Johnson, Andrew, Johnson, Craig, Johnston, Rich, Jones, Kimberly, Kang, Hyun Min, Kaplan, Robert, Kardia, Sharon, Kelly, Shannon, Kenny, Eimear, Kessler, Michael, Khan, Alyna, Khan, Ziad, Kim, Wonji, Kimoff, John, Kinney, Greg, Konkle, Barbara, Kooperberg, Charles, Kramer, Holly, Lange, Christoph, Lange, Ethan, Lange, Leslie, Laurie, Cathy, Laurie, Cecelia, LeBoff, Meryl, Lee, Jiwon, Lee, Sandra, Lee, Wen-Jane, LeFaive, Jonathon, Levine, David, Levy, Dan, Lewis, Joshua, Li, Xiaohui, Li, Yun, Lin, Henry, Lin, Honghuang, Lin, Xihong, Liu, Simin, Liu, Yongmei, Liu, Yu, Loos, Ruth J. F., Lubitz, Steven, Lunetta, Kathryn, Luo, James, Magalang, Ulysses, Mahaney, Michael, Make, Barry, Manichaikul, Ani, Manning, Alisa, Manson, JoAnn, Martin, Lisa, Marton, Melissa, Mathai, Susan, Mathias, Rasika, May, Susanne, McArdle, Patrick, McDonald, Merry-Lynn, McFarland, Sean, McGarvey, Stephen, McGoldrick, Daniel, McHugh, Caitlin, McNeil, Becky, Mei, Hao, Meigs, James, Menon, Vipin, Mestroni, Luisa, Metcalf, Ginger, Meyers, Deborah A, Mignot, Emmanuel, Mikulla, Julie, Min, Nancy, Minear, Mollie, Minster, Ryan L, Mitchell, Braxton D., Moll, Matt, Momin, Zeineen, Montasser, May E., Montgomery, Courtney, Muzny, Donna, Mychaleckyj, Josyf C, Nadkarni, Girish, Naik, Rakhi, Naseri, Take, Natarajan, Pradeep, Nekhai, Sergei, Nelson, Sarah C., Neltner, Bonnie, Nessner, Caitlin, Nickerson, Deborah, Nkechinyere, Osuji, North, Kari, O'Connell, Jeff, O'Connor, Tim, Ochs-Balcom, Heather, Okwuonu, Geoffrey, Pack, Allan, Paik, David T., Palmer, Nicholette, Pankow, James, Papanicolaou, George, Parker, Cora, Peloso, Gina, Peralta, Juan Manuel, Perez, Marco, Perry, James, Peters, Ulrike, Peyser, Patricia, Phillips, Lawrence S, Pleiness, Jacob, Pollin, Toni, Post, Wendy, Becker, Julia Powers, Boorgula, Meher Preethi, Preuss, Michael, Psaty, Bruce, Qasba, Pankaj, Qiao, Dandi, Qin, Zhaohui, Rafaels, Nicholas, Raffield, Laura, Rajendran, Mahitha, Ramachandran, Vasan S., Rao, D. C., Rasmussen-Torvik, Laura, Ratan, Aakrosh, Redline, Susan, Reed, Robert, Reeves, Catherine, Regan, Elizabeth, Reiner, Alex, Reupena, Muagututi‘a Sefuiva, Rice, Ken, Rich, Stephen, Robillard, Rebecca, Robine, Nicolas, Roden, Dan, Roselli, Carolina, Rotter, Jerome, Ruczinski, Ingo, Runnels, Alexi, Russell, Pamela, Ruuska, Sarah, Ryan, Kathleen, Sabino, Ester Cerdeira, Saleheen, Danish, Salimi, Shabnam, Salvi, Sejal, Salzberg, Steven, Sandow, Kevin, Sankaran, Vijay G., Santibanez, Jireh, Schwander, Karen, Schwartz, David, Sciurba, Frank, Seidman, Christine, Seidman, Jonathan, Sériès, Frédéric, Sheehan, Vivien, Sherman, Stephanie L., Shetty, Amol, Shetty, Aniket, Hui-Heng Sheu, Wayne, Shoemaker, M. Benjamin, Silver, Brian, Silverman, Edwin, Skomro, Robert, Smith, Albert Vernon, Smith, Jennifer, Smith, Josh, Smith, Nicholas, Smith, Tanja, Smoller, Sylvia, Snively, Beverly, Snyder, Michael, Sofer, Tamar, Sotoodehnia, Nona, Stilp, Adrienne M., Storm, Garrett, Streeten, Elizabeth, Su, Jessica Lasky, Sung, Yun Ju, Sylvia, Jody, Szpiro, Adam, Taliun, Daniel, Tang, Hua, Taub, Margaret, Taylor, Kent D., Taylor, Matthew, Taylor, Simeon, Telen, Marilyn, Thornton, Timothy A., Threlkeld, Machiko, Tinker, Lesley, Tirschwell, David, Tishkoff, Sarah, Tiwari, Hemant, Tong, Catherine, Tracy, Russell, Tsai, Michael, Vaidya, Dhananjay, Van Den Berg, David, VandeHaar, Peter, Vrieze, Scott, Walker, Tarik, Wallace, Robert, Walts, Avram, Wang, Fei Fei, Wang, Heming, Wang, Jiongming, Watson, Karol, Watt, Jennifer, Weeks, Daniel E., Weinstock, Joshua, Weir, Bruce, Weiss, Scott T, Weng, Lu-Chen, Wessel, Jennifer, Willer, Cristen, Williams, Kayleen, Williams, L. Keoki, Wilson, Carla, Wilson, James, Winterkorn, Lara, Wong, Quenna, Wu, Joseph, Xu, Huichun, Yanek, Lisa, Yang, Ivana, Yu, Ketian, Zekavat, Seyedeh Maryam, Zhang, Yingze, Zhao, Snow Xueyan, Zhao, Wei, Zhu, Xiaofeng, Ziv, Elad, Zody, Michael, Zoellner, Sebastian, Lindstrom, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rabecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, AlexandreTrégouët, David, Smith, Nicholas L., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc-Quynh, Bebo, Allison, Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Lewis, Joshua P., Rodriguez, Benjamin A. T., Polasek, Ozren, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David-Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Davies, Gail, Delgado, Graciela E., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., Osburn, William O., O'Connell, Jeffrey R., Beswick, Andrew, Kolcic, Ivana, Souto, Juan Carlos, Becker, Lewis C., Hansen, Torben, Doyle, Margaret F., Harris, Sarah E., Moissl, Angela P., Rich, Stephen S., Campbell, Harry, Stott, David J., Soria, Jose Manuel, de Maat, Moniek P. M., Brody, Lawrence C., Auer, Paul L., Ben-Shlomo, Yoav, Hayward, Caroline, Mathias, Rasika A., Kilpeläinen, Tuomas O., Lange, Leslie A., Cox, Simon R., März, Winfried, Rotter, Jerome I., Mook-Kanamori, Dennis O., Wilson, James F., van der Harst, Pim, Jukema, J. Wouter, Ikram, M. Arfan, Desch, Karl C., Sabater-Lleal, Maria, Lowenstein, Charles J., and Morrison, Alanna C.
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- 2024
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19. FGL1 as a modulator of plasma D‐dimer levels: Exome‐wide marker analysis of plasma tPA, PAI‐1, and D‐dimer
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Thibord, Florian, Song, Ci, Pattee, Jack, Rodriguez, Benjamin AT, Chen, Ming‐Huei, O’Donnell, Christopher J, Kleber, Marcus E, Delgado, Graciela E, Guo, Xiuqing, Yao, Jie, Taylor, Kent D, Ozel, Ayse Bilge, Brody, Jennifer A, McKnight, Barbara, Gyorgy, Beata, Simonsick, Eleanor, Leonard, Hampton L, Carrasquilla, Germán D, Guindo‐Martinez, Marta, Silveira, Angela, Temprano‐Sagrera, Gerard, Yanek, Lisa R, Becker, Diane M, Mathias, Rasika A, Becker, Lewis C, Raffield, Laura M, Kilpeläinen, Tuomas O, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Hamsten, Anders, Watkins, Hugh, Sabater‐Lleal, Maria, Nalls, Mike A, Trégouët, David‐Alexandre, Morange, Pierre‐Emmanuel, Psaty, Bruce M, Tracy, Russel P, Smith, Nicholas L, Desch, Karl C, Cushman, Mary, Rotter, Jerome I, de Vries, Paul S, Pankratz, Nathan D, Folsom, Aaron R, Morrison, Alanna C, März, Winfried, Tang, Weihong, and Johnson, Andrew D
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Human Genome ,Genetics ,Exome ,Fibrin Fibrinogen Degradation Products ,Fibrinogen ,Fibrinolysis ,Humans ,Plasminogen Activator Inhibitor 1 ,Tissue Plasminogen Activator ,computational biology ,exome ,fibrinogen ,fibrinolysis ,genetic association study ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundUse of targeted exome-arrays with common, rare variants and functionally enriched variation has led to discovery of new genes contributing to population variation in risk factors. Plasminogen activator-inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and the plasma product D-dimer are important components of the fibrinolytic system. There have been few large-scale genome-wide or exome-wide studies of PAI-1, tPA, and D-dimer.ObjectivesWe sought to discover new genetic loci contributing to variation in these traits using an exome-array approach.MethodsCohort-level analyses and fixed effects meta-analyses of PAI-1 (n = 15 603), tPA (n = 6876,) and D-dimer (n = 19 306) from 12 cohorts of European ancestry with diverse study design were conducted, including single-variant analyses and gene-based burden testing.ResultsFive variants located in NME7, FGL1, and the fibrinogen locus, all associated with D-dimer levels, achieved genome-wide significance (P
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- 2021
20. Single-Cell Study of Two Rat Models of Pulmonary Arterial Hypertension Reveals Connections to Human Pathobiology and Drug Repositioning.
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Hong, Jason, Arneson, Douglas, Umar, Soban, Ruffenach, Gregoire, Cunningham, Christine M, Ahn, In Sook, Diamante, Graciel, Bhetraratana, May, Park, John F, Said, Emma, Huynh, Caroline, Le, Trixie, Medzikovic, Lejla, Humbert, Marc, Soubrier, Florent, Montani, David, Girerd, Barbara, Trégouët, David-Alexandre, Channick, Richard, Saggar, Rajan, Eghbali, Mansoureh, and Yang, Xia
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Rare Diseases ,Genetics ,Lung ,2.1 Biological and endogenous factors ,Cardiovascular ,Animals ,Antihypertensive Agents ,Cells ,Cultured ,Disease Models ,Animal ,Drug Repositioning ,Gene Expression Regulation ,Humans ,Male ,Pulmonary Arterial Hypertension ,Rats ,Rats ,Sprague-Dawley ,pulmonary hypertension ,single-cell RNA sequencing ,drug repurposing ,monocrotaline ,Sugen-hypoxia ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
Rationale: The cellular and molecular landscape and translational value of commonly used models of pulmonary arterial hypertension (PAH) are poorly understood. Single-cell transcriptomics can enhance molecular understanding of preclinical models and facilitate their rational use and interpretation.Objectives: To determine and prioritize dysregulated genes, pathways, and cell types in lungs of PAH rat models to assess relevance to human PAH and identify drug repositioning candidates.Methods: Single-cell RNA sequencing was performed on the lungs of monocrotaline (MCT), Sugen-hypoxia (SuHx), and control rats to identify altered genes and cell types, followed by validation using flow-sorted cells, RNA in situ hybridization, and immunofluorescence. Relevance to human PAH was assessed by histology of lungs from patients and via integration with human PAH genetic loci and known disease genes. Candidate drugs were predicted using Connectivity Map.Measurements and Main Results: Distinct changes in genes and pathways in numerous cell types were identified in SuHx and MCT lungs. Widespread upregulation of NF-κB signaling and downregulation of IFN signaling was observed across cell types. SuHx nonclassical monocytes and MCT conventional dendritic cells showed particularly strong NF-κB pathway activation. Genes altered in SuHx nonclassical monocytes were significantly enriched for PAH-associated genes and genetic variants, and candidate drugs predicted to reverse the changes were identified. An open-access online platform was developed to share single-cell data and drug candidates (http://mergeomics.research.idre.ucla.edu/PVDSingleCell/).Conclusions: Our study revealed the distinct and shared dysregulation of genes and pathways in two commonly used PAH models for the first time at single-cell resolution and demonstrated their relevance to human PAH and utility for drug repositioning.
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- 2021
21. Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
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Duperron, Marie-Gabrielle, Knol, Maria J., Le Grand, Quentin, Evans, Tavia E., Mishra, Aniket, Tsuchida, Ami, Roshchupkin, Gennady, Konuma, Takahiro, Trégouët, David-Alexandre, Romero, Jose Rafael, Frenzel, Stefan, Luciano, Michelle, Hofer, Edith, Bourgey, Mathieu, Dueker, Nicole D., Delgado, Pilar, Hilal, Saima, Tankard, Rick M., Dubost, Florian, Shin, Jean, Saba, Yasaman, Armstrong, Nicola J., Bordes, Constance, Bastin, Mark E., Beiser, Alexa, Brodaty, Henry, Bülow, Robin, Carrera, Caty, Chen, Christopher, Cheng, Ching-Yu, Deary, Ian J., Gampawar, Piyush G., Himali, Jayandra J., Jiang, Jiyang, Kawaguchi, Takahisa, Li, Shuo, Macalli, Melissa, Marquis, Pascale, Morris, Zoe, Muñoz Maniega, Susana, Miyamoto, Susumu, Okawa, Masakazu, Paradise, Matthew, Parva, Pedram, Rundek, Tatjana, Sargurupremraj, Muralidharan, Schilling, Sabrina, Setoh, Kazuya, Soukarieh, Omar, Tabara, Yasuharu, Teumer, Alexander, Thalamuthu, Anbupalam, Trollor, Julian N., Valdés Hernández, Maria C., Vernooij, Meike W., Völker, Uwe, Wittfeld, Katharina, Wong, Tien Yin, Wright, Margaret J., Zhang, Junyi, Zhao, Wanting, Zhu, Yi-Cheng, Schmidt, Helena, Sachdev, Perminder S., Wen, Wei, Yoshida, Kazumichi, Joutel, Anne, Satizabal, Claudia L., Sacco, Ralph L., Bourque, Guillaume, Lathrop, Mark, Paus, Tomas, Fernandez-Cadenas, Israel, Yang, Qiong, Mazoyer, Bernard, Boutinaud, Philippe, Okada, Yukinori, Grabe, Hans J., Mather, Karen A., Schmidt, Reinhold, Joliot, Marc, Ikram, M. Arfan, Matsuda, Fumihiko, Tzourio, Christophe, Wardlaw, Joanna M., Seshadri, Sudha, Adams, Hieab H. H., and Debette, Stéphanie
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- 2023
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22. Genome-wide analysis identifies novel susceptibility loci for myocardial infarction
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Hartiala, Jaana A, Han, Yi, Jia, Qiong, Hilser, James R, Huang, Pin, Gukasyan, Janet, Schwartzman, William S, Cai, Zhiheng, Biswas, Subarna, Trégouët, David-Alexandre, Smith, Nicholas L, Consortium, The INVENT, Group, The CHARGE Consortium Hemostasis Working, Consortium, The GENIUS-CHD, Seldin, Marcus, Pan, Calvin, Mehrabian, Margarete, Lusis, Aldons J, Bazeley, Peter, Sun, Yan V, Liu, Chang, Quyyumi, Arshed A, Scholz, Markus, Thiery, Joachim, Delgado, Graciela E, Kleber, Marcus E, März, Winfried, Howe, Laurence J, Asselbergs, Folkert W, van Vugt, Marion, Vlachojannis, Georgios J, Patel, Riyaz S, Lyytikäinen, Leo-Pekka, Kähönen, Mika, Lehtimäki, Terho, Nieminen, Tuomo VM, Kuukasjärvi, Pekka, Laurikka, Jari O, Chang, Xuling, Heng, Chew-Kiat, Jiang, Rong, Kraus, William E, Hauser, Elizabeth R, Ferguson, Jane F, Reilly, Muredach P, Ito, Kaoru, Koyama, Satoshi, Kamatani, Yoichiro, Komuro, Issei, Japan, Biobank, Stolze, Lindsey K, Romanoski, Casey E, Khan, Mohammad Daud, Turner, Adam W, Miller, Clint L, Aherrahrou, Redouane, Civelek, Mete, Ma, Lijiang, Björkegren, Johan LM, Kumar, S Ram, Tang, WH Wilson, Hazen, Stanley L, and Allayee, Hooman
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Cardiovascular ,Heart Disease ,Clinical Research ,Heart Disease - Coronary Heart Disease ,Human Genome ,Genetics ,Aging ,Atherosclerosis ,Aetiology ,2.1 Biological and endogenous factors ,Coronary Artery Disease ,Endothelial Cells ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Japan ,Myocardial Infarction ,Polymorphism ,Single Nucleotide ,Risk Factors ,Myocardial infarction ,Genetic factors ,Genome-wide association study ,Meta-analysis ,SLC44A3 ,INVENT Consortium ,CHARGE Consortium Hemostasis Working Group ,GENIUS-CHD Consortium ,Biobank Japan ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
AimsWhile most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.Methods and resultsWe carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.ConclusionsA large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
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- 2021
23. Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
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Iglesias, Maria Jesus, Sanchez-Rivera, Laura, Ibrahim-Kosta, Manal, Naudin, Clément, Munsch, Gaëlle, Goumidi, Louisa, Farm, Maria, Smith, Philip M., Thibord, Florian, Kral-Pointner, Julia Barbara, Hong, Mun-Gwan, Suchon, Pierre, Germain, Marine, Schrottmaier, Waltraud, Dusart, Philip, Boland, Anne, Kotol, David, Edfors, Fredrik, Koprulu, Mine, Pietzner, Maik, Langenberg, Claudia, Damrauer, Scott M., Johnson, Andrew D., Klarin, Derek M., Smith, Nicholas L., Smadja, David M., Holmström, Margareta, Magnusson, Maria, Silveira, Angela, Uhlén, Mathias, Renné, Thomas, Martinez-Perez, Angel, Emmerich, Joseph, Deleuze, Jean-Francois, Antovic, Jovan, Soria Fernandez, Jose Manuel, Assinger, Alice, Schwenk, Jochen M., Souto Andres, Joan Carles, Morange, Pierre-Emmanuel, Butler, Lynn Marie, Trégouët, David-Alexandre, and Odeberg, Jacob
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- 2023
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24. Author Correction: Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
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Iglesias, Maria Jesus, Sanchez-Rivera, Laura, Ibrahim-Kosta, Manal, Naudin, Clément, Munsch, Gaëlle, Goumidi, Louisa, Farm, Maria, Smith, Philip M., Thibord, Florian, Kral-Pointner, Julia Barbara, Hong, Mun-Gwan, Suchon, Pierre, Germain, Marine, Schrottmaier, Waltraud, Dusart, Philip, Boland, Anne, Kotol, David, Edfors, Fredrik, Koprulu, Mine, Pietzner, Maik, Langenberg, Claudia, Damrauer, Scott M., Johnson, Andrew D., Klarin, Derek M., Smith, Nicholas L., Smadja, David M., Holmström, Margareta, Magnusson, Maria, Silveira, Angela, Uhlén, Mathias, Renné, Thomas, Martinez-Perez, Angel, Emmerich, Joseph, Deleuze, Jean-Francois, Antovic, Jovan, Soria Fernandez, Jose Manuel, Assinger, Alice, Schwenk, Jochen M., Souto Andres, Joan Carles, Morange, Pierre-Emmanuel, Butler, Lynn Marie, Trégouët, David-Alexandre, and Odeberg, Jacob
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- 2023
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25. uAUG creating variants in the 5’UTR of ENG causing Hereditary Hemorrhagic Telangiectasia
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Soukarieh, Omar, Tillet, Emmanuelle, Proust, Carole, Dupont, Charlène, Jaspard-Vinassa, Béatrice, Soubrier, Florent, Goyenvalle, Aurélie, Eyries, Mélanie, and Trégouët, David-Alexandre
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- 2023
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26. Association of ABO blood groups with venous thrombosis recurrence in middle-aged patients: insights from a weighted Cox analysis dedicated to ambispective design
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Munsch, Gaëlle, Goumidi, Louisa, van Hylckama Vlieg, Astrid, Ibrahim-Kosta, Manal, Bruzelius, Maria, Deleuze, Jean-François, Rosendaal, Frits R., Jacqmin-Gadda, Hélène, Morange, Pierre-Emmanuel, and Trégouët, David-Alexandre
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- 2023
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27. Cerebral small vessel disease genomics and its implications across the lifespan.
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Sargurupremraj, Muralidharan, Suzuki, Hideaki, Jian, Xueqiu, Sarnowski, Chloé, Evans, Tavia E, Bis, Joshua C, Eiriksdottir, Gudny, Sakaue, Saori, Terzikhan, Natalie, Habes, Mohamad, Zhao, Wei, Armstrong, Nicola J, Hofer, Edith, Yanek, Lisa R, Hagenaars, Saskia P, Kumar, Rajan B, van den Akker, Erik B, McWhirter, Rebekah E, Trompet, Stella, Mishra, Aniket, Saba, Yasaman, Satizabal, Claudia L, Beaudet, Gregory, Petit, Laurent, Tsuchida, Ami, Zago, Laure, Schilling, Sabrina, Sigurdsson, Sigurdur, Gottesman, Rebecca F, Lewis, Cora E, Aggarwal, Neelum T, Lopez, Oscar L, Smith, Jennifer A, Valdés Hernández, Maria C, van der Grond, Jeroen, Wright, Margaret J, Knol, Maria J, Dörr, Marcus, Thomson, Russell J, Bordes, Constance, Le Grand, Quentin, Duperron, Marie-Gabrielle, Smith, Albert V, Knopman, David S, Schreiner, Pamela J, Evans, Denis A, Rotter, Jerome I, Beiser, Alexa S, Maniega, Susana Muñoz, Beekman, Marian, Trollor, Julian, Stott, David J, Vernooij, Meike W, Wittfeld, Katharina, Niessen, Wiro J, Soumaré, Aicha, Boerwinkle, Eric, Sidney, Stephen, Turner, Stephen T, Davies, Gail, Thalamuthu, Anbupalam, Völker, Uwe, van Buchem, Mark A, Bryan, R Nick, Dupuis, Josée, Bastin, Mark E, Ames, David, Teumer, Alexander, Amouyel, Philippe, Kwok, John B, Bülow, Robin, Deary, Ian J, Schofield, Peter R, Brodaty, Henry, Jiang, Jiyang, Tabara, Yasuharu, Setoh, Kazuya, Miyamoto, Susumu, Yoshida, Kazumichi, Nagata, Manabu, Kamatani, Yoichiro, Matsuda, Fumihiko, Psaty, Bruce M, Bennett, David A, De Jager, Philip L, Mosley, Thomas H, Sachdev, Perminder S, Schmidt, Reinhold, Warren, Helen R, Evangelou, Evangelos, Trégouët, David-Alexandre, International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium (IHGC), Ikram, Mohammad A, Wen, Wei, DeCarli, Charles, Srikanth, Velandai K, Jukema, J Wouter, Slagboom, Eline P, and Kardia, Sharon LR
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International Network against Thrombosis (INVENT) Consortium ,International Headache Genomics Consortium ,Humans ,Alzheimer Disease ,Hypertension ,Medical History Taking ,Risk Assessment ,Risk Factors ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Stroke ,Genome-Wide Association Study ,Young Adult ,Diffusion Tensor Imaging ,Genetic Loci ,Mendelian Randomization Analysis ,Cerebral Small Vessel Diseases ,White Matter ,and over - Abstract
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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- 2020
28. Polygenic risk of major depressive disorder as a risk factor for venous thromboembolism
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Ward, Joey, Le, Ngoc-Quynh, Suryakant, Suryakant, Brody, Jennifer A., Amouyel, Philippe, Boland, Anne, Bown, Rosemary, Cullen, Breda, Debette, Stéphanie, Deleuze, Jean-François, Emmerich, Joseph, Graham, Nicholas, Germain, Marine, Anderson, Jana J., Pell, Jill P., Lyall, Donald M., Lyall, Laura M., Smith, Daniel J., Wiggins, Kerri L., Soria, José Manuel, Souto, Juan Carlos, Morange, Pierre-Emmanuel, Smith, Nicholas L., Trégouët, David-Alexandre, Sabater-Lleal, Maria, and Strawbridge, Rona J.
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- 2023
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29. Stroke genetics informs drug discovery and risk prediction across ancestries
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Mishra, Aniket, Malik, Rainer, Hachiya, Tsuyoshi, Jürgenson, Tuuli, Namba, Shinichi, Posner, Daniel C., Kamanu, Frederick K., Koido, Masaru, Le Grand, Quentin, Shi, Mingyang, He, Yunye, Georgakis, Marios K., Caro, Ilana, Krebs, Kristi, Liaw, Yi-Ching, Vaura, Felix C., Lin, Kuang, Winsvold, Bendik Slagsvold, Srinivasasainagendra, Vinodh, Parodi, Livia, Bae, Hee-Joon, Chauhan, Ganesh, Chong, Michael R., Tomppo, Liisa, Akinyemi, Rufus, Roshchupkin, Gennady V., Habib, Naomi, Jee, Yon Ho, Thomassen, Jesper Qvist, Abedi, Vida, Cárcel-Márquez, Jara, Nygaard, Marianne, Leonard, Hampton L., Yang, Chaojie, Yonova-Doing, Ekaterina, Knol, Maria J., Lewis, Adam J., Judy, Renae L., Ago, Tetsuro, Amouyel, Philippe, Armstrong, Nicole D., Bakker, Mark K., Bartz, Traci M., Bennett, David A., Bis, Joshua C., Bordes, Constance, Børte, Sigrid, Cain, Anael, Ridker, Paul M., Cho, Kelly, Chen, Zhengming, Cruchaga, Carlos, Cole, John W., de Jager, Phil L., de Cid, Rafael, Endres, Matthias, Ferreira, Leslie E., Geerlings, Mirjam I., Gasca, Natalie C., Gudnason, Vilmundur, Hata, Jun, He, Jing, Heath, Alicia K., Ho, Yuk-Lam, Havulinna, Aki S., Hopewell, Jemma C., Hyacinth, Hyacinth I., Inouye, Michael, Jacob, Mina A., Jeon, Christina E., Jern, Christina, Kamouchi, Masahiro, Keene, Keith L., Kitazono, Takanari, Kittner, Steven J., Konuma, Takahiro, Kumar, Amit, Lacaze, Paul, Launer, Lenore J., Lee, Keon-Joo, Lepik, Kaido, Li, Jiang, Li, Liming, Manichaikul, Ani, Markus, Hugh S., Marston, Nicholas A., Meitinger, Thomas, Mitchell, Braxton D., Montellano, Felipe A., Morisaki, Takayuki, Mosley, Thomas H., Nalls, Mike A., Nordestgaard, Børge G., O’Donnell, Martin J., Okada, Yukinori, Onland-Moret, N. Charlotte, Ovbiagele, Bruce, Peters, Annette, Psaty, Bruce M., Rich, Stephen S., Rosand, Jonathan, Sabatine, Marc S., Sacco, Ralph L., Saleheen, Danish, Sandset, Else Charlotte, Salomaa, Veikko, Sargurupremraj, Muralidharan, Sasaki, Makoto, Satizabal, Claudia L., Schmidt, Carsten O., Shimizu, Atsushi, Smith, Nicholas L., Sloane, Kelly L., Sutoh, Yoichi, Sun, Yan V., Tanno, Kozo, Tiedt, Steffen, Tatlisumak, Turgut, Torres-Aguila, Nuria P., Tiwari, Hemant K., Trégouët, David-Alexandre, Trompet, Stella, Tuladhar, Anil Man, Tybjærg-Hansen, Anne, van Vugt, Marion, Vibo, Riina, Verma, Shefali S., Wiggins, Kerri L., Wennberg, Patrik, Woo, Daniel, Wilson, Peter W. F., Xu, Huichun, Yang, Qiong, Yoon, Kyungheon, Millwood, Iona Y., Gieger, Christian, Ninomiya, Toshiharu, Grabe, Hans J., Jukema, J. Wouter, Rissanen, Ina L., Strbian, Daniel, Kim, Young Jin, Chen, Pei-Hsin, Mayerhofer, Ernst, Howson, Joanna M. M., Irvin, Marguerite R., Adams, Hieab, Wassertheil-Smoller, Sylvia, Christensen, Kaare, Ikram, Mohammad A., Rundek, Tatjana, Worrall, Bradford B., Lathrop, G. Mark, Riaz, Moeen, Simonsick, Eleanor M., Kõrv, Janika, França, Paulo H. C., Zand, Ramin, Prasad, Kameshwar, Frikke-Schmidt, Ruth, de Leeuw, Frank-Erik, Liman, Thomas, Haeusler, Karl Georg, Ruigrok, Ynte M., Heuschmann, Peter Ulrich, Longstreth, W. T., Jung, Keum Ji, Bastarache, Lisa, Paré, Guillaume, Damrauer, Scott M., Chasman, Daniel I., Rotter, Jerome I., Anderson, Christopher D., Zwart, John-Anker, Niiranen, Teemu J., Fornage, Myriam, Liaw, Yung-Po, Seshadri, Sudha, Fernández-Cadenas, Israel, Walters, Robin G., Ruff, Christian T., Owolabi, Mayowa O., Huffman, Jennifer E., Milani, Lili, Kamatani, Yoichiro, Dichgans, Martin, and Debette, Stephanie
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- 2022
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30. Antithrombin, PC (Protein C), and PS (Protein S): Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels
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Ji, Yuekai, Temprano-Sagrera, Gerard, Holle, Lori A., Bebo, Allison, Brody, Jennifer, Le, Ngoc-Quynh, Kangro, Kadri, Brown, Michael R., Martinez-Perez, Angel, Sitlani, Colleen M., Suchon, Pierre, Kleber, Marcus E., Emmert, David B., Bilge Ozel, Ayse, Dobson, Dre’Von A., Tang, Weihong, Llobet, Dolors, Tracy, Russell P., Deleuze, Jean-François, Delgado, Graciela E., Gögele, Martin, Wiggins, Kerri L., Souto, Juan Carlos, Pankow, James S., Taylor, Kent D., Trégouët, David-Alexandre, Moissl, Angela P., Fuchsberger, Christian, Rosendaal, Frits R., Morrison, Alanna C., Soria, Jose Manuel, Cushman, Mary, Morange, Pierre-Emmanuel, März, Winfried, Hicks, Andrew A., Desch, Karl C., Johnson, Andrew D., de Vries, Paul S., Wolberg, Alisa S., Smith, Nicholas L., and Sabater-Lleal, Maria
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- 2023
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31. Two SERPINC1 variants affecting N-glycosylation of Asn224 cause severe thrombophilia not detected by functional assays
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de la Morena-Barrio, Maria Eugenia, Suchon, Pierre, Jacobsen, Eva Marie, Iversen, Nina, Miñano, Antonia, de la Morena-Barrio, Belén, Bravo-Pérez, Carlos, Padilla, Jose, Cifuentes, Rosa, Asenjo, Susana, Deleuze, Jean François, Trégouët, David Alexandre, Lozano, Maria Luisa, Vicente, Vicente, Sandset, Per Morten, Morange, Pierre Emmanuel, and Corral, Javier
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- 2022
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32. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations
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Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, 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 HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, 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, 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, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, 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 LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, 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 MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin
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- 2022
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33. Antithrombin, Protein C, and Protein S: Genome and Transcriptome-Wide Association Studies Identify 7 Novel Loci Regulating Plasma Levels
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Ji, Yuekai, Temprano-Sagrera, Gerard, Holle, Lori A., Bebo, Allison, Brody, Jennifer A., Le, Ngoc-Quynh, Kangro, Kadri, Brown, Michael R., Martinez-Perez, Angel, Sitlani, Colleen M., Suchon, Pierre, Kleber, Marcus E., Emmert, David B., Bilge Ozel, Ayse, Dobson, Dre’Von A., Tang, Weihong, Llobet, Dolors, Tracy, Russell P., Deleuze, Jean-François, Delgado, Graciela E., Gögele, Martin, Wiggins, Kerri L., Souto, Juan Carlos, Pankow, James S., Taylor, Kent D., Trégouët, David-Alexandre, Moissl, Angela P., Fuchsberger, Christian, Rosendaal, Frits R., Morrison, Alanna C., Soria, Jose Manuel, Cushman, Mary, Morange, Pierre-Emmanuel, März, Winfried, Hicks, Andrew A., Desch, Karl C., Johnson, Andrew D., de Vries, Paul S., Wolberg, Alisa S., Smith, Nicholas L., and Sabater-Lleal, Maria
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- 2023
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34. Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels
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Sabater-Lleal, Maria, Huffman, Jennifer E, de Vries, Paul S, Marten, Jonathan, Mastrangelo, Michael A, Song, Ci, Pankratz, Nathan, Ward-Caviness, Cavin K, Yanek, Lisa R, Trompet, Stella, Delgado, Graciela E, Guo, Xiuqing, Bartz, Traci M, Martinez-Perez, Angel, Germain, Marine, de Haan, Hugoline G, Ozel, Ayse B, Polasek, Ozren, Smith, Albert V, Eicher, John D, Reiner, Alex P, Tang, Weihong, Davies, Neil M, Stott, David J, Rotter, Jerome I, Tofler, Geoffrey H, Boerwinkle, Eric, de Maat, Moniek PM, Kleber, Marcus E, Welsh, Paul, Brody, Jennifer A, Chen, Ming-Huei, Vaidya, Dhananjay, Soria, José Manuel, Suchon, Pierre, van Hylckama Vlieg, Astrid, Desch, Karl C, Kolcic, Ivana, Joshi, Peter K, Launer, Lenore J, Harris, Tamara B, Campbell, Harry, Rudan, Igor, Becker, Diane M, Li, Jun Z, Rivadeneira, Fernando, Uitterlinden, André G, Hofman, Albert, Franco, Oscar H, Cushman, Mary, Psaty, Bruce M, Morange, Pierre-Emmanuel, McKnight, Barbara, Chong, Michael R, Fernandez-Cadenas, Israel, Rosand, Jonathan, Lindgren, Arne, Consortium, INVENT Consortium MEGASTROKE Consortium of the International Stroke Genetics, Gudnason, Vilmundur, Wilson, James F, Hayward, Caroline, Ginsburg, David, Fornage, Myriam, Rosendaal, Frits R, Souto, Juan Carlos, Becker, Lewis C, Jenny, Nancy S, März, Winfried, Jukema, J Wouter, Dehghan, Abbas, Trégouët, David-Alexandre, Morrison, Alanna C, Johnson, Andrew D, O’Donnell, Christopher J, Strachan, David P, Lowenstein, Charles J, and Smith, Nicholas L
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Epidemiology ,Health Sciences ,Human Genome ,Hematology ,Genetics ,Clinical Research ,Atherosclerosis ,Biotechnology ,2.1 Biological and endogenous factors ,Cardiovascular ,Blood ,Arterial Occlusive Diseases ,Biomarkers ,Blood Coagulation ,Blood Coagulation Disorders ,Inherited ,Factor VIII ,Genetic Loci ,Genetic Markers ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Mendelian Randomization Analysis ,Phenotype ,Ribosomal Protein L3 ,Risk Factors ,Venous Thrombosis ,von Willebrand Factor ,cardiovascular diseases ,factor VIII ,genome-wide association studies ,genetics ,risk factors ,von Willebrand factor ,INVENT Consortium ,MEGASTROKE Consortium of the International Stroke Genetics Consortium ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences ,Sports science and exercise - Abstract
BackgroundFactor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF.MethodsWe meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated ≈35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events.ResultsWe identified 13 novel genome-wide significant ( P≤2.5×10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk.ConclusionsThe meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events.
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- 2019
35. Explainable Artificial Neural Network for Recurrent Venous Thromboembolism Based on Plasma Proteomics
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Razzaq, Misbah, Goumidi, Louisa, Iglesias, Maria-Jesus, Munsch, Gaëlle, Bruzelius, Maria, Ibrahim-Kosta, Manal, Butler, Lynn, Odeberg, Jacob, Morange, Pierre-Emmanuel, Tregouet, David Alexandre, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Cinquemani, Eugenio, editor, and Paulevé, Loïc, editor
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- 2021
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36. Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation
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Goumidi, Louisa, Thibord, Florian, Wiggins, Kerri L., Li-Gao, Ruifang, Brown, Mickael R., van Hylckama Vlieg, Astrid, Souto, Joan-Carles, Soria, José-Manuel, Ibrahim-Kosta, Manal, Saut, Noémie, Daian, Delphine, Olaso, Robert, Amouyel, Philippe, Debette, Stéphanie, Boland, Anne, Bailly, Pascal, Morrison, Alanna C., Mook-Kanamori, Denis O., Deleuze, Jean-François, Johnson, Andrew, de Vries, Paul S., Sabater-Lleal, Maria, Chiaroni, Jacques, Smith, Nicholas L., Rosendaal, Frits R., Chasman, Daniel I., Trégouët, David-Alexandre, and Morange, Pierre-Emmanuel
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- 2021
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37. Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies.
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Fawaz, Sami, Marti, Severine, Dufossee, Melody, Pucheu, Yann, Gaufroy, Astrid, Broitman, Jean, Bidet, Audrey, Soumare, Aicha, Munsch, Gaëlle, Tzourio, Christophe, Debette, Stephanie, Trégouët, David-Alexandre, James, Chloe, Mansier, Olivier, and Couffinhal, Thierry
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- 2024
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38. ABO blood group, glycosyltransferase activity and risk of venous thromboembolism
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Ibrahim-Kosta, Manal, Bailly, Pascal, Silvy, Monique, Saut, Noemie, Suchon, Pierre, Morange, Pierre-Emmanuel, Chiaroni, Jacques, Trégouët, David-Alexandre, and Goumidi, Louisa
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- 2020
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39. A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling
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Rodriguez, Benjamin A.T., Bhan, Arunoday, Beswick, Andrew, Elwood, Peter C., Niiranen, Teemu J., Salomaa, Veikko, Trégouët, David-Alexandre, Morange, Pierre-Emmanuel, Civelek, Mete, Ben-Shlomo, Yoav, Schlaeger, Thorsten, Chen, Ming-Huei, and Johnson, Andrew D.
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- 2020
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40. Whole-exome sequencing identifies rare variants in STAB2 associated with venous thromboembolic disease
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Desch, Karl C., Ozel, Ayse B., Halvorsen, Matt, Jacobi, Paula M., Golden, Krista, Underwood, Mary, Germain, Marine, Tregouet, David-Alexandre, Reitsma, Pieter H., Kearon, Clive, Mokry, Lauren, Richards, J. Brent, Williams, Frances, Li, Jun Z., Goldstein, David, and Ginsburg, David
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- 2020
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41. Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States
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Shu, Le, Chan, Kei Hang K, Zhang, Guanglin, Huan, Tianxiao, Kurt, Zeyneb, Zhao, Yuqi, Codoni, Veronica, Trégouët, David-Alexandre, Consortium, Cardiogenics, Yang, Jun, Wilson, James G, Luo, Xi, Levy, Daniel, Lusis, Aldons J, Liu, Simin, and Yang, Xia
- Subjects
Biological Sciences ,Genetics ,Heart Disease ,Diabetes ,Human Genome ,Cardiovascular ,Biotechnology ,2.1 Biological and endogenous factors ,Metabolic and endocrine ,Good Health and Well Being ,Adipocytes ,Amino Acids ,Branched-Chain ,Animals ,Cardiovascular Diseases ,Caveolin 1 ,Diabetes Mellitus ,Type 2 ,Disease Models ,Animal ,Ethnicity ,Extracellular Matrix Proteins ,Gene Expression Regulation ,Gene Regulatory Networks ,Genome-Wide Association Study ,Glucose ,Glycoproteins ,Humans ,Hydroxymethylglutaryl CoA Reductases ,Insulin-Like Growth Factor I ,Lipid Metabolism ,Male ,Mice ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Reproducibility of Results ,United States ,Cardiogenics Consortium ,Developmental Biology - Abstract
Cardiovascular diseases (CVD) and type 2 diabetes (T2D) are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought to identify the shared gene networks and their key intervening drivers for both CVD and T2D by conducting a comprehensive integrative analysis driven by five multi-ethnic genome-wide association studies (GWAS) for CVD and T2D, expression quantitative trait loci (eQTLs), ENCODE, and tissue-specific gene network models (both co-expression and graphical models) from CVD and T2D relevant tissues. We identified pathways regulating the metabolism of lipids, glucose, and branched-chain amino acids, along with those governing oxidation, extracellular matrix, immune response, and neuronal system as shared pathogenic processes for both diseases. Further, we uncovered 15 key drivers including HMGCR, CAV1, IGF1 and PCOLCE, whose network neighbors collectively account for approximately 35% of known GWAS hits for CVD and 22% for T2D. Finally, we cross-validated the regulatory role of the top key drivers using in vitro siRNA knockdown, in vivo gene knockout, and two Hybrid Mouse Diversity Panels each comprised of >100 strains. Findings from this in-depth assessment of genetic and functional data from multiple human cohorts provide strong support that common sets of tissue-specific molecular networks drive the pathogenesis of both CVD and T2D across ethnicities and help prioritize new therapeutic avenues for both CVD and T2D.
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- 2017
42. Association of LIfestyle for BRAin health risk score (LIBRA) and genetic susceptibility with incident dementia and cognitive decline
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Neuffer, Jeanne, primary, Wagner, Maude, additional, Moreno, Elisa, additional, Grand, Quentin Le, additional, Mishra, Aniket, additional, Trégouët, David‐Alexandre, additional, Leffondre, Karen, additional, Proust‐Lima, Cécile, additional, Foubert‐Samier, Alexandra, additional, Berr, Claudine, additional, Tzourio, Christophe, additional, Helmer, Catherine, additional, Debette, Stéphanie, additional, and Samieri, Cécilia, additional
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- 2024
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43. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration
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de Vries, Paul S, Chasman, Daniel I, Sabater-Lleal, Maria, Chen, Ming-Huei, Huffman, Jennifer E, Steri, Maristella, Tang, Weihong, Teumer, Alexander, Marioni, Riccardo E, Grossmann, Vera, Hottenga, Jouke J, Trompet, Stella, Müller-Nurasyid, Martina, Zhao, Jing Hua, Brody, Jennifer A, Kleber, Marcus E, Guo, Xiuqing, Wang, Jie Jin, Auer, Paul L, Attia, John R, Yanek, Lisa R, Ahluwalia, Tarunveer S, Lahti, Jari, Venturini, Cristina, Tanaka, Toshiko, Bielak, Lawrence F, Joshi, Peter K, Rocanin-Arjo, Ares, Kolcic, Ivana, Navarro, Pau, Rose, Lynda M, Oldmeadow, Christopher, Riess, Helene, Mazur, Johanna, Basu, Saonli, Goel, Anuj, Yang, Qiong, Ghanbari, Mohsen, Willemsen, Gonneke, Rumley, Ann, Fiorillo, Edoardo, de Craen, Anton JM, Grotevendt, Anne, Scott, Robert, Taylor, Kent D, Delgado, Graciela E, Yao, Jie, Kifley, Annette, Kooperberg, Charles, Qayyum, Rehan, Lopez, Lorna M, Berentzen, Tina L, Räikkönen, Katri, Mangino, Massimo, Bandinelli, Stefania, Peyser, Patricia A, Wild, Sarah, Trégouët, David-Alexandre, Wright, Alan F, Marten, Jonathan, Zemunik, Tatijana, Morrison, Alanna C, Sennblad, Bengt, Tofler, Geoffrey, de Maat, Moniek PM, de Geus, Eco JC, Lowe, Gordon D, Zoledziewska, Magdalena, Sattar, Naveed, Binder, Harald, Völker, Uwe, Waldenberger, Melanie, Khaw, Kay-Tee, Mcknight, Barbara, Huang, Jie, Jenny, Nancy S, Holliday, Elizabeth G, Qi, Lihong, Mcevoy, Mark G, Becker, Diane M, Starr, John M, Sarin, Antti-Pekka, Hysi, Pirro G, Hernandez, Dena G, Jhun, Min A, Campbell, Harry, Hamsten, Anders, Rivadeneira, Fernando, Mcardle, Wendy L, Slagboom, P Eline, Zeller, Tanja, Koenig, Wolfgang, Psaty, Bruce M, Haritunians, Talin, Liu, Jingmin, Palotie, Aarno, Uitterlinden, André G, Stott, David J, Hofman, Albert, and Franco, Oscar H
- Subjects
Biological Sciences ,Genetics ,Human Genome ,2.1 Biological and endogenous factors ,Adult ,Aged ,Aged ,80 and over ,Female ,Fibrinogen ,Genetic Loci ,Genome-Wide Association Study ,Humans ,INDEL Mutation ,Male ,Middle Aged ,Polymorphism ,Single Nucleotide ,White People ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.
- Published
- 2016
44. Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy
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Zheng, Sean L, Henry, Albert, Cannie, Douglas, Lee, Michael, Miller, David, McGurk, Kathryn A, Bond, Isabelle, Xu, Xiao, Issa, Hanane, Francis, Catherine, De Marvao, Antonio, Theotokis, Pantazis I, Buchan, Rachel J, Speed, Doug, Abner, Erik, Adams, Lance, Aragam, Krishna G, Ärnlöv, Johan, Raja, Anna Axelsson, Backman, Joshua D, Baksi, John, Barton, Paul J R, Biddinger, Kiran J, Boersma, Eric, Brandimarto, Jeffrey, Brunak, Søren, Bundgaard, Henning, Carey, David J, Charron, Philippe, Cook, James P, Cook, Stuart A, Denaxas, Spiros, Deleuze, Jean-François, Doney, Alexander S, Elliott, Perry, Erikstrup, Christian, Esko, Tõnu, Farber-Eger, Eric H, Finan, Chris, Garnier, Sophie, Ghouse, Jonas, Giedraitis, Vilmantas, Guðbjartsson, Daniel F, Haggerty, Christopher M, Halliday, Brian P, Helgadottir, Anna, Hemingway, Harry, Hillege, Hans L, Kardys, Isabella, Lind, Lars, Lindgren, Cecilia M, Lowery, Brandon D, Manisty, Charlotte, Margulies, Kenneth B, Moon, James C, Mordi, Ify R, Morley, Michael P, Morris, Andrew D, Morris, Andrew P, Morton, Lori, Noursadeghi, Mahdad, Ostrowski, Sisse R, Owens, Anjali T, Palmer, Colin N A, Pantazis, Antonis, Pedersen, Ole B V, Prasad, Sanjay K, Shekhar, Akshay, Smelser, Diane T, Srinivasan, Sundararajan, Stefansson, Kari, Sveinbjörnsson, Garðar, Syrris, Petros, Tammesoo, Mari-Liis, Tayal, Upasana, Teder-Laving, Maris, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Tragante, Vinicius, Trégouët, David-Alexandre, Treibel, Thomas A, Ullum, Henrik, Valdes, Ana M, van Setten, Jessica, van Vugt, Marion, Veluchamy, Abirami, Verschuren, W M Monique, Villard, Eric, Yang, Yifan, Asselbergs, Folkert W, Cappola, Thomas P, Dube, Marie-Pierre, Dunn, Michael E, Ellinor, Patrick T, Hingorani, Aroon D, Lang, Chim C, Samani, Nilesh J, Shah, Svati H, Smith, J Gustav, Vasan, Ramachandran S, O'Regan, Declan P, Holm, Hilma, Noseda, Michela, Wells, Quinn, Ware, James S, Lumbers, R Thomas, Zheng, Sean L, Henry, Albert, Cannie, Douglas, Lee, Michael, Miller, David, McGurk, Kathryn A, Bond, Isabelle, Xu, Xiao, Issa, Hanane, Francis, Catherine, De Marvao, Antonio, Theotokis, Pantazis I, Buchan, Rachel J, Speed, Doug, Abner, Erik, Adams, Lance, Aragam, Krishna G, Ärnlöv, Johan, Raja, Anna Axelsson, Backman, Joshua D, Baksi, John, Barton, Paul J R, Biddinger, Kiran J, Boersma, Eric, Brandimarto, Jeffrey, Brunak, Søren, Bundgaard, Henning, Carey, David J, Charron, Philippe, Cook, James P, Cook, Stuart A, Denaxas, Spiros, Deleuze, Jean-François, Doney, Alexander S, Elliott, Perry, Erikstrup, Christian, Esko, Tõnu, Farber-Eger, Eric H, Finan, Chris, Garnier, Sophie, Ghouse, Jonas, Giedraitis, Vilmantas, Guðbjartsson, Daniel F, Haggerty, Christopher M, Halliday, Brian P, Helgadottir, Anna, Hemingway, Harry, Hillege, Hans L, Kardys, Isabella, Lind, Lars, Lindgren, Cecilia M, Lowery, Brandon D, Manisty, Charlotte, Margulies, Kenneth B, Moon, James C, Mordi, Ify R, Morley, Michael P, Morris, Andrew D, Morris, Andrew P, Morton, Lori, Noursadeghi, Mahdad, Ostrowski, Sisse R, Owens, Anjali T, Palmer, Colin N A, Pantazis, Antonis, Pedersen, Ole B V, Prasad, Sanjay K, Shekhar, Akshay, Smelser, Diane T, Srinivasan, Sundararajan, Stefansson, Kari, Sveinbjörnsson, Garðar, Syrris, Petros, Tammesoo, Mari-Liis, Tayal, Upasana, Teder-Laving, Maris, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Tragante, Vinicius, Trégouët, David-Alexandre, Treibel, Thomas A, Ullum, Henrik, Valdes, Ana M, van Setten, Jessica, van Vugt, Marion, Veluchamy, Abirami, Verschuren, W M Monique, Villard, Eric, Yang, Yifan, Asselbergs, Folkert W, Cappola, Thomas P, Dube, Marie-Pierre, Dunn, Michael E, Ellinor, Patrick T, Hingorani, Aroon D, Lang, Chim C, Samani, Nilesh J, Shah, Svati H, Smith, J Gustav, Vasan, Ramachandran S, O'Regan, Declan P, Holm, Hilma, Noseda, Michela, Wells, Quinn, Ware, James S, and Lumbers, R Thomas
- Abstract
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L and SSPN). Using single-nucleus transcriptomics, we identify cellular states, biological pathways, and intracellular communications that drive pathogenesis. We demonstrate that polygenic scores predict DCM in the general population and modify penetrance in carriers of rare DCM variants. Our findings may inform the design of genetic testing strategies that incorporate polygenic background. They also provide insights into the molecular etiology of DCM that may facilitate the development of targeted therapeutics.
- Published
- 2024
- Full Text
- View/download PDF
45. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels
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Gezonde Vaten, Circulatory Health, de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjamin A.T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Suchon, Pierre, Guo, Xiuqing, Rosendaal, Frits R., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., van der Harst, Pim, Trans-Omics for Precision Medicine (TOPMed) program, the INVENT consortium, Gezonde Vaten, Circulatory Health, de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjamin A.T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Suchon, Pierre, Guo, Xiuqing, Rosendaal, Frits R., Klaric, Lucija, Noordam, Raymond, van Rooij, Frank, Curran, Joanne E., Wheeler, Marsha M., van der Harst, Pim, Trans-Omics for Precision Medicine (TOPMed) program, and the INVENT consortium
- Published
- 2024
46. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels
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de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjamin A.T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Hansen, Torben, Chen, Wei Min, Jackson, Rebecca, Liu, Yu, Loos, Ruth J.F., Rao, D. C., Wang, Lu, Nielsen, Jonas B., Kilpeläinen, Tuomas O., de Vries, Paul S., Reventun, Paula, Brown, Michael R., Heath, Adam S., Huffman, Jennifer E., Le, Ngoc Quynh, Bebo, Allison, Brody, Jennifer A., Temprano-Sagrera, Gerard, Raffield, Laura M., Ozel, Ayse Bilge, Thibord, Florian, Jain, Deepti, Lewis, Joshua P., Rodriguez, Benjamin A.T., Pankratz, Nathan, Taylor, Kent D., Polasek, Ozren, Chen, Ming Huei, Yanek, Lisa R., Carrasquilla, German D., Marioni, Riccardo E., Kleber, Marcus E., Trégouët, David Alexandre, Yao, Jie, Li-Gao, Ruifang, Joshi, Peter K., Trompet, Stella, Martinez-Perez, Angel, Ghanbari, Mohsen, Howard, Tom E., Reiner, Alex P., Arvanitis, Marios, Ryan, Kathleen A., Bartz, Traci M., Rudan, Igor, Faraday, Nauder, Linneberg, Allan, Ekunwe, Lynette, Davies, Gail, Delgado, Graciela E., Hansen, Torben, Chen, Wei Min, Jackson, Rebecca, Liu, Yu, Loos, Ruth J.F., Rao, D. C., Wang, Lu, Nielsen, Jonas B., and Kilpeläinen, Tuomas O.
- Abstract
Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10−9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro., Coagulation factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are critical to coagulation and platelet aggregation. We leveraged whole-genome sequence data from the Trans-Omics for Precision Medicine (TOPMed) program along with TOPMed-based imputation of genotypes in additional samples to identify genetic associations with circulating FVIII and VWF levels in a single-variant meta-analysis, including up to 45 289 participants. Gene-based aggregate tests were implemented in TOPMed. We identified 3 candidate causal genes and tested their functional effect on FVIII release from human liver endothelial cells (HLECs) and VWF release from human umbilical vein endothelial cells. Mendelian randomization was also performed to provide evidence for causal associations of FVIII and VWF with thrombotic outcomes. We identified associations (P < 5 × 10−9) at 7 new loci for FVIII (ST3GAL4, CLEC4M, B3GNT2, ASGR1, F12, KNG1, and TREM1/NCR2) and 1 for VWF (B3GNT2). VWF, ABO, and STAB2 were associated with FVIII and VWF in gene-based analyses. Multiphenotype analysis of FVIII and VWF identified another 3 new loci, including PDIA3. Silencing of B3GNT2 and the previously reported CD36 gene decreased release of FVIII by HLECs, whereas silencing of B3GNT2, CD36, and PDIA3 decreased release of VWF by HVECs. Mendelian randomization supports causal association of higher FVIII and VWF with increased risk of thrombotic outcomes. Seven new loci were identified for FVIII and 1 for VWF, with evidence supporting causal associations of FVIII and VWF with thrombotic outcomes. B3GNT2, CD36, and PDIA3 modulate the release of FVIII and/or VWF in vitro.
- Published
- 2024
47. Prediction of Causal Candidate Genes in Coronary Artery Disease Loci
- Author
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Brænne, Ingrid, Civelek, Mete, Vilne, Baiba, Di Narzo, Antonio, Johnson, Andrew D, Zhao, Yuqi, Reiz, Benedikt, Codoni, Veronica, Webb, Thomas R, Foroughi Asl, Hassan, Hamby, Stephen E, Zeng, Lingyao, Trégouët, David-Alexandre, Hao, Ke, Topol, Eric J, Schadt, Eric E, Yang, Xia, Samani, Nilesh J, Björkegren, Johan LM, Erdmann, Jeanette, Schunkert, Heribert, and Lusis, Aldons J
- Subjects
Heart Disease ,Cardiovascular ,Atherosclerosis ,Biotechnology ,Heart Disease - Coronary Heart Disease ,Human Genome ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Coronary Artery Disease ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genetic Variation ,Genome-Wide Association Study ,Humans ,Male ,MicroRNAs ,Polymorphism ,Single Nucleotide ,Predictive Value of Tests ,Promoter Regions ,Genetic ,coronary artery disease ,genome-wide association study ,microRNAs ,single-nucleotide polymorphism ,systems biology ,Leducq Consortium CAD Genomics‡ ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Cardiovascular System & Hematology - Abstract
ObjectiveGenome-wide association studies have to date identified 159 significant and suggestive loci for coronary artery disease (CAD). We now report comprehensive bioinformatics analyses of sequence variation in these loci to predict candidate causal genes.Approach and resultsAll annotated genes in the loci were evaluated with respect to protein-coding single-nucleotide polymorphism and gene expression parameters. The latter included expression quantitative trait loci, tissue specificity, and miRNA binding. High priority candidate genes were further identified based on literature searches and our experimental data. We conclude that the great majority of causal variations affecting CAD risk occur in noncoding regions, with 41% affecting gene expression robustly versus 6% leading to amino acid changes. Many of these genes differed from the traditionally annotated genes, which was usually based on proximity to the lead single-nucleotide polymorphism. Indeed, we obtained evidence that genetic variants at CAD loci affect 98 genes which had not been linked to CAD previously.ConclusionsOur results substantially revise the list of likely candidates for CAD and suggest that genome-wide association studies efforts in other diseases may benefit from similar bioinformatics analyses.
- Published
- 2015
48. Maximizing the Power of Principal Components Analysis of Correlated Phenotypes in Genome-wide Association Studies
- Author
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Aschard, Hugues, Vilhjálmsson, Bjarni J., Greliche, Nicolas, Morange, Pierre-Emmanuel, Trégouët, David-Alexandre, and Kraft, Peter
- Subjects
Statistics - Methodology - Abstract
Principal Component analysis (PCA) is a useful statistical technique that is commonly used for multivariate analysis of correlated variables. It is usually applied as a dimension reduction method: the top principal components (PCs) explaining most of total variance are tested for association with a predictor of interest, and the remaining PCs are ignored. This strategy has been widely applied in genetic epidemiology, however some of its aspects are not well appreciated in the context of single nucleotide polymorphisms (SNPs) association testing. In this study, we review the theoretical basis of PCA and its behavior when testing for association between a SNP and two correlated traits under various scenarios. We then evaluate with simulations the power of several different PCA-based strategies when analyzing up to 100 correlated traits. We show that contrary to widespread practice that testing the top PCs only can be dramatically underpowered since PCs explaining a low amount of the total phenotypic variance can harbor substantial genetic associations. Furthermore, we demonstrate that PC-based strategies that use all PCs have great potential to detect negatively pleiotropic genetic variants (e.g. variants with opposite effects on positively correlated traits) and genetic variants that are exclusively associated with a single trait, but only achieve a moderate gain in power to detect positive pleiotropic genetic loci. Finally, the genome-wide association study of five correlated coagulation traits in 685 subjects from the MARTHA study confirms these results. The joint analysis of the five PCs from the coagulation traits identified two new candidate SNPs, which were most strongly associated with the 5th PC that explained the smallest amount of phenotypic variance.
- Published
- 2013
49. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism
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Lindström, Sara, Wang, Lu, Smith, Erin N., Gordon, William, van Hylckama Vlieg, Astrid, de Andrade, Mariza, Brody, Jennifer A., Pattee, Jack W., Haessler, Jeffrey, Brumpton, Ben M., Chasman, Daniel I., Suchon, Pierre, Chen, Ming-Huei, Turman, Constance, Germain, Marine, Wiggins, Kerri L., MacDonald, James, Braekkan, Sigrid K., Armasu, Sebastian M., Pankratz, Nathan, Jackson, Rebecca D., Nielsen, Jonas B., Giulianini, Franco, Puurunen, Marja K., Ibrahim, Manal, Heckbert, Susan R., Damrauer, Scott M., Natarajan, Pradeep, Klarin, Derek, de Vries, Paul S., Sabater-Lleal, Maria, Huffman, Jennifer E., Bammler, Theo K., Frazer, Kelly A., McCauley, Bryan M., Taylor, Kent, Pankow, James S., Reiner, Alexander P., Gabrielsen, Maiken E., Deleuze, Jean-François, O'Donnell, Chris J., Kim, Jihye, McKnight, Barbara, Kraft, Peter, Hansen, John-Bjarne, Rosendaal, Frits R., Heit, John A., Psaty, Bruce M., Tang, Weihong, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M., Morange, Pierre-Emmanuel, Johnson, Andrew D., Kabrhel, Christopher, Trégouët, David-Alexandre, and Smith, Nicholas L.
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- 2019
- Full Text
- View/download PDF
50. A Genome Wide Association Study on plasma FV levels identified PLXDC2 as a new modifier of the coagulation process
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Thibord, Florian, Hardy, Lise, Ibrahim‐Kosta, Manal, Saut, Noémie, Pulcrano‐Nicolas, Anne‐Sophie, Goumidi, Louisa, Civelek, Mete, Eriksson, Per, Deleuze, Jean‐François, Le Goff, Wilfried, Trégouët, David‐Alexandre, and Morange, Pierre‐Emmanuel
- Published
- 2019
- Full Text
- View/download PDF
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