Search

Your search keyword '"Vinuela, Ana"' showing total 37 results
Start Over Author "Vinuela, Ana" Search Limiters Available in Library Collection
37 results on '"Vinuela, Ana"'

1. Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Author

Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren

Published
2023
Full Text
View/download PDF

4. Author Correction: Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Author

Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren

Published
2023
Full Text
View/download PDF

5. Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

Author

Anand, Shankara, Gabriel, Stacey, Getz, Gad A., Graubert, Aaron, Hadley, Kane, Handsaker, Robert E., Huang, Katherine H., Li, Xiao, MacArthur, Daniel G., Meier, Samuel R., Nedzel, Jared L., Nguyen, Duyen T., Segrè, Ayellet V., Todres, Ellen, Balliu, Brunilda, Bonazzola, Rodrigo, Brown, Andrew, Conrad, Donald F., Cotter, Daniel J., Cox, Nancy, Das, Sayantan, Dermitzakis, Emmanouil T., Einson, Jonah, Engelhardt, Barbara E., Eskin, Eleazar, Flynn, Elise D., Fresard, Laure, Gamazon, Eric R., Garrido-Martín, Diego, Gay, Nicole R., Guigó, Roderic, Hamel, Andrew R., He, Yuan, Hoffman, Paul J., Hormozdiari, Farhad, Hou, Lei, Jo, Brian, Kasela, Silva, Kashin, Seva, Kellis, Manolis, Kwong, Alan, Li, Xin, Liang, Yanyu, Mangul, Serghei, Mohammadi, Pejman, Muñoz-Aguirre, Manuel, Nobel, Andrew B., Oliva, Meritxell, Park, Yongjin, Parsana, Princy, Reverter, Ferran, Rouhana, John M., Sabatti, Chiara, Saha, Ashis, Stephens, Matthew, Stranger, Barbara E., Teran, Nicole A., Viñuela, Ana, Wang, Gao, Wright, Fred, Wucher, Valentin, Zou, Yuxin, Ferreira, Pedro G., Li, Gen, Melé, Marta, Yeger-Lotem, Esti, Bradbury, Debra, Krubit, Tanya, McLean, Jeffrey A., Qi, Liqun, Robinson, Karna, Roche, Nancy V., Smith, Anna M., Tabor, David E., Undale, Anita, Bridge, Jason, Brigham, Lori E., Foster, Barbara A., Gillard, Bryan M., Hasz, Richard, Hunter, Marcus, Johns, Christopher, Johnson, Mark, Karasik, Ellen, Kopen, Gene, Leinweber, William F., McDonald, Alisa, Moser, Michael T., Myer, Kevin, Ramsey, Kimberley D., Roe, Brian, Shad, Saboor, Thomas, Jeffrey A., Walters, Gary, Washington, Michael, Wheeler, Joseph, Jewell, Scott D., Rohrer, Daniel C., Valley, Dana R., Davis, David A., Mash, Deborah C., Barcus, Mary E., Branton, Philip A., Sobin, Leslie, Barker, Laura K., Gardiner, Heather M., Mosavel, Maghboeba, Siminoff, Laura A., Flicek, Paul, Haeussler, Maximilian, Juettemann, Thomas, Kent, W. James, Lee, Christopher M., Powell, Conner C., Rosenbloom, Kate R., Ruffier, Magali, Sheppard, Dan, Taylor, Kieron, Trevanion, Stephen J., Zerbino, Daniel R., Abell, Nathan S., Akey, Joshua, Chen, Lin, Demanelis, Kathryn, Doherty, Jennifer A., Feinberg, Andrew P., Hansen, Kasper D., Hickey, Peter F., Jasmine, Farzana, Jiang, Lihua, Kaul, Rajinder, Kibriya, Muhammad G., Li, Jin Billy, Li, Qin, Lin, Shin, Linder, Sandra E., Pierce, Brandon L., Rizzardi, Lindsay F., Skol, Andrew D., Smith, Kevin S., Snyder, Michael, Stamatoyannopoulos, John, Tang, Hua, Wang, Meng, Carithers, Latarsha J., Guan, Ping, Koester, Susan E., Little, A. Roger, Moore, Helen M., Nierras, Concepcion R., Rao, Abhi K., Vaught, Jimmie B., Volpi, Simona, de Goede, Olivia M., Nachun, Daniel C., Ferraro, Nicole M., Gloudemans, Michael J., Rao, Abhiram S., Smail, Craig, Eulalio, Tiffany Y., Aguet, François, Ng, Bernard, Xu, Jishu, Barbeira, Alvaro N., Castel, Stephane E., Kim-Hellmuth, Sarah, Park, YoSon, Scott, Alexandra J., Strober, Benjamin J., Brown, Christopher D., Wen, Xiaoquan, Hall, Ira M., Battle, Alexis, Lappalainen, Tuuli, Im, Hae Kyung, Ardlie, Kristin G., Mostafavi, Sara, Quertermous, Thomas, Kirkegaard, Karla, and Montgomery, Stephen B.

Published
2021
Full Text
View/download PDF

7. Dissecting the interplay between ageing, sex and body mass index on a molecular level

Author

Michalettou, Theodora Dafni, Hong, Mun-Gwan, Fernandez, Juan, Sharma, Sapna, Brorsson, Caroline, Koivula, Robert, Adamski, Jerzy, Brunak, Soren, Dermitzakis, Emmanouil, Franks, Paul, McCarthy, Mark, Pearson, Ewan, Schwenk, Jochen M., Walker, Mark, Brown, Andrew, Vinuela, Ana, Michalettou, Theodora Dafni, Hong, Mun-Gwan, Fernandez, Juan, Sharma, Sapna, Brorsson, Caroline, Koivula, Robert, Adamski, Jerzy, Brunak, Soren, Dermitzakis, Emmanouil, Franks, Paul, McCarthy, Mark, Pearson, Ewan, Schwenk, Jochen M., Walker, Mark, Brown, Andrew, and Vinuela, Ana

Abstract

QC 20240301

Published
2024

8. A Quantitative Proteome Map of the Human Body

Author

Aguet, François, Anand, Shankara, Ardlie, Kristin G., Gabriel, Stacey, Getz, Gad, Graubert, Aaron, Hadley, Kane, Handsaker, Robert E., Huang, Katherine H., Kashin, Seva, MacArthur, Daniel G., Meier, Samuel R., Nedzel, Jared L., Nguyen, Duyen Y., Segrè, Ayellet V., Todres, Ellen, Balliu, Brunilda, Barbeira, Alvaro N., Battle, Alexis, Bonazzola, Rodrigo, Brown, Andrew, Brown, Christopher D., Castel, Stephane E., Conrad, Don, Cotter, Daniel J., Cox, Nancy, Das, Sayantan, de Goede, Olivia M., Dermitzakis, Emmanouil T., Engelhardt, Barbara E., Eskin, Eleazar, Eulalio, Tiffany Y., Ferraro, Nicole M., Flynn, Elise, Fresard, Laure, Gamazon, Eric R., Garrido-Martín, Diego, Gay, Nicole R., Guigó, Roderic, Hamel, Andrew R., He, Yuan, Hoffman, Paul J., Hormozdiari, Farhad, Hou, Lei, Im, Hae Kyung, Jo, Brian, Kasela, Silva, Kellis, Manolis, Kim-Hellmuth, Sarah, Kwong, Alan, Lappalainen, Tuuli, Li, Xin, Liang, Yanyu, Mangul, Serghei, Mohammadi, Pejman, Montgomery, Stephen B., Muñoz-Aguirre, Manuel, Nachun, Daniel C., Nobel, Andrew B., Oliva, Meritxell, Park, YoSon, Park, Yongjin, Parsana, Princy, Reverter, Ferran, Rouhana, John M., Sabatti, Chiara, Saha, Ashis, Skol, Andrew D., Stephens, Matthew, Stranger, Barbara E., Strober, Benjamin J., Teran, Nicole A., Viñuela, Ana, Wang, Gao, Wen, Xiaoquan, Wright, Fred, Wucher, Valentin, Zou, Yuxin, Ferreira, Pedro G., Li, Gen, Melé, Marta, Yeger-Lotem, Esti, Barcus, Mary E., Bradbury, Debra, Krubit, Tanya, McLean, Jeffrey A., Qi, Liqun, Robinson, Karna, Roche, Nancy V., Smith, Anna M., Sobin, Leslie, Tabor, David E., Undale, Anita, Bridge, Jason, Brigham, Lori E., Foster, Barbara A., Gillard, Bryan M., Hasz, Richard, Hunter, Marcus, Johns, Christopher, Johnson, Mark, Karasik, Ellen, Kopen, Gene, Leinweber, William F., McDonald, Alisa, Moser, Michael T., Myer, Kevin, Ramsey, Kimberley D., Roe, Brian, Shad, Saboor, Thomas, Jeffrey A., Walters, Gary, Washington, Michael, Wheeler, Joseph, Jewell, Scott D., Rohrer, Daniel C., Valley, Dana R., Davis, David A., Mash, Deborah C., Branton, Philip A., Barker, Laura K., Gardiner, Heather M., Mosavel, Maghboeba, Siminoff, Laura A., Flicek, Paul, Haeussler, Maximilian, Juettemann, Thomas, Kent, W. James, Lee, Christopher M., Powell, Conner C., Rosenbloom, Kate R., Ruffier, Magali, Sheppard, Dan, Taylor, Kieron, Trevanion, Stephen J., Zerbino, Daniel R., Abell, Nathan S., Akey, Joshua, Chen, Lin, Demanelis, Kathryn, Doherty, Jennifer A., Feinberg, Andrew P., Hansen, Kasper D., Hickey, Peter F., Jasmine, Farzana, Kaul, Rajinder, Kibriya, Muhammad G., Li, Jin Billy, Li, Qin, Linder, Sandra E., Pierce, Brandon L., Rizzardi, Lindsay F., Smith, Kevin S., Stamatoyannopoulos, John, Tang, Hua, Carithers, Latarsha J., Guan, Ping, Koester, Susan E., Little, A. Roger, Moore, Helen M., Nierras, Concepcion R., Rao, Abhi K., Vaught, Jimmie B., Volpi, Simona, Jiang, Lihua, Wang, Meng, Lin, Shin, Jian, Ruiqi, Li, Xiao, Chan, Joanne, Dong, Guanlan, Fang, Huaying, Robinson, Aaron E., and Snyder, Michael P.

Published
2020
Full Text
View/download PDF

9. Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: An IMI DIRECT study

Author

Eriksen, Rebeca, Perez, Isabel Garcia, Posma, Joram M., Haid, Mark, Sharma, Sapna, Prehn, Cornelia, Thomas, Louise E., Koivula, Robert W., Bizzotto, Roberto, Mari, Andrea, Giordano, Giuseppe N., Pavo, Imre, Schwenk, Jochen M., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Viñuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Rutter, Femke, Teare, Harriet, Hansen, Tue H., Fernandez, Juan, Jones, Angus, Jennison, Chris, Walker, Mark, McCarthy, Mark I., Pedersen, Oluf, Ruetten, Hartmut, Forgie, Ian, Bell, Jimmy D., Pearson, Ewan R., Franks, Paul W., Adamski, Jerzy, Holmes, Elaine, and Frost, Gary

Published
2020
Full Text
View/download PDF

10. Genome-Wide Association Shows that Pigmentation Genes Play a Role in Skin Aging

Author

Law, Matthew H., Medland, Sarah E., Zhu, Gu, Yazar, Seyhan, Viñuela, Ana, Wallace, Leanne, Shekar, Sri Niranjan, Duffy, David L., Bataille, Veronique, Glass, Dan, Spector, Tim D., Wood, Diane, Gordon, Scott D., Barbour, Julie M., Henders, Anjali K., Hewitt, Alex W., Montgomery, Grant W., Sturm, Richard A., Mackey, David A., Green, Adèle C., Martin, Nicholas G., and MacGregor, Stuart

Published
2017
Full Text
View/download PDF

11. Identification of shared molecular signatures of ageing and metabolic diseases using multi-omic data

Author

Michalettou, Theodora Dafni, Hong, Mun-Gwan, Fernandez, Juan, Sharma, Sapna, Brorsson, Caroline Anna, Koivula, Robert, Adamski, Jerzy, Brunak, Soren, Dermitzakis, Emmanouil, Franks, Paul, McCarthy, Mark, Pearson, Ewan, Schwenk, Jochen, Walker, Mark, Brown, Andrew, Vinuela, Ana, Michalettou, Theodora Dafni, Hong, Mun-Gwan, Fernandez, Juan, Sharma, Sapna, Brorsson, Caroline Anna, Koivula, Robert, Adamski, Jerzy, Brunak, Soren, Dermitzakis, Emmanouil, Franks, Paul, McCarthy, Mark, Pearson, Ewan, Schwenk, Jochen, Walker, Mark, Brown, Andrew, and Vinuela, Ana

Abstract

QC 20231128

Published
2023

12. Discovery of Type 2 Diabetes genes using an accessible tissue

Author

Davtian, David, Schwenk, Jochen M., McCarthy, Mark, Mahajan, Anubha, Hong, Mun-Gwan, Dermitzakis, Emmanouil, Im, Hae Kyung, Pearson, Ewan, Vinuela, Ana, Brown, Andrew, Davtian, David, Schwenk, Jochen M., McCarthy, Mark, Mahajan, Anubha, Hong, Mun-Gwan, Dermitzakis, Emmanouil, Im, Hae Kyung, Pearson, Ewan, Vinuela, Ana, and Brown, Andrew

Abstract

QC 20231121

Published
2023

13. Proteomic analysis of 92 circulating proteins and their effects in cardiometabolic diseases

Author

Carland, Corinne, Png, Grace, Malarstig, Anders, Kho, Pik Fang, Gustafsson, Stefan, Michaëlsson, Karl, Lind, Lars, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, Ramisch, Anna, Macdonald-Dunlop, Erin, Klaric, Lucija K., Joshi, Peter, Chen, Yan M., Bjoerck, Hanna, Eriksson, Per, Carrasco-Zanini, Julia, Wheeler, Eleanor, Suhre, Karsten, Gilly, Arthur, Zeggini, Eleftheria, Vinuela, Ana T., Dermitzakis, Emmanouil F., Wilson, James, Langenberg, Claudia, Thareja, Gaurav, Halama, Anna, Schmidt, Frank, Zanetti, Daniela, Assimes, Themistocles, Consortium, S C A L L O P, Carland, Corinne, Png, Grace, Malarstig, Anders, Kho, Pik Fang, Gustafsson, Stefan, Michaëlsson, Karl, Lind, Lars, Tsafantakis, Emmanouil, Karaleftheri, Maria, Dedoussis, George, Ramisch, Anna, Macdonald-Dunlop, Erin, Klaric, Lucija K., Joshi, Peter, Chen, Yan M., Bjoerck, Hanna, Eriksson, Per, Carrasco-Zanini, Julia, Wheeler, Eleanor, Suhre, Karsten, Gilly, Arthur, Zeggini, Eleftheria, Vinuela, Ana T., Dermitzakis, Emmanouil F., Wilson, James, Langenberg, Claudia, Thareja, Gaurav, Halama, Anna, Schmidt, Frank, Zanetti, Daniela, Assimes, Themistocles, and Consortium, S C A L L O P

Abstract

Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.

Published
2023
Full Text
View/download PDF

14. Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models:[with Author Correction]

Author

Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B, De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T, 't Hart, Leen M, Pattou, Francois, Raverdy, Violeta, Brage, Soren, Ridderstråle, Martin, Pedersen, Oluf, Hansen, Torben, Banasik, Karina, Rasmussen, Simon, Brunak, Søren, Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B, De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T, 't Hart, Leen M, Pattou, Francois, Raverdy, Violeta, Brage, Soren, Ridderstråle, Martin, Pedersen, Oluf, Hansen, Torben, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren

Abstract

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.

Published
2023

16. Genetic Landscape of the ACE2 Coronavirus Receptor

Author

Yang, Zhijian, Macdonald-Dunlop, Erin, Chen, Jiantao, Zhai, Ranran, Li, Ting, Richmond, Anne, Klaric, Lucija, Pirastu, Nicola, Ning, Zheng, Zheng, Chenqing, Wang, Yipeng, Huang, Tingting, He, Yazhou, Guo, Huiming, Ying, Kejun, Gustafsson, Stefan, Prins, Bram, Ramisch, Anna, Dermitzakis, Emmanouil T., Png, Grace, Eriksson, Niclas, Haessler, Jeffrey, Hu, Xiaowei, Zanetti, Daniela, Boutin, Thibaud, Hwang, Shih-Jen, Wheeler, Eleanor, Pietzner, Maik, Raffield, Laura M., Kalnapenkis, Anette, Peters, James E., Vinuela, Ana, Gilly, Arthur, Elmstahl, Solve, Dedoussis, George, Petrie, John R., Polasek, Ozren, Folkersen, Lasse, Chen, Yan, Yao, Chen, Vosa, Urmo, Pairo-Castineira, Erola, Clohisey, Sara, Bretherick, Andrew D., Rawlik, Konrad, Esko, Tonu, Enroth, Stefan, Johansson, Åsa, Gyllensten, Ulf B., Langenberg, Claudia, Levy, Daniel, Hayward, Caroline, Assimes, Themistocles L., Kooperberg, Charles, Manichaikul, Ani W., Siegbahn, Agneta, Wallentin, Lars, Lind, Lars, Zeggini, Eleftheria, Schwenk, Jochen M., Butterworth, Adam S., Michaëlsson, Karl, Pawitan, Yudi, Joshi, Peter K., Baillie, J. Kenneth, Malarstig, Anders, Reiner, Alexander P., Wilson, James F., Shen, Xia, Yang, Zhijian, Macdonald-Dunlop, Erin, Chen, Jiantao, Zhai, Ranran, Li, Ting, Richmond, Anne, Klaric, Lucija, Pirastu, Nicola, Ning, Zheng, Zheng, Chenqing, Wang, Yipeng, Huang, Tingting, He, Yazhou, Guo, Huiming, Ying, Kejun, Gustafsson, Stefan, Prins, Bram, Ramisch, Anna, Dermitzakis, Emmanouil T., Png, Grace, Eriksson, Niclas, Haessler, Jeffrey, Hu, Xiaowei, Zanetti, Daniela, Boutin, Thibaud, Hwang, Shih-Jen, Wheeler, Eleanor, Pietzner, Maik, Raffield, Laura M., Kalnapenkis, Anette, Peters, James E., Vinuela, Ana, Gilly, Arthur, Elmstahl, Solve, Dedoussis, George, Petrie, John R., Polasek, Ozren, Folkersen, Lasse, Chen, Yan, Yao, Chen, Vosa, Urmo, Pairo-Castineira, Erola, Clohisey, Sara, Bretherick, Andrew D., Rawlik, Konrad, Esko, Tonu, Enroth, Stefan, Johansson, Åsa, Gyllensten, Ulf B., Langenberg, Claudia, Levy, Daniel, Hayward, Caroline, Assimes, Themistocles L., Kooperberg, Charles, Manichaikul, Ani W., Siegbahn, Agneta, Wallentin, Lars, Lind, Lars, Zeggini, Eleftheria, Schwenk, Jochen M., Butterworth, Adam S., Michaëlsson, Karl, Pawitan, Yudi, Joshi, Peter K., Baillie, J. Kenneth, Malarstig, Anders, Reiner, Alexander P., Wilson, James F., and Shen, Xia

Abstract

Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells. Conclusions: Human plasma ACE2 shares a genetic basis with cardi

Published
2022
Full Text
View/download PDF

17. Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: An IMI DIRECT study

Author

Wesolowska-Andersen, Agata, primary, Brorsson, Caroline A., additional, Bizzotto, Roberto, additional, Mari, Andrea, additional, Tura, Andrea, additional, Koivula, Robert, additional, Mahajan, Anubha, additional, Vinuela, Ana, additional, Tajes, Juan Fernandez, additional, Sharma, Sapna, additional, Haid, Mark, additional, Prehn, Cornelia, additional, Artati, Anna, additional, Hong, Mun-Gwan, additional, Musholt, Petra B., additional, Kurbasic, Azra, additional, De Masi, Federico, additional, Tsirigos, Kostas, additional, Pedersen, Helle Krogh, additional, Gudmundsdottir, Valborg, additional, Thomas, Cecilia Engel, additional, Banasik, Karina, additional, Jennison, Chrisopher, additional, Jones, Angus, additional, Kennedy, Gwen, additional, Bell, Jimmy, additional, Thomas, Louise, additional, Frost, Gary, additional, Thomsen, Henrik, additional, Allin, Kristine, additional, Hansen, Tue Haldor, additional, Vestergaard, Henrik, additional, Hansen, Torben, additional, Rutters, Femke, additional, Elders, Petra, additional, t’Hart, Leen, additional, Bonnefond, Amelie, additional, Canouil, Mickaël, additional, Brage, Soren, additional, Kokkola, Tarja, additional, Heggie, Alison, additional, McEvoy, Donna, additional, Hattersley, Andrew, additional, McDonald, Timothy, additional, Teare, Harriet, additional, Ridderstrale, Martin, additional, Walker, Mark, additional, Forgie, Ian, additional, Giordano, Giuseppe N., additional, Froguel, Philippe, additional, Pavo, Imre, additional, Ruetten, Hartmut, additional, Pedersen, Oluf, additional, Dermitzakis, Emmanouil, additional, Franks, Paul W., additional, Schwenk, Jochen M., additional, Adamski, Jerzy, additional, Pearson, Ewan, additional, McCarthy, Mark I., additional, and Brunak, Søren, additional

Published
2022
Full Text
View/download PDF

18. Correction to: The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study (Diabetologia, (2020), 63, 4, (744-756), 10.1007/s00125-019-05083-6)

Author

Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, S. ren, Brunak, S. ren, de Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J. A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W., Epidemiology and Data Science, ACS - Diabetes & metabolism, APH - Health Behaviors & Chronic Diseases, APH - Aging & Later Life, and ACS - Heart failure & arrhythmias

Abstract

Unfortunately, ‘Present address’ was omitted from one of the addresses provided for Mark I. McCarthy (#26). The corrected address details are given on the following page.

Published
2021
Full Text
View/download PDF

19. Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity

Author

Deshmukh, Harshal A., Madsen, Anne Lundager, Vinuela, Ana, Have, Christian Theil, Grarup, Niels, Tura, Andrea, Mahajan, Anubha, Heggie, Alison J., Koivula, Robert W., De Masi, Federico, Tsirigos, Konstantinos K., Linneberg, Allan, Drivsholm, Thomas, Pedersen, Oluf, Sorensen, Thorkild I. A., Astrup, Arne, Gjesing, Anette A. P., Pavo, Imre, Wood, Andrew R., Ruetten, Hartmut, Jones, Angus G., Koopman, Anitra D. M., Cederberg, Henna, Rutters, Femke, Ridderstrale, Martin, Laakso, Markku, McCarthy, Mark, I, Frayling, Tim M., Ferrannini, Ele, Franks, Paul W., Pearson, Ewan R., Mari, Andrea, Hansen, Torben, Walker, Mark, Deshmukh, Harshal A., Madsen, Anne Lundager, Vinuela, Ana, Have, Christian Theil, Grarup, Niels, Tura, Andrea, Mahajan, Anubha, Heggie, Alison J., Koivula, Robert W., De Masi, Federico, Tsirigos, Konstantinos K., Linneberg, Allan, Drivsholm, Thomas, Pedersen, Oluf, Sorensen, Thorkild I. A., Astrup, Arne, Gjesing, Anette A. P., Pavo, Imre, Wood, Andrew R., Ruetten, Hartmut, Jones, Angus G., Koopman, Anitra D. M., Cederberg, Henna, Rutters, Femke, Ridderstrale, Martin, Laakso, Markku, McCarthy, Mark, I, Frayling, Tim M., Ferrannini, Ele, Franks, Paul W., Pearson, Ewan R., Mari, Andrea, Hansen, Torben, and Walker, Mark

Abstract

Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity. Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies. Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models. Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10−9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10−9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity. Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

Published
2021
Full Text
View/download PDF

20. Processes Underlying Glycemic Deterioration in Type 2 Diabetes:An IMI DIRECT Study

Author

Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., Mari, Andrea, Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., and Mari, Andrea

Abstract

OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent

Published
2021

21. Les lucarnes de l’Europe

Author

Aldridge, Mark, Alvès, Patrick, Autissier, Anne-Marie, Brunner, Joséphine, Chaniac, Régine, Defrance, Corine, Denéchère, Yves, Frank, Robert, Freissinier, Gilles, García Nicolás, Cristina, Hallenberger, Gerd, Humblot, Catherine, Lefort, Pierre, Lévy, Marie-Françoise, Lits, Marc, Mazdon, Lucy, Merolla, Marilisa, Sellier, Yannick, Sicard, Marie-Noële, Torterat, Lucile, Utard, Jean-Michel, Vallotton, François, Vinuela, Ana, Lévy, Marie-Françoise, and Sicard, Marie-Noële

Subjects
construction européenne, History, télévision, Anthropology, HB, patrimoine, HIS000000, téléspectateur, mode de vie, identité, média, culture, espace audiovisuel
Abstract

LA TÉLÉVISION EST AU CENTRE DE CE LIVRE. Et l’Europe aussi. Croiser l’histoire des « étranges lucarnes» - comme un journal satirique français se plaisait à appeler ce nouveau média - avec l’histoire de la construction européenne, tel est l’objectif de cet ouvrage collectif. Le livre propose de penser cette double histoire è la lumière d’un double questionnement: Y a-t-il eu construction d’un espace audiovisuel européen? Et. si oui, ce dernier a-t-il contribué à construire une Europe culturelle et à forger une identité européenne nouvelle? Comme le montrent Marie-Françoise Lévy et Maric-Noëlle Sicard dans leur introduction, les questions posées ne donnent pas lieu à des réponses univoques. D’autant que les auteurs de ce volume engagent des réflexions sur la notion même do culture et sur celle d’identité. Toutes les contributions ici rassemblées apportent des éclairages nouveaux sur ces concepts, sur la façon dont ils sont appréhendés, ainsi que sur la dimension culturelle et identitaire de la télévision en Europe depuis un demi-siècle. Ce livre analyse les modèles de télévision et leurs transformations, la relance de l’Europe de la culture, les difficultés et les obstacles rencontrés par les acteurs qui tentent de conjuguer télévision, culture et Europe. Il étudie également les programmes télévisuels, ces récits et ces images qui montrent l’Europe, en dessinent les signes de reconnaissance et offrent au téléspectateur un élargissement de son horizon national vers d’autres paysages, modes de vie, patrimoines et traditions culturelles. A travers cette démarche novatrice, les télévisions apparaissent ainsi comme des acteurs de l’histoire de l’Europe.

Published
2020

22. La politique audiovisuelle de l’Union européenne

Author

Vinuela, Ana

Subjects
construction européenne, History, télévision, Anthropology, HB, patrimoine, HIS000000, téléspectateur, mode de vie, identité, média, culture, espace audiovisuel
Abstract

Les mesures adoptées par l’Union européenne pour soutenir l’industrie audiovisuelle visent à apporter des réponses à caractère normatif, incitatif et structurant à un ensemble de collectifs professionnels, de groupes d’intérêt et d’acteurs de différentes tailles et natures : sociétés de production cinématographique, audiovisuelle et multimédia ; chaînes de télévision et opérateurs de télécommunications. Avec des moyens insuffisants pour atteindre les objectifs industriels, culturels et politi...

Published
2020

23. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes:an IMI DIRECT study

Author

Koivula, Robert W, Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N, White, Tom, Adamski, Jerzy, Bell, Jimmy D, Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T, Forgie, Ian M, Frost, Gary, Hansen, Torben, Hansen, Tue H, Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J, Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M, Teare, Harriet J A, Thomas, E Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W, Koivula, Robert W, Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N, White, Tom, Adamski, Jerzy, Bell, Jimmy D, Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T, Forgie, Ian M, Frost, Gary, Hansen, Torben, Hansen, Tue H, Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J, Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M, Teare, Harriet J A, Thomas, E Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I, Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, and Franks, Paul W

Abstract

AIMS/HYPOTHESIS: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435).METHODS: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively.RESULTS: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle.CONCLUSIONS/INTERPRETATION: These analyses partially

Published
2020

24. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Longreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstrale, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Vinuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark, I, Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, Brunak, Soren, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Longreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstrale, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Vinuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark, I, Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Soren

Abstract

Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D. Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts. Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signal

Published
2020
Full Text
View/download PDF

25. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study

Author

Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J.A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, Franks, Paul W., Koivula, Robert W., Atabaki-Pasdar, Naeimeh, Giordano, Giuseppe N., White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline, Brage, Søren, Brunak, Søren, De Masi, Federico, Dermitzakis, Emmanouil T., Forgie, Ian M., Frost, Gary, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew, Kokkola, Tarja, Kurbasic, Azra, Laakso, Markku, Mari, Andrea, McDonald, Timothy J., Pedersen, Oluf, Rutters, Femke, Schwenk, Jochen M., Teare, Harriet J.A., Thomas, E. Louise, Vinuela, Ana, Mahajan, Anubha, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Pavo, Imre, and Franks, Paul W.

Abstract

Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. Results: The TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. Conclusions/interpretation: These analyses partially suppo

Published
2020

26. Les stratégies de développement et d’écriture de la fabrique de films EuropaCorp

Author

Delon, Gaspard, Vinuela, Ana, Vanderschelden, Isabelle, Delon, Gaspard, Vinuela, Ana, and Vanderschelden, Isabelle

Abstract

Ce chapitre analyse le positionnement de la major EuropaCorp en matière de stratégies de développement de projets de films entre 2007 et 2017. Producteur et distributeur d’œuvres destinées au marché international, dont les budgets sont élevés dans le contexte du cinéma français, Luc Besson et les dirigeants d’EuropaCorp ont bien compris l’enjeu que représente le concept scénaristique dans le montage financier de leurs films. On se concentrera plus spécifiquement ici sur les différentes casquettes de Luc Besson producteur, scénariste et parfois réalisateur, dans le développement des projets destinés à un marché international. On évaluera les approches collaboratives et les équipes mobilisées pour l’élaboration de superproductions internationales qui visent un public toujours plus large, ainsi que l’efficacité des stratégies de développement de plusieurs projets de films de genre récents, dont la trilogie Taken (2008-2015), Lucy (2014) et Valérian (2017). Cela permettra d’identifier la tension entre le formatage d’un cinéma commercial et le label Besson dans les productions d’EuropaCorp, tout en questionnant les normes scénaristiques et l’originalité des pratiques d’écriture appliquées pour s’adapter aux changements du paysage cinématographique à l’ère du numérique.

Published
2020

27. Whole blood co-expression modules associate with metabolic traits and type 2 diabetes:an IMI-DIRECT study

Author

Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstrale, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Vinuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark, Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, Brunak, Søren, Gudmundsdottir, Valborg, Pedersen, Helle Krogh, Mazzoni, Gianluca, Allin, Kristine H., Artati, Anna, Beulens, Joline W., Banasik, Karina, Brorsson, Caroline, Cederberg, Henna, Chabanova, Elizaveta, De Masi, Federico, Elders, Petra J., Forgie, Ian, Giordano, Giuseppe N., Grallert, Harald, Gupta, Ramneek, Haid, Mark, Hansen, Torben, Hansen, Tue H., Hattersley, Andrew T., Heggie, Alison, Hong, Mun-Gwan, Jones, Angus G., Koivula, Robert, Kokkola, Tarja, Laakso, Markku, Løngreen, Peter, Mahajan, Anubha, Mari, Andrea, McDonald, Timothy J., McEvoy, Donna, Musholt, Petra B., Pavo, Imre, Prehn, Cornelia, Ruetten, Hartmut, Ridderstrale, Martin, Rutters, Femke, Sharma, Sapna, Slieker, Roderick C., Syed, Ali, Tajes, Juan Fernandez, Thomas, Cecilia Engel, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, Vinuela, Ana, Wesolowska-Andersen, Agata, Walker, Mark, Adamski, Jerzy, Schwenk, Jochen M., McCarthy, Mark, Pearson, Ewan, Dermitzakis, Emmanouil, Franks, Paul W., Pedersen, Oluf, and Brunak, Søren

Abstract

Background The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D. Methods Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts. Results We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signal

Published
2020

29. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium

Author

Koivula, Robert W., Forgie, Ian M., Kurbasic, Azra, Vinuela, Ana, Heggie, Alison, Giordano, Giuseppe N., Hansen, Tue H., Hudson, Michelle, Koopman, Anitra D. M., Rutters, Femke, Siloaho, Maritta, Allin, Kristine H., Brage, Soren, Brorsson, Caroline A., Dawed, Adem Y., De Masi, Federico, Groves, Christopher J., Kokkola, Tarja, Mahajan, Anubha, Perry, Mandy H., Rauh, Simone P., Ridderstrale, Martin, Teare, Harriet J. A., Thomas, E. Louise, Tura, Andrea, Vestergaard, Henrik, White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline W., Brunak, Soren, Dermitzakis, Emmanouil T., Froguel, Philippe, Frost, Gary, Gupta, Ramneek, Hansen, Torben, Hattersley, Andrew, Jablonka, Bernd, Kaye, Jane, Laakso, Markku, McDonald, Timothy J., Pedersen, Oluf, Schwenk, Jochen M., Pavo, Imre, Mari, Andrea, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, Franks, Paul W., Koivula, Robert W., Forgie, Ian M., Kurbasic, Azra, Vinuela, Ana, Heggie, Alison, Giordano, Giuseppe N., Hansen, Tue H., Hudson, Michelle, Koopman, Anitra D. M., Rutters, Femke, Siloaho, Maritta, Allin, Kristine H., Brage, Soren, Brorsson, Caroline A., Dawed, Adem Y., De Masi, Federico, Groves, Christopher J., Kokkola, Tarja, Mahajan, Anubha, Perry, Mandy H., Rauh, Simone P., Ridderstrale, Martin, Teare, Harriet J. A., Thomas, E. Louise, Tura, Andrea, Vestergaard, Henrik, White, Tom, Adamski, Jerzy, Bell, Jimmy D., Beulens, Joline W., Brunak, Soren, Dermitzakis, Emmanouil T., Froguel, Philippe, Frost, Gary, Gupta, Ramneek, Hansen, Torben, Hattersley, Andrew, Jablonka, Bernd, Kaye, Jane, Laakso, Markku, McDonald, Timothy J., Pedersen, Oluf, Schwenk, Jochen M., Pavo, Imre, Mari, Andrea, McCarthy, Mark I., Ruetten, Hartmut, Walker, Mark, Pearson, Ewan, and Franks, Paul W.

Abstract

Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up). Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe. Results: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following

Published
2019
Full Text
View/download PDF

30. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

Author

Manning, Alisa, Highland, Heather M., Gasser, Jessica, Sim, Xueling, Tukiainen, Taru, Fontanillas, Pierre, Grarup, Niels, Rivas, Manuel A., Mahajan, Anubha, Locke, Adam E., Cingolani, Pablo, Pers, Tune H., Vinuela, Ana, Brown, Andrew A., Wu, Ying, Flannick, Jason, Fuchsberger, Christian, Gamazon, Eric R., Gaulton, Kyle J., Im, Hae Kyung, Teslovich, Tanya M., Blackwell, Thomas W., Bork-Jensen, Jette, Burtt, Noel P., Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D., Perry, John R. B., Rayner, N. William, Robertson, Neil R., Scott, Laura J., van de Bunt, Martijn, Eriksson, Johan G., Jula, Antti, Koskinen, Seppo, Lehtimaki, Terho, Palotie, Aarno, Raitakari, Olli T., Jacobs, Suzanne B. R., Wessel, Jennifer, Chu, Audrey Y., Scott, Robert A., Goodarzi, Mark O., Blancher, Christine, Buck, Gemma, Buck, David, Chines, Peter S., Gabriel, Stacey, Gjesing, Anette P., Groves, Christopher J., Hollensted, Mette, Huyghe, Jeroen R., Jackson, Anne U., Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S., Stringham, Heather M., Trakalo, Joseph, Banks, Eric, Carey, Jason, Carneiro, Mauricio O., DePristo, Mark, Farjoun, Yossi, Fennell, Timothy, Goldstein, Jacqueline I., Grant, George, de Angelis, Martin Hrabe, Maguire, Jared, Neale, Benjamin M., Poplin, Ryan, Purcell, Shaun, Schwarzmayr, Thomas, Shakir, Khalid, Smith, Joshua D., Strom, Tim M., Wieland, Thomas, Lindstrom, Jaana, Brandslund, Ivan, Christensen, Cramer, Surdulescu, Gabriela L., Lakka, Timo A., Doney, Alex S. F., Nilsson, Peter, Wareham, Nicholas J., Langenberg, Claudia, Varga, Tibor V., Franks, Paul W., Rolandsson, Olov, Rosengren, Anders H., Farook, Vidya S., Thameem, Farook, Puppala, Sobha, Kumar, Satish, Lehman, Donna M., Jenkinson, Christopher P., Curran, Joanne E., Hale, Daniel Esten, Fowler, Sharon P., Arya, Rector, DeFronzo, Ralph A., Abboud, Hanna E., Syvanen, Ann-Christine, Hicks, Pamela J., Palmer, Nicholette D., Ng, Maggie C. Y., Bowden, Donald W., Freedman, Barry I., Esko, Tonu, Magi, Reedik, Milani, Lili, Mihailov, Evelin, Metspalu, Andres, Narisu, Narisu, Kinnunen, Leena, Bonnycastle, Lori L., Swift, Amy, Pasko, Dorota, Wood, Andrew R., Fadista, Joao, Pollin, Toni I., Barzilai, Nir, Atzmon, Gil, Glaser, Benjamin, Thorand, Barbara, Strauch, Konstantin, Peters, Annette, Roden, Michael, Mueller-Nurasyid, Martina, Liang, Liming, Kriebel, Jennifer, Illig, Thomas, Grallert, Harald, Gieger, Christian, Meisinger, Christa, Lannfelt, Lars, Musani, Solomon K., Griswold, Michael, Taylor, Herman A., Jr., Wilson, Gregory, Sr., Correa, Adolfo, Oksa, Heikki, Scott, William R., Afzal, Uzma, Tan, Sian-Tsung, Loh, Marie, Chambers, John C., Sehmi, Jobanpreet, Kooner, Jaspal Singh, Lehne, Benjamin, Cho, Yoon Shin, Lee, Jong-Young, Han, Bok-Ghee, Karajamaki, Annemari, Qi, Qibin, Qi, Lu, Huang, Jinyan, Hu, Frank B., Melander, Olle, Orho-Melander, Marju, Below, Jennifer E., Aguilar, David, Wong, Tien Yin, Liu, Jianjun, Khor, Chiea-Chuen, Chia, Kee Seng, Lim, Wei Yen, Cheng, Ching-Yu, Chan, Edmund, Tai, E. Shyong, Aung, Tin, Linneberg, Allan, Isomaa, Bo, Meitinger, Thomas, Tuomi, Tiinamaija, Hakaste, Liisa, Kravic, Jasmina, Jorgensen, Marit E., Lauritzen, Torsten, Deloukas, Panos, Stirrups, Kathleen E., Owen, Katharine R., Farmer, Andrew J., Frayling, Timothy M., O'Rahilly, Stephen P., Walker, Mark, Levy, Jonathan C., Hodgkiss, Dylan, Hattersley, Andrew T., Kuulasmaa, Teemu, Stancakova, Alena, Barroso, Ines, Bharadwaj, Dwaipayan, Chan, Juliana, Chandak, Giriraj R., Daly, Mark J., Donnelly, Peter J., Ebrahim, Shah B., Elliott, Paul, Fingerlin, Tasha, Froguel, Philippe, Hu, Cheng, Jia, Weiping, Ma, Ronald C. W., McVean, Gilean, Park, Taesung, Prabhakaran, Dorairaj, Sandhu, Manjinder, Scott, James, Sladek, Rob, Tandon, Nikhil, Teo, Yik Ying, Zeggini, Eleftheria, Watanabe, Richard M., Koistinen, Heikki A., Kesaniemi, Y. Antero, Uusitupa, Matti, Spector, Timothy D., Salomaa, Veikko, Rauramaa, Rainer, Palmer, Colin N. A., Prokopenko, Inga, Morris, Andrew D., Bergman, Richard N., Collins, Francis S., Lind, Lars, Ingelsson, Erik, Tuomilehto, Jaakko, Karpe, Fredrik, Groop, Leif, Jorgensen, Torben, Hansen, Torben, Pedersen, Oluf, Kuusisto, Johanna, Abecasis, GonOalo, Bell, Graeme I., Blangero, John, Cox, Nancy J., Duggirala, Ravindranath, Seielstad, Mark, Wilson, James G., Dupuis, Josee, Ripatti, Samuli, Hanis, Craig L., Florez, Jose C., Mohlke, Karen L., Meigs, James B., Laakso, Markku, Morris, Andrew P., Boehnke, Michael, Altshuler, David, McCarthy, Mark I., Gloyn, Anna L., Lindgren, Cecilia M., Manning, Alisa, Highland, Heather M., Gasser, Jessica, Sim, Xueling, Tukiainen, Taru, Fontanillas, Pierre, Grarup, Niels, Rivas, Manuel A., Mahajan, Anubha, Locke, Adam E., Cingolani, Pablo, Pers, Tune H., Vinuela, Ana, Brown, Andrew A., Wu, Ying, Flannick, Jason, Fuchsberger, Christian, Gamazon, Eric R., Gaulton, Kyle J., Im, Hae Kyung, Teslovich, Tanya M., Blackwell, Thomas W., Bork-Jensen, Jette, Burtt, Noel P., Chen, Yuhui, Green, Todd, Hartl, Christopher, Kang, Hyun Min, Kumar, Ashish, Ladenvall, Claes, Ma, Clement, Moutsianas, Loukas, Pearson, Richard D., Perry, John R. B., Rayner, N. William, Robertson, Neil R., Scott, Laura J., van de Bunt, Martijn, Eriksson, Johan G., Jula, Antti, Koskinen, Seppo, Lehtimaki, Terho, Palotie, Aarno, Raitakari, Olli T., Jacobs, Suzanne B. R., Wessel, Jennifer, Chu, Audrey Y., Scott, Robert A., Goodarzi, Mark O., Blancher, Christine, Buck, Gemma, Buck, David, Chines, Peter S., Gabriel, Stacey, Gjesing, Anette P., Groves, Christopher J., Hollensted, Mette, Huyghe, Jeroen R., Jackson, Anne U., Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S., Stringham, Heather M., Trakalo, Joseph, Banks, Eric, Carey, Jason, Carneiro, Mauricio O., DePristo, Mark, Farjoun, Yossi, Fennell, Timothy, Goldstein, Jacqueline I., Grant, George, de Angelis, Martin Hrabe, Maguire, Jared, Neale, Benjamin M., Poplin, Ryan, Purcell, Shaun, Schwarzmayr, Thomas, Shakir, Khalid, Smith, Joshua D., Strom, Tim M., Wieland, Thomas, Lindstrom, Jaana, Brandslund, Ivan, Christensen, Cramer, Surdulescu, Gabriela L., Lakka, Timo A., Doney, Alex S. F., Nilsson, Peter, Wareham, Nicholas J., Langenberg, Claudia, Varga, Tibor V., Franks, Paul W., Rolandsson, Olov, Rosengren, Anders H., Farook, Vidya S., Thameem, Farook, Puppala, Sobha, Kumar, Satish, Lehman, Donna M., Jenkinson, Christopher P., Curran, Joanne E., Hale, Daniel Esten, Fowler, Sharon P., Arya, Rector, DeFronzo, Ralph A., Abboud, Hanna E., Syvanen, Ann-Christine, Hicks, Pamela J., Palmer, Nicholette D., Ng, Maggie C. Y., Bowden, Donald W., Freedman, Barry I., Esko, Tonu, Magi, Reedik, Milani, Lili, Mihailov, Evelin, Metspalu, Andres, Narisu, Narisu, Kinnunen, Leena, Bonnycastle, Lori L., Swift, Amy, Pasko, Dorota, Wood, Andrew R., Fadista, Joao, Pollin, Toni I., Barzilai, Nir, Atzmon, Gil, Glaser, Benjamin, Thorand, Barbara, Strauch, Konstantin, Peters, Annette, Roden, Michael, Mueller-Nurasyid, Martina, Liang, Liming, Kriebel, Jennifer, Illig, Thomas, Grallert, Harald, Gieger, Christian, Meisinger, Christa, Lannfelt, Lars, Musani, Solomon K., Griswold, Michael, Taylor, Herman A., Jr., Wilson, Gregory, Sr., Correa, Adolfo, Oksa, Heikki, Scott, William R., Afzal, Uzma, Tan, Sian-Tsung, Loh, Marie, Chambers, John C., Sehmi, Jobanpreet, Kooner, Jaspal Singh, Lehne, Benjamin, Cho, Yoon Shin, Lee, Jong-Young, Han, Bok-Ghee, Karajamaki, Annemari, Qi, Qibin, Qi, Lu, Huang, Jinyan, Hu, Frank B., Melander, Olle, Orho-Melander, Marju, Below, Jennifer E., Aguilar, David, Wong, Tien Yin, Liu, Jianjun, Khor, Chiea-Chuen, Chia, Kee Seng, Lim, Wei Yen, Cheng, Ching-Yu, Chan, Edmund, Tai, E. Shyong, Aung, Tin, Linneberg, Allan, Isomaa, Bo, Meitinger, Thomas, Tuomi, Tiinamaija, Hakaste, Liisa, Kravic, Jasmina, Jorgensen, Marit E., Lauritzen, Torsten, Deloukas, Panos, Stirrups, Kathleen E., Owen, Katharine R., Farmer, Andrew J., Frayling, Timothy M., O'Rahilly, Stephen P., Walker, Mark, Levy, Jonathan C., Hodgkiss, Dylan, Hattersley, Andrew T., Kuulasmaa, Teemu, Stancakova, Alena, Barroso, Ines, Bharadwaj, Dwaipayan, Chan, Juliana, Chandak, Giriraj R., Daly, Mark J., Donnelly, Peter J., Ebrahim, Shah B., Elliott, Paul, Fingerlin, Tasha, Froguel, Philippe, Hu, Cheng, Jia, Weiping, Ma, Ronald C. W., McVean, Gilean, Park, Taesung, Prabhakaran, Dorairaj, Sandhu, Manjinder, Scott, James, Sladek, Rob, Tandon, Nikhil, Teo, Yik Ying, Zeggini, Eleftheria, Watanabe, Richard M., Koistinen, Heikki A., Kesaniemi, Y. Antero, Uusitupa, Matti, Spector, Timothy D., Salomaa, Veikko, Rauramaa, Rainer, Palmer, Colin N. A., Prokopenko, Inga, Morris, Andrew D., Bergman, Richard N., Collins, Francis S., Lind, Lars, Ingelsson, Erik, Tuomilehto, Jaakko, Karpe, Fredrik, Groop, Leif, Jorgensen, Torben, Hansen, Torben, Pedersen, Oluf, Kuusisto, Johanna, Abecasis, GonOalo, Bell, Graeme I., Blangero, John, Cox, Nancy J., Duggirala, Ravindranath, Seielstad, Mark, Wilson, James G., Dupuis, Josee, Ripatti, Samuli, Hanis, Craig L., Florez, Jose C., Mohlke, Karen L., Meigs, James B., Laakso, Markku, Morris, Andrew P., Boehnke, Michael, Altshuler, David, McCarthy, Mark I., Gloyn, Anna L., and Lindgren, Cecilia M.

Abstract

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.

Published
2017
Full Text
View/download PDF

33. Telomere length in circulating leukocytes is associated with lung function and disease

Author

Albrecht, Eva, Sillanpaa, Elina, Karrasch, Stefan, Alves, Alexessander Couto, Codd, Veryan, Hovatta, Iiris, Buxton, Jessica L., Nelson, Christopher P., Broer, Linda, Hägg, Sara, Mangino, Massimo, Willemsen, Gonneke, Surakka, Ida, Ferreira, Manuel A. R., Amin, Najaf, Oostra, Ben A., Backmand, Hell M., Peltonen, Markku, Sarna, Seppo, Rantanen, Taina, Sipila, Sarianna, Korhonen, Tellervo, Madden, Pamela A. F., Gieger, Christian, Jorres, Rudolf A., Heinrich, Joachim, Behr, Juergen, Huber, Rudolf M., Peters, Annette, Strauch, Konstantin, Wichmann, H. Erich, Waldenberger, Melanie, Blakemore, Alexandra I. F., de Geus, Eco J. C., Nyholt, Dale R., Henders, Anjali K., Piirila, Paeivi L., Rissanen, Aila, Magnusson, Patrik K. E., Vinuela, Ana, Pietilainen, Kirsi H., Martin, Nicholas G., Pedersen, Nancy L., Boomsma, Dorret I., Spector, Tim D., van Duijn, Cornelia M., Kaprio, Jaakko, Samani, Nilesh J., Jarvelin, Marjo-Riitta, Schulz, Holger, Albrecht, Eva, Sillanpaa, Elina, Karrasch, Stefan, Alves, Alexessander Couto, Codd, Veryan, Hovatta, Iiris, Buxton, Jessica L., Nelson, Christopher P., Broer, Linda, Hägg, Sara, Mangino, Massimo, Willemsen, Gonneke, Surakka, Ida, Ferreira, Manuel A. R., Amin, Najaf, Oostra, Ben A., Backmand, Hell M., Peltonen, Markku, Sarna, Seppo, Rantanen, Taina, Sipila, Sarianna, Korhonen, Tellervo, Madden, Pamela A. F., Gieger, Christian, Jorres, Rudolf A., Heinrich, Joachim, Behr, Juergen, Huber, Rudolf M., Peters, Annette, Strauch, Konstantin, Wichmann, H. Erich, Waldenberger, Melanie, Blakemore, Alexandra I. F., de Geus, Eco J. C., Nyholt, Dale R., Henders, Anjali K., Piirila, Paeivi L., Rissanen, Aila, Magnusson, Patrik K. E., Vinuela, Ana, Pietilainen, Kirsi H., Martin, Nicholas G., Pedersen, Nancy L., Boomsma, Dorret I., Spector, Tim D., van Duijn, Cornelia M., Kaprio, Jaakko, Samani, Nilesh J., Jarvelin, Marjo-Riitta, and Schulz, Holger

Abstract

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Published
2014
Full Text
View/download PDF

34. An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

Author

Yuan, Wei, Xia, Yudong, Bell, Christopher G., Yet, Idil, Ferreira, Teresa, Ward, Kirsten J., Gao, Fei, Loomis, A. Katrina, Hyde, Craig L., Wu, Honglong, Lu, Hanlin, Liu, Yuan, Small, Kerrin S., Vinuela, Ana, Morris, Andrew P., Berdasco, Maria, Esteller, Manel, Brosnan, M. Julia, Deloukas, Panos, McCarthy, Mark I., John, Sally L., Bell, Jordana T., Wang, Jun, Spector, Tim D., Yuan, Wei, Xia, Yudong, Bell, Christopher G., Yet, Idil, Ferreira, Teresa, Ward, Kirsten J., Gao, Fei, Loomis, A. Katrina, Hyde, Craig L., Wu, Honglong, Lu, Hanlin, Liu, Yuan, Small, Kerrin S., Vinuela, Ana, Morris, Andrew P., Berdasco, Maria, Esteller, Manel, Brosnan, M. Julia, Deloukas, Panos, McCarthy, Mark I., John, Sally L., Bell, Jordana T., Wang, Jun, and Spector, Tim D.

Published
2014

35. Teaching documentary: Between academia and the media industry

Author

Ana Vinuela, Centre D'Etude et de Recherche Interdisciplinaire de l'UFR LAC (CERILAC (EA_4410)), Université Paris Diderot - Paris 7 (UPD7), and Vinuela, Ana

Subjects
représentation, representation, 4. Education, media_common.quotation_subject, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, industrie audiovisuelle, General Engineering, Media industry, transmission, Art history, lcsh:Visual arts, Art, lcsh:N1-9211, 16. Peace & justice, documentaire de création, teaching documentary, creative documentary, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, media industry, enseignement du documentaire, Humanities, ComputingMilieux_MISCELLANEOUS, media_common
Abstract

Cet article s’intéresse à l’articulation entre plusieurs approches contemporaines de l’enseignement du documentaire et les conditions de la production et de la diffusion de ce type d’œuvres dans différents contextes nationaux. L’analyse de trois formations en Espagne, aux États-Unis et à Cuba soulève la question de la tension générée par la double filiation du documentaire avec le cinéma et les médias et met en évidence des formes singulières d’interdépendance entre le monde académique et l’industrie. Nous examinons des approches pédagogiques qui, associant théorie et pratique, interrogent et traversent les frontières entre disciplines, entre champs culturels et médiatiques et entre techniques de production et de diffusion. This article focuses on the relationship between different contemporary approaches to teaching documentary and the conditions of production and distribution of non-fiction in specific national contexts. The analysis of three programs in Spain, the United States and Cuba will allow us to assess the tension resulting from the double affiliation of documentary with both film and media and show singular forms of interdependence between the academic world and the industry. We will examine pedagogical approaches that, merging theory with practice, interrogate and cross the boundaries between academic fields, media and cultural categories as well as production and distribution techniques.

Published
2015

36. Correction to: The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Author

Koivula RW, Atabaki-Pasdar N, Giordano GN, White T, Adamski J, Bell JD, Beulens J, Brage S, Brunak S, De Masi F, Dermitzakis ET, Forgie IM, Frost G, Hansen T, Hansen TH, Hattersley A, Kokkola T, Kurbasic A, Laakso M, Mari A, McDonald TJ, Pedersen O, Rutters F, Schwenk JM, Teare HJA, Thomas EL, Vinuela A, Mahajan A, McCarthy MI, Ruetten H, Walker M, Pearson E, Pavo I, and Franks PW

Abstract

Unfortunately, 'Present address' was omitted from one of the addresses provided for Mark I. McCarthy (#26).

Published
2021
Full Text
View/download PDF

37. The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Author

Koivula RW, Atabaki-Pasdar N, Giordano GN, White T, Adamski J, Bell JD, Beulens J, Brage S, Brunak S, De Masi F, Dermitzakis ET, Forgie IM, Frost G, Hansen T, Hansen TH, Hattersley A, Kokkola T, Kurbasic A, Laakso M, Mari A, McDonald TJ, Pedersen O, Rutters F, Schwenk JM, Teare HJA, Thomas EL, Vinuela A, Mahajan A, McCarthy MI, Ruetten H, Walker M, Pearson E, Pavo I, and Franks PW

Subjects
Aged, Blood Glucose metabolism, Cohort Studies, Cross-Sectional Studies, Denmark epidemiology, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 therapy, Female, Finland epidemiology, Glucose Tolerance Test, Glycemic Control, Humans, Insulin Resistance, Male, Middle Aged, Netherlands epidemiology, Sweden epidemiology, Diabetes Mellitus, Type 2 metabolism, Energy Metabolism physiology, Exercise physiology, Homeostasis physiology
Abstract

Aims/hypothesis: It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435)., Methods: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively., Results: The TC and TC-PA models showed better fit than null models (TC: χ 2  = 242, p = 0.004 and χ 2  = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ 2  = 180, p = 0.041 and χ 2  = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle., Conclusions/interpretation: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results