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1. HNet: Graphical Hypergeometric Networks

Author

Taskesen, Erdogan

Subjects
Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

Motivation: Real-world data often contain measurements with both continuous and discrete values. Despite the availability of many libraries, data sets with mixed data types require intensive pre-processing steps, and it remains a challenge to describe the relationships between variables. The data understanding phase is an important step in the data mining process, however, without making any assumptions on the data, the search space is super-exponential in the number of variables. Methods: We propose graphical hypergeometric networks (HNet), a method to test associations across variables for significance using statistical inference. The aim is to determine a network using only the significant associations in order to shed light on the complex relationships across variables. HNet processes raw unstructured data sets and outputs a network that consists of (partially) directed or undirected edges between the nodes (i.e., variables). To evaluate the accuracy of HNet, we used well known data sets and in addition generated data sets with known ground truth. The performance of HNet is compared to Bayesian structure learning. Results: We demonstrate that HNet showed high accuracy and performance in the detection of node links. In the case of the Alarm data set we can demonstrate on average an MCC score of 0.33 + 0.0002 (P<1x10-6), whereas Bayesian structure learning resulted in an average MCC score of 0.52 + 0.006 (P<1x10-11), and randomly assigning edges resulted in a MCC score of 0.004 + 0.0003 (P=0.49). Conclusions: HNet can process raw unstructured data sets, allows analysis of mixed data types, it easily scales up in number of variables, and allows detailed examination of the detected associations. Availability: https://erdogant.github.io/hnet/, Comment: 6 pages, 4 figures

Published
2020

2. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Author

Sniekers, Suzanne, Stringer, Sven, Watanabe, Kyoko, Jansen, Philip R, Coleman, Jonathan R I, Krapohl, Eva, Taskesen, Erdogan, Hammerschlag, Anke R, Okbay, Aysu, Zabaneh, Delilah, Amin, Najaf, Breen, Gerome, Cesarini, David, Chabris, Christopher F, Iacono, William G, Ikram, M Arfan, Johannesson, Magnus, Koellinger, Philipp, Lee, James J, Magnusson, Patrik K E, McGue, Matt, Miller, Mike B, Ollier, William E R, Payton, Antony, Pendleton, Neil, Plomin, Robert, Rietveld, Cornelius A, Tiemeier, Henning, van Duijn, Cornelia M, and Posthuma, Danielle

Published
2017
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5. The value of allogeneic and autologous hematopoietic stem cell transplantation in prognostically favorable acute myeloid leukemia with double mutant CEBPA

Author

Schlenk, Richard F., Taskesen, Erdogan, van Norden, Yvette, Krauter, Jürgen, Ganser, Arnold, Bullinger, Lars, Gaidzik, Verena I., Paschka, Peter, Corbacioglu, Andrea, Göhring, Gudrun, Kündgen, Andrea, Held, Gerhard, Götze, Katharina, Vellenga, Edo, Kuball, Juergen, Schanz, Urs, Passweg, Jakob, Pabst, Thomas, Maertens, Johan, Ossenkoppele, Gert J., Delwel, Ruud, Döhner, Hartmut, Cornelissen, Jan J., Döhner, Konstanze, and Löwenberg, Bob

Published
2013
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9. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity

Author

Taskesen, Erdogan, Bullinger, Lars, Corbacioglu, Andrea, Sanders, Mathijs A., Erpelinck, Claudia A.J., Wouters, Bas J., van der Poel-van de Luytgaarde, Sonja C., Damm, Frederik, Krauter, Jürgen, Ganser, Arnold, Schlenk, Richard F., Löwenberg, Bob, Delwel, Ruud, Döhner, Hartmut, Valk, Peter J.M., and Döhner, Konstanze

Published
2011
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11. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author

Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Yang, Wu, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, James, Männikkö, Minna, Morcillo-Suarez, Carlos, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Adult Psychiatry, APH - Mental Health, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, 23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Economics, Biological Psychology, Complex Trait Genetics, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Tinbergen Institute, 23andme Research Team, Psychiatric Genomics Consortium, Social Science Genetic Association Consortium, Linner Richard Karlsson, Biroli P, Kong Edward, Meddens Fleur W., Wedow Robbee, Fontana Mark Alan, Lebreton Mael, Tino Stephen P., Abdellaoui Abdel, Hammerschlag Anke R., Nivard Michel G., Okbay Aysu, Rietveld Cornelius A., Timshel Pascal N., Trzaskowski Maciej, de Vlaming Ronald, Zund Christian L., Bao Yanchun, Buzdugan Laura, Caplin Ann H., Chen Chia-Yen, Eibich Peter, Fontanillas Pierre, Gonzalez Juan R., Joshi Peter K., Karhunen Ville, Kleinman Aaron, Levin Remy Z., Lill Christina M., Meddens Gerardus A., Muntane Gerard, Sanchez-Roige Sandra, van Rooij Frank J., Taskesen Erdogan, Wu Yang, Zhang Futao, Agee Michelle, Alipanahi Babak, Bell Robert K., Bryc Katarzyna, Elson Sarah L., Furlotte Nicholas A., Huber Karen E., Litterman Nadia K., McCreight Jennifer C., McIntyre Matthew H., Mountain Joanna L., Northover Carrie A. M., Pitts Steven J., Sathirapongsasuti J. Fah, Sazonova Olga V., Shelton Janie F., Shringarpure Suyash, Tian Chao, Tung Joyce Y., Vacic Vladimir, Wilson Catherine H., Agbessi Mawusse, Ahsan Habibul, Alves Isabel, Andiappan Anand, Awadalla Philip, Battle Alexi, Beutner Frank, Bonder Marc Jan, Boomsma Dorret I., Christiansen Mark, Claringbould Annique, Deelen Patrick, Esko Tonu, Fave Marie-Julie, Franke Lude, Frayling Timothy, Gharib Sina A., Gibson Gregory, Heijmans Bastiaan, Hemani Gibran, Jansen Rick, Kahonen Mika, Kalnapenkis Anette, Kasela Silva, Kettunen Johanne, Kim Yungil, Kirsten Holger, Kovacs Peter, Krohn Knut, Kronberg-Guzman Jaanika, Kukushkina Viktorija, Kutalik Zoltan, Lee Bernett, Lehtimaki Terho, Loeffler Marku, Marigorta Urko M., Metspalu Andre, Milani Lili, Montgomery Grant W., Mueller-Nurasyid Martina, Nauck Matthia, Penninx Brenda, Perola Marku, Pervjakova Natalia, Pierce Brandon, Powell Joseph, Prokisch Holger, Psaty Bruce M., Raitakari Olli, Ring Susan, Ripatti Samuli, Rotzchke Olaf, Rueger Sina, Saha Ashi, Scholz Marku, Schramm Katharina, Seppala Ilkka, Stumvoll Michael, Sullivan Patrick, Hoen Peter-Bramt, Teumer Alexander, Thiery Joachim, Tong Lin, Tonjes Anke, van Dongen Jenny, van Meurs Joyce, Verlouw Joost, Visscher Peter M., Voelker Uwe, Vosa Urmo, Westra Harm-Jan, Yaghootkar Hanieh, Yang Jian, Zeng Biao, Lee James J., Pers Tune H., Turley Patrick, Chen Guo-Bo, Emilsson Valur, Oskarsson Sven, Pickrell Joseph K., Thom Kevin, Timshel Pascal, Ahluwalia Tarunveer S., Bacelis Jona, Baumbach Clemen, Bjornsdottir Gyda, Brandsma Johannes H., Concas Maria Pina, Derringer Jaime, Galesloot Tessel E., Girotto Giorgia, Gupta Richa, Hall Leanne M., Harris Sarah E., Hofer Edith, Horikoshi Momoko, Huffman Jennifer E., Kaasik Kadri, Kalafati Ioanna P., Kong Augustine, Lahti Jari, van der Lee Sven J., de Leeuw Christiaan, Lind Penelope A., Lindgren Karl-Oskar, Liu Tian, Mangino Massimo, Marten Jonathan, Mihailov Evelin, Miller Michael B., van der Most Peter J., Oldmeadow Christopher, Payton Antony, Peyrot Wouter J., Qian Yong, Rueedi Rico, Salvi Erika, Schmidt Boerge, Schraut Katharina E., Shi Jianxin, Smith Albert V., Poot Raymond A., St Pourcain Beate, Thorleifsson Gudmar, Verweij Niek, Vuckovic Dragana, Wellmann Juergen, Yang Jingyun, Zhao Wei, Zhu Zhihong, Alizadeh Behrooz Z., Amin Najaf, Bakshi Andrew, Baumeister Sebastian E., Biino Ginevra, Bonnelykke Klau, Boyle Patricia A., Campbell Harry, Cappuccio Francesco P., Davies Gail, De Neve Jan-Emmanuel, Deloukas Pano, Demuth Ilja, Ding Jun, Eisele Lewin, Eklund Niina, Evans David M., Faul Jessica D., Feitosa Mary F., Forstner Andreas J., Gandin Ilaria, Gunnarsson Bjarni, Halldorsson Bjarni V., Harris Tamara B., Heath Andrew C., Hocking Lynne J., Holliday Elizabeth G., Homuth Georg, Horan Michael A., Hottenga Jouke-Jan, de Jager Philip L., Jugessur Astanand, Kaakinen Marika A., Kanoni Stavroula, Keltigangas-Jarvinen Liisa, Kiemeney Lambertus A. L. M., Kolcic Ivana, Koskinen Seppo, Kraja Aldi T., Kroh Martin, Latvala Antti, Launer Lenore J., Lebreton Mael P., Levinson Douglas F., Lichtenstein Paul, Lichtner Peter, Liewald David C. M., Loukola Anu, Madden Pamela A., Magi Reedik, Maki-Opas Tomi, Marioni Riccardo E., Marques-Vidal Pedro, McMahon George, Meisinger Christa, Meitinger Thoma, Milaneschi Yusplitri, Myhre Ronny, Nelson Christopher P., Nyholt Dale R., Ollier William E. R., Palotie Aarno, Paternoster Lavinia, Pedersen Nancy L., Petrovic Katja E., Porteous David J., Raikkonen Katri, Ring Susan M., Robino Antonietta, Rostapshova Olga, Rudan Igor, Rustichini Aldo, Salomaa Veikko, Sanders Alan R., Sarin Antti-Pekka, Schmidt Helena, Scott Rodney J., Smith Blair H., Smith Jennifer A., Staessen Jan A., Steinhagen-Thiessen Elisabeth, Strauch Konstantin, Terracciano Antonio, Tobin Martin D., Ulivi Sheila, Vaccargiu Simona, Quaye Lydia, Venturini Cristina, Vinkhuyzen Anna A. E., Voelzke Henry, Vonk Judith M., Vozzi Diego, Waage Johanne, Ware Erin B., Willemsen Gonneke, Attia John R., Bennett David A., Berger Klau, Bertram Lar, Bisgaard Han, Borecki Ingrid B., Bultmann Ute, Chabris Christopher F., Cucca Francesco, Cusi Daniele, Deary J., Dedoussis George V., van Duijn Cornelia M., Eriksson Johan G., Franke Barbara, Gasparini Paolo, Gejman Pablo V., Gieger Christian, Grabe Hans-Joergen, Gratten Jacob, Gudnason Vilmundur, van der Harst Pim, Hayward Caroline, Hinds David A., Hoffmann Wolfgang, Hypponen Elina, Iacono William G., Jacobsson Bo, Jarvelin Marjo-Riitta, Jockel Karl-Heinz, Kaprio Jaakko, Kardia Sharon L. R., Lehrer Steven F., Magnusson Patrik K. E., Martin Nicholas G., McGue Matt, Pendleton Neil, Pirastu Nicola, Pirastu Mario, Polasek Ozren, Posthuma Danielle, Power Christine, Province Michael A., Samani Nilesh J., Schlessinger David, Schmidt Reinhold, Sorensen Thorkild I. A., Spector Tim D., Stefansson Kari, Thorsteinsdottir Unnur, Thurik A. Roy, Timpson Nicholas J., Tiemeier Henning, Uitterlinden Andre G., Vitart Veronique, Vollenweider Peter, Weir David R., Wilson James F., Wright Alan F., Conley Dalton C., Krueger Robert F., Smith George Davey, Laibson David I., Medland Sarah E., Johannesson Magnu, Koellinger Philipp D., Cesarini David, Benjamin Daniel J., Auton Adam, Boardman Jason D., Clark David W., Conlin Andrew, Dolan Conor C., Fischbacher Ur, Groenen Patrick J. F., Harris Kathleen Mullan, Hasler Gregor, Hofman Albert, Ikram Mohammad A., Jain Sonia, Karlsson Robert, Kessler Ronald C., Kooyman Maarten, MacKillop Jame, Mannikko Minna, Morcillo-Suarez Carlo, McQueen Matthew B., Schmidt Klaus M., Smart Melissa C., Sutter Matthia, White Jon, de Wit Harriet, Fehr Ernst, Kumari Meena, Laibson David, Meyer Michelle N., Navarro Arcadi, Palmer Abraham A., Schunk Daniel, Stein Murray B., Svento Rauli, Timmers Paul R. H. J., Ursano Robert J., Wagner Gert G., Beauchamp Jonathan P., Karlsson Linnér, Richard, Biroli, Pietro, Kong, Edward, Meddens, S. Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Maël, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, Vlaming, Ronald de, Zünd, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntané, Gerard, Sanchez-Roige, Sandra, Rooij, Frank J. van, Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., Mccreight, Jennifer C., Mcintyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Metspalu, Andre, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Penninx, Brenda, Perola, Marku, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bram t, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, Dongen, Jenny van, Meurs, Joyce van, Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Beauchamp, Jonathan P., Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, de Vlaming, Ronald, Ahluwalia, Tarunveer S., Bacelis, Jona, Baumbach, Clemen, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Karlsson, Robert, Kong, Augustine, Lahti, Jari, Lee, Sven J. van der, de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., Most, Peter J. van der, Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Börge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., Pourcain, Beate St, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bønnelykke, Klau, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Pano, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldórsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Järvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Maël P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Mägi, Reedik, Mäki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, Mcmahon, George, Meisinger, Christa, Meitinger, Thoma, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Räikkönen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Völzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johanne, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klau, Bertram, Lar, Bisgaard, Han, Borecki, Ingrid B, Bültmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, Ian J., Dedoussis, George V., Duijn, Cornelia M. van, Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Jörgen, Gratten, Jacob, Groenen, Patrick J. F., Gudnason, Vilmundur, Harst, Pim van der, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hyppönen, Elina, Iacono, William G., Jacobsson, Bo, Järvelin, Marjo-Riitta, Jöckel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., Mcgue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sørensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, André G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Hofman, Albert, Laibson, David I., Medland, Sarah E., Meyer, Michelle N., Johannesson, Magnu, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Ur, Harris, Kathleen Mullan, Hasler, Gregor, Ikram, Mohammad A., Jain, Sonia, Kessler, Ronald C., Kooyman, Maarten, Mackillop, Jame, Männikkö, Minna, Morcillo-Suarez, Carlo, Mcqueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthia, White, Jon, Wit, Harriet de, Fehr, Ernst, Kumari, Meena, Laibson, David, Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Applied Economics, Hematology, Epidemiology, Urology, Department of Marketing Management, Internal Medicine, Medical Informatics, Cell biology, Erasmus MC other, Molecular Genetics, Econometrics, Child and Adolescent Psychiatry / Psychology, Radiology & Nuclear Medicine, Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, RS: Carim - V02 Hypertension and target organ damage, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Public Health Research (PHR), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Linnér, Richard Karlsson, Biroli , Pietro, Meddens, S Fleur W, and Beauchamp, Jonathan P

Subjects
Netherlands Twin Register (NTR), Male, LD, Medizin, Poison control, Genome-wide association study, DETERMINANTS, Cathie Marsh Institute, PREFERENCES, Q1, Genome-wide association studies, HV, 0302 clinical medicine, Genetics, Behavioral/methods, GWAS, Genetics & Heredity, Genetics, 0303 health sciences, PERSONALITY, Genetic Predisposition to Disease/genetics, Behavior/physiology, Polymorphism, Single Nucleotide/genetics, 3. Good health, Manchester Institute for Collaborative Research on Ageing, Meta-analysis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genetic Loci/genetics, Behavioural genetics, Genome-Wide Association Study/methods, Medical genetics, Female, Life Sciences & Biomedicine, Single Nucleotide/genetics, medicine.medical_specialty, ResearchInstitutes_Networks_Beacons/MICRA, Genotype, Single-nucleotide polymorphism, Genetics, Behavioral, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:330, medicine, GENDER-DIFFERENCES, SNP, Humans, Genetic Predisposition to Disease, Polymorphism, behavioural genetics, Behavioral/methods, 030304 developmental biology, Genetic association, Behavior, Science & Technology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Data Science, Case-control study, risk tolerance, GWAS, genetic architechture, Genetic Loci, Case-Control Studies, genome-wide association studies, ResearchInstitutes_Networks_Beacons/cathie_marsh_institute, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The research was also conducted using the UK Biobank Resource under application number 11425. The study was supported by funding from the Ragnar Söderberg Foundation (E9/11 and E42/15); the Swedish Research Council (421-2013-1061); the Jan Wallander and Tom Hedelius Foundation; an ERC Consolidator Grant to Philipp Koellinger (647648 EdGe); the Pershing Square Fund of the Foundations of Human Behavior; the Open Philanthropy Project; the National Institute on Aging, National Institutes of Health through grants P01-AG005842, P01-AG005842-20S2, P30-AG012810, and T32-AG000186-23 to the National Bureau of Economic Research and R01-AG042568-02 to the University of Southern California; the government of Canada through Genome Canada and the Ontario Genomics Institute (OGI-152); and the Social Sciences and Humanities Research Council of Canada. We thank the International Cannabis Consortium, the eQTLgen Consortium, and the Psychiatric Genomics Consortium for sharing summary statistics from the GWAS of lifetime cannabis use, eQTL summary statistics, and summary statistics from the GWAS of ADHD, respectively. A full list of acknowledgments is provided in the Supplementary Note.

Published
2019
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13. HAT: Hypergeometric Analysis of Tiling-arrays with application to promoter-GeneChip data

Author

Wouters Bas J, de Ridder Jeroen, Beekman Renee, Taskesen Erdogan, Peeters Justine K, Touw Ivo P, Reinders Marcel JT, and Delwel Ruud

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Tiling-arrays are applicable to multiple types of biological research questions. Due to its advantages (high sensitivity, resolution, unbiased), the technology is often employed in genome-wide investigations. A major challenge in the analysis of tiling-array data is to define regions-of-interest, i.e., contiguous probes with increased signal intensity (as a result of hybridization of labeled DNA) in a region. Currently, no standard criteria are available to define these regions-of-interest as there is no single probe intensity cut-off level, different regions-of-interest can contain various numbers of probes, and can vary in genomic width. Furthermore, the chromosomal distance between neighboring probes can vary across the genome among different arrays. Results We have developed Hypergeometric Analysis of Tiling-arrays (HAT), and first evaluated its performance for tiling-array datasets from a Chromatin Immunoprecipitation study on chip (ChIP-on-chip) for the identification of genome-wide DNA binding profiles of transcription factor Cebpa (used for method comparison). Using this assay, we can refine the detection of regions-of-interest by illustrating that regions detected by HAT are more highly enriched for expected motifs in comparison with an alternative detection method (MAT). Subsequently, data from a retroviral insertional mutagenesis screen were used to examine the performance of HAT among different applications of tiling-array datasets. In both studies, detected regions-of-interest have been validated with (q)PCR. Conclusions We demonstrate that HAT has increased specificity for analysis of tiling-array data in comparison with the alternative method, and that it accurately detects regions-of-interest in two different applications of tiling-arrays. HAT has several advantages over previous methods: i) as there is no single cut-off level for probe-intensity, HAT can detect regions-of-interest at various thresholds, ii) it can detect regions-of-interest of any size, iii) it is independent of probe-resolution across the genome, and across tiling-array platforms and iv) it employs a single user defined parameter: the significance level. Regions-of-interest are detected by computing the hypergeometric-probability, while controlling the Family Wise Error. Furthermore, the method does not require experimental replicates, common regions-of-interest are indicated, a sequence-of-interest can be examined for every detected region-of-interest, and flanking genes can be reported.

Published
2010
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14. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

Author

Linner, Richard Karlsson, Biroli, Pietro, Kong, Edward, Meddens, Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Mael, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, de Vlaming, Ronald, Zund, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntane, Gerard, Sanchez-Roige, Sandra, van Rooij, Frank J., Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawusse, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tonu, Fave, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kahonen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimaki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Mueller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rueger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppala, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bramt, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tonjes, Anke, van Dongen, Jenny, van Meurs, Joyce, Verlouw, Joost, Visscher, Peter M., Voelker, Uwe, Vosa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Kong, Augustine, Lahti, Jari, van der Lee, Sven J., de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., van der Most, Peter J., Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Boerge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., St Pourcain, Beate, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bonnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldorsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Jarvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Mael P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Magi, Reedik, Maki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, McMahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Raikkonen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Voelzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B., Bultmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, J., Dedoussis, George V., van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Joergen, Gratten, Jacob, Gudnason, Vilmundur, van der Harst, Pim, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hypponen, Elina, Iacono, William G., Jacobsson, Bo, Jarvelin, Marjo-Riitta, Jockel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., McGue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sorensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, Andre G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Laibson, David I., Medland, Sarah E., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Groenen, Patrick J. F., Harris, Kathleen Mullan, Hasler, Gregor, Hofman, Albert, Ikram, Mohammad A., Jain, Sonia, Karlsson, Robert, Kessler, Ronald C., Kooyman, Maarten, MacKillop, James, Mannikko, Minna, Morcillo-Suarez, Carlos, McQueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, de Wit, Harriet, Fehr, Ernst, Kumari, Meena, Laibson, David, Meyer, Michelle N., Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., Beauchamp, Jonathan P., Linner, Richard Karlsson, Biroli, Pietro, Kong, Edward, Meddens, Fleur W., Wedow, Robbee, Fontana, Mark Alan, Lebreton, Mael, Tino, Stephen P., Abdellaoui, Abdel, Hammerschlag, Anke R., Nivard, Michel G., Okbay, Aysu, Rietveld, Cornelius A., Timshel, Pascal N., Trzaskowski, Maciej, de Vlaming, Ronald, Zund, Christian L., Bao, Yanchun, Buzdugan, Laura, Caplin, Ann H., Chen, Chia-Yen, Eibich, Peter, Fontanillas, Pierre, Gonzalez, Juan R., Joshi, Peter K., Karhunen, Ville, Kleinman, Aaron, Levin, Remy Z., Lill, Christina M., Meddens, Gerardus A., Muntane, Gerard, Sanchez-Roige, Sandra, van Rooij, Frank J., Taskesen, Erdogan, Wu, Yang, Zhang, Futao, Agee, Michelle, Alipanahi, Babak, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Furlotte, Nicholas A., Huber, Karen E., Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., Mountain, Joanna L., Northover, Carrie A. M., Pitts, Steven J., Sathirapongsasuti, J. Fah, Sazonova, Olga V., Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce Y., Vacic, Vladimir, Wilson, Catherine H., Agbessi, Mawusse, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Bonder, Marc Jan, Boomsma, Dorret I., Christiansen, Mark, Claringbould, Annique, Deelen, Patrick, Esko, Tonu, Fave, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Gregory, Heijmans, Bastiaan, Hemani, Gibran, Jansen, Rick, Kahonen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg-Guzman, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimaki, Terho, Loeffler, Markus, Marigorta, Urko M., Metspalu, Andres, Milani, Lili, Montgomery, Grant W., Mueller-Nurasyid, Martina, Nauck, Matthias, Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon, Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli, Ring, Susan, Ripatti, Samuli, Rotzchke, Olaf, Rueger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppala, Ilkka, Stumvoll, Michael, Sullivan, Patrick, Hoen, Peter-Bramt, Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tonjes, Anke, van Dongen, Jenny, van Meurs, Joyce, Verlouw, Joost, Visscher, Peter M., Voelker, Uwe, Vosa, Urmo, Westra, Harm-Jan, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Lee, James J., Pers, Tune H., Turley, Patrick, Chen, Guo-Bo, Emilsson, Valur, Oskarsson, Sven, Pickrell, Joseph K., Thom, Kevin, Timshel, Pascal, Ahluwalia, Tarunveer S., Bacelis, Jonas, Baumbach, Clemens, Bjornsdottir, Gyda, Brandsma, Johannes H., Concas, Maria Pina, Derringer, Jaime, Galesloot, Tessel E., Girotto, Giorgia, Gupta, Richa, Hall, Leanne M., Harris, Sarah E., Hofer, Edith, Horikoshi, Momoko, Huffman, Jennifer E., Kaasik, Kadri, Kalafati, Ioanna P., Kong, Augustine, Lahti, Jari, van der Lee, Sven J., de Leeuw, Christiaan, Lind, Penelope A., Lindgren, Karl-Oskar, Liu, Tian, Mangino, Massimo, Marten, Jonathan, Mihailov, Evelin, Miller, Michael B., van der Most, Peter J., Oldmeadow, Christopher, Payton, Antony, Peyrot, Wouter J., Qian, Yong, Rueedi, Rico, Salvi, Erika, Schmidt, Boerge, Schraut, Katharina E., Shi, Jianxin, Smith, Albert V., Poot, Raymond A., St Pourcain, Beate, Thorleifsson, Gudmar, Verweij, Niek, Vuckovic, Dragana, Wellmann, Juergen, Yang, Jingyun, Zhao, Wei, Zhu, Zhihong, Alizadeh, Behrooz Z., Amin, Najaf, Bakshi, Andrew, Baumeister, Sebastian E., Biino, Ginevra, Bonnelykke, Klaus, Boyle, Patricia A., Campbell, Harry, Cappuccio, Francesco P., Davies, Gail, De Neve, Jan-Emmanuel, Deloukas, Panos, Demuth, Ilja, Ding, Jun, Eisele, Lewin, Eklund, Niina, Evans, David M., Faul, Jessica D., Feitosa, Mary F., Forstner, Andreas J., Gandin, Ilaria, Gunnarsson, Bjarni, Halldorsson, Bjarni V., Harris, Tamara B., Heath, Andrew C., Hocking, Lynne J., Holliday, Elizabeth G., Homuth, Georg, Horan, Michael A., Hottenga, Jouke-Jan, de Jager, Philip L., Jugessur, Astanand, Kaakinen, Marika A., Kanoni, Stavroula, Keltigangas-Jarvinen, Liisa, Kiemeney, Lambertus A. L. M., Kolcic, Ivana, Koskinen, Seppo, Kraja, Aldi T., Kroh, Martin, Latvala, Antti, Launer, Lenore J., Lebreton, Mael P., Levinson, Douglas F., Lichtenstein, Paul, Lichtner, Peter, Liewald, David C. M., Loukola, Anu, Madden, Pamela A., Magi, Reedik, Maki-Opas, Tomi, Marioni, Riccardo E., Marques-Vidal, Pedro, McMahon, George, Meisinger, Christa, Meitinger, Thomas, Milaneschi, Yusplitri, Myhre, Ronny, Nelson, Christopher P., Nyholt, Dale R., Ollier, William E. R., Palotie, Aarno, Paternoster, Lavinia, Pedersen, Nancy L., Petrovic, Katja E., Porteous, David J., Raikkonen, Katri, Ring, Susan M., Robino, Antonietta, Rostapshova, Olga, Rudan, Igor, Rustichini, Aldo, Salomaa, Veikko, Sanders, Alan R., Sarin, Antti-Pekka, Schmidt, Helena, Scott, Rodney J., Smith, Blair H., Smith, Jennifer A., Staessen, Jan A., Steinhagen-Thiessen, Elisabeth, Strauch, Konstantin, Terracciano, Antonio, Tobin, Martin D., Ulivi, Sheila, Vaccargiu, Simona, Quaye, Lydia, Venturini, Cristina, Vinkhuyzen, Anna A. E., Voelzke, Henry, Vonk, Judith M., Vozzi, Diego, Waage, Johannes, Ware, Erin B., Willemsen, Gonneke, Attia, John R., Bennett, David A., Berger, Klaus, Bertram, Lars, Bisgaard, Hans, Borecki, Ingrid B., Bultmann, Ute, Chabris, Christopher F., Cucca, Francesco, Cusi, Daniele, Deary, J., Dedoussis, George V., van Duijn, Cornelia M., Eriksson, Johan G., Franke, Barbara, Gasparini, Paolo, Gejman, Pablo V., Gieger, Christian, Grabe, Hans-Joergen, Gratten, Jacob, Gudnason, Vilmundur, van der Harst, Pim, Hayward, Caroline, Hinds, David A., Hoffmann, Wolfgang, Hypponen, Elina, Iacono, William G., Jacobsson, Bo, Jarvelin, Marjo-Riitta, Jockel, Karl-Heinz, Kaprio, Jaakko, Kardia, Sharon L. R., Lehrer, Steven F., Magnusson, Patrik K. E., Martin, Nicholas G., McGue, Matt, Pendleton, Neil, Pirastu, Nicola, Pirastu, Mario, Polasek, Ozren, Posthuma, Danielle, Power, Christine, Province, Michael A., Samani, Nilesh J., Schlessinger, David, Schmidt, Reinhold, Sorensen, Thorkild I. A., Spector, Tim D., Stefansson, Kari, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Tiemeier, Henning, Uitterlinden, Andre G., Vitart, Veronique, Vollenweider, Peter, Weir, David R., Wilson, James F., Wright, Alan F., Conley, Dalton C., Krueger, Robert F., Smith, George Davey, Laibson, David I., Medland, Sarah E., Johannesson, Magnus, Koellinger, Philipp D., Cesarini, David, Benjamin, Daniel J., Auton, Adam, Boardman, Jason D., Clark, David W., Conlin, Andrew, Dolan, Conor C., Fischbacher, Urs, Groenen, Patrick J. F., Harris, Kathleen Mullan, Hasler, Gregor, Hofman, Albert, Ikram, Mohammad A., Jain, Sonia, Karlsson, Robert, Kessler, Ronald C., Kooyman, Maarten, MacKillop, James, Mannikko, Minna, Morcillo-Suarez, Carlos, McQueen, Matthew B., Schmidt, Klaus M., Smart, Melissa C., Sutter, Matthias, White, Jon, de Wit, Harriet, Fehr, Ernst, Kumari, Meena, Laibson, David, Meyer, Michelle N., Navarro, Arcadi, Palmer, Abraham A., Schunk, Daniel, Stein, Murray B., Svento, Rauli, Timmers, Paul R. H. J., Ursano, Robert J., Wagner, Gert G., and Beauchamp, Jonathan P.

Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated (vertical bar(r) over cap (g)vertical bar similar to 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Published
2019

18. Erratum: Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Author

Sniekers, Suzanne, primary, Stringer, Sven, additional, Watanabe, Kyoko, additional, Jansen, Philip R, additional, Coleman, Jonathan R I, additional, Krapohl, Eva, additional, Taskesen, Erdogan, additional, Hammerschlag, Anke R, additional, Okbay, Aysu, additional, Zabaneh, Delilah, additional, Amin, Najaf, additional, Breen, Gerome, additional, Cesarini, David, additional, Chabris, Christopher F, additional, Iacono, William G, additional, Ikram, M Arfan, additional, Johannesson, Magnus, additional, Koellinger, Philipp, additional, Lee, James J, additional, Magnusson, Patrik K E, additional, McGue, Matt, additional, Miller, Mike B, additional, Ollier, William E R, additional, Payton, Antony, additional, Pendleton, Neil, additional, Plomin, Robert, additional, Rietveld, Cornelius A, additional, Tiemeier, Henning, additional, van Duijn, Cornelia M, additional, and Posthuma, Danielle, additional

Published
2017
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19. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

Author

Hammerschlag, Anke R, primary, Stringer, Sven, additional, de Leeuw, Christiaan A, additional, Sniekers, Suzanne, additional, Taskesen, Erdogan, additional, Watanabe, Kyoko, additional, Blanken, Tessa F, additional, Dekker, Kim, additional, te Lindert, Bart H W, additional, Wassing, Rick, additional, Jonsdottir, Ingileif, additional, Thorleifsson, Gudmar, additional, Stefansson, Hreinn, additional, Gislason, Thorarinn, additional, Berger, Klaus, additional, Schormair, Barbara, additional, Wellmann, Juergen, additional, Winkelmann, Juliane, additional, Stefansson, Kari, additional, Oexle, Konrad, additional, Van Someren, Eus J W, additional, and Posthuma, Danielle, additional

Published
2017
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20. Large-scale genetic study of risk tolerance and risky behaviors identifies new loci and reveals shared genetic influences

Author

Linner, Richard Karlsson, Biroli, Pietro, Fontana, Mark, Hammerschlaag, Anke, Kong, Edward, Lebreton, Mael, Meddens, Fleur, Nivard, Michel, Okbay, Aysu, Rietveld, Niels, Taskesen, Erdogan, Turley, Patrick, De Vlaming, Ronald, Wedow, Robbee, Abdellaoui, Abdel, Bao, Yanchun, Buzdugan, Laura, Chen, Chiayen, Eibich, Peter, Fontanillas, Pierre, Joshi, Peter, Karhunen, Ville, Lill, Christina, Meddens, Gerardus, Muntane, Gerard, Sanchez-roige, Sandra, Van Rooij, Frank, Stein, Murray, Auton, Adam, Clark, David, Conlin, Andrew, Dolan, Conor, Fischbacher, Urs, Groenen, Patrick, Hasler, Gregor, Hofman, Albert, Ikram, M. Arfan, Jain, Sonia, Karlsson, Robert, Mackillop, James, Mannikko, Minna, Morcillo-suarez, Carlos, Schmidt, Klaus, Smart, Melissa, Sutter, Matthias, Thurik, Roy, Uitterlinden, Andre, White, Jon, de Wit, Harriet, Bertram, Lars, Boomsma, Dorret, Fehr, Ernst, Johannesson, Magnus, Kumari, Meena, Magnusson, Patrik K. E., Navarro, Arcadi, Palmer, Abraham, Schunk, Daniel, Svento, Rauli, Tiemeier, Henning, Timmers, Paul, Ursano, Robert, Wagner, Gert, Wilson, James, Lee, James, Gratten, Jake, Laibson, David, Posthuma, Danielle, Cesarini, David, Benjamin, Daniel, Koellinger, Philipp, Beauchamp, Jonathan, Linner, Richard Karlsson, Biroli, Pietro, Fontana, Mark, Hammerschlaag, Anke, Kong, Edward, Lebreton, Mael, Meddens, Fleur, Nivard, Michel, Okbay, Aysu, Rietveld, Niels, Taskesen, Erdogan, Turley, Patrick, De Vlaming, Ronald, Wedow, Robbee, Abdellaoui, Abdel, Bao, Yanchun, Buzdugan, Laura, Chen, Chiayen, Eibich, Peter, Fontanillas, Pierre, Joshi, Peter, Karhunen, Ville, Lill, Christina, Meddens, Gerardus, Muntane, Gerard, Sanchez-roige, Sandra, Van Rooij, Frank, Stein, Murray, Auton, Adam, Clark, David, Conlin, Andrew, Dolan, Conor, Fischbacher, Urs, Groenen, Patrick, Hasler, Gregor, Hofman, Albert, Ikram, M. Arfan, Jain, Sonia, Karlsson, Robert, Mackillop, James, Mannikko, Minna, Morcillo-suarez, Carlos, Schmidt, Klaus, Smart, Melissa, Sutter, Matthias, Thurik, Roy, Uitterlinden, Andre, White, Jon, de Wit, Harriet, Bertram, Lars, Boomsma, Dorret, Fehr, Ernst, Johannesson, Magnus, Kumari, Meena, Magnusson, Patrik K. E., Navarro, Arcadi, Palmer, Abraham, Schunk, Daniel, Svento, Rauli, Tiemeier, Henning, Timmers, Paul, Ursano, Robert, Wagner, Gert, Wilson, James, Lee, James, Gratten, Jake, Laibson, David, Posthuma, Danielle, Cesarini, David, Benjamin, Daniel, Koellinger, Philipp, and Beauchamp, Jonathan

Published
2017

21. Examining the shared genetic architecture of risk tolerance and related behaviors

Author

Kong, Edward, Auton, Adam, Fontanillas, Pierre, Jain, Sonia, Chen, Chiayen, Stein, Murray, Bertram, Lars, Eibich, Peter, Lill, Christina, Wagner, Gert, Hammerschlaag, Anke, Posthuma, Danielle, Taskesen, Erdogan, Conlin, Andrew, Karhunen, Ville, Mannikko, Minna, Svento, Rauli, Nivard, Michel, Boomsma, Dorret, Abdellaoui, Abdel, Dolan, Conor, de Wit, Harriet, Palmer, Abraham, Mackillop, James, Sanchez-Roige, Sandra, Hofman, Albert, Ikram, M. Arfan, Tiemeier, Henning, Uitterlinden, Andre, Van Rooij, Frank, Groenen, Patrick, Thurik, Roy, Beauchamp, Jonathan, Benjamin, Daniel, Biroli, Pietro, Cesarini, David, De Vlaming, Ronald, Fontana, Mark, Karlsson, Richard, Koellinger, Philipp, Laibson, David, Lebreton, Mael, Lee, James, Meddens, Fleur, Meddens, Gerardus, Okbay, Aysu, Rietveld, Niels, Turley, Patrick, Wedow, Robbee, Gratten, Jake, Johannesson, Magnus, Karlsson, Robert, Magnusson, Patrik K. E., Bao, Yanchun, Kumari, Meena, Smart, Melissa, White, Jon, Joshi, Peter, Wilson, James, Clark, David, Buzdugan, Laura, Fehr, Ernst, Fischbacher, Urs, Hasler, Gregor, Morcillo-Suarez, Carlos, Muntane, Gerard, Navarro, Arcadi, Schmidt, Klaus, Schunk, Daniel, Sutter, Matthias, Kong, Edward, Auton, Adam, Fontanillas, Pierre, Jain, Sonia, Chen, Chiayen, Stein, Murray, Bertram, Lars, Eibich, Peter, Lill, Christina, Wagner, Gert, Hammerschlaag, Anke, Posthuma, Danielle, Taskesen, Erdogan, Conlin, Andrew, Karhunen, Ville, Mannikko, Minna, Svento, Rauli, Nivard, Michel, Boomsma, Dorret, Abdellaoui, Abdel, Dolan, Conor, de Wit, Harriet, Palmer, Abraham, Mackillop, James, Sanchez-Roige, Sandra, Hofman, Albert, Ikram, M. Arfan, Tiemeier, Henning, Uitterlinden, Andre, Van Rooij, Frank, Groenen, Patrick, Thurik, Roy, Beauchamp, Jonathan, Benjamin, Daniel, Biroli, Pietro, Cesarini, David, De Vlaming, Ronald, Fontana, Mark, Karlsson, Richard, Koellinger, Philipp, Laibson, David, Lebreton, Mael, Lee, James, Meddens, Fleur, Meddens, Gerardus, Okbay, Aysu, Rietveld, Niels, Turley, Patrick, Wedow, Robbee, Gratten, Jake, Johannesson, Magnus, Karlsson, Robert, Magnusson, Patrik K. E., Bao, Yanchun, Kumari, Meena, Smart, Melissa, White, Jon, Joshi, Peter, Wilson, James, Clark, David, Buzdugan, Laura, Fehr, Ernst, Fischbacher, Urs, Hasler, Gregor, Morcillo-Suarez, Carlos, Muntane, Gerard, Navarro, Arcadi, Schmidt, Klaus, Schunk, Daniel, and Sutter, Matthias

Published
2017

22. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits

Author

Hammerschlag, Anke R, Stringer, Sven, de Leeuw, Christiaan A, Sniekers, Suzanne, Taskesen, Erdogan, Watanabe, Kyoko, Blanken, Tessa F, Dekker, Kim, Te Lindert, Bart H W, Wassing, Rick, Jonsdottir, Ingileif, Thorleifsson, Gudmar, Stefansson, Hreinn, Gislason, Thorarinn, Berger, Klaus, Schormair, Barbara, Wellmann, Juergen, Winkelmann, Juliane, Stefansson, Kari, Oexle, Konrad, Van Someren, Eus J W, Posthuma, Danielle, Hammerschlag, Anke R, Stringer, Sven, de Leeuw, Christiaan A, Sniekers, Suzanne, Taskesen, Erdogan, Watanabe, Kyoko, Blanken, Tessa F, Dekker, Kim, Te Lindert, Bart H W, Wassing, Rick, Jonsdottir, Ingileif, Thorleifsson, Gudmar, Stefansson, Hreinn, Gislason, Thorarinn, Berger, Klaus, Schormair, Barbara, Wellmann, Juergen, Winkelmann, Juliane, Stefansson, Kari, Oexle, Konrad, Van Someren, Eus J W, and Posthuma, Danielle

Abstract

Persistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.

Published
2017
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28. Functional mapping and annotation of genetic associations with FUMA.

Author

Kyoko Watanabe, Taskesen, Erdogan, van Bochoven, Arjen, and Posthuma, Danielle

Abstract

A main challenge in genome-wide association studies (GWAS) is to pinpoint possible causal variants. Results from GWAS typically do not directly translate into causal variants because the majority of hits are in non-coding or intergenic regions, and the presence of linkage disequilibrium leads to effects being statistically spread out across multiple variants. Post-GWAS annotation facilitates the selection of most likely causal variant(s). Multiple resources are available for post-GWAS annotation, yet these can be time consuming and do not provide integrated visual aids for data interpretation. We, therefore, develop FUMA: an integrative web-based platform using information from multiple biological resources to facilitate functional annotation of GWAS results, gene prioritization and interactive visualization. FUMA accommodates positional, expression quantitative trait loci (eQTL) and chromatin interaction mappings, and provides gene-based, pathway and tissue enrichment results. FUMA results directly aid in generating hypotheses that are testable in functional experiments aimed at proving causal relations. [ABSTRACT FROM AUTHOR]

Published
2017
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32. Hypergeometric analysis of tiling-array and sequence data: detection and interpretation of peaks

Author

Taskesen,Erdogan, Hoogeboezem,Remco, Delwel,Ruud, Reinders,Marcel JT, Taskesen,Erdogan, Hoogeboezem,Remco, Delwel,Ruud, and Reinders,Marcel JT

Abstract

Erdogan Taskesen,1,2 Remco Hoogeboezem,1 Ruud Delwel,1 Marcel JT Reinders2,3 1Department of Hematology, Erasmus University Medical Center, Rotterdam, 2Delft Bioinformatics Lab (DBL), Delft University of Technology, Delft, 3Netherlands Bioinformatics Centre (NBIC), Nijmegen, The Netherlands Abstract: Probing protein-deoxyribonucleic acid (DNA) is gaining popularity as it sheds light on molecular mechanisms that regulate the expression of genes. Currently, tiling-arrays and next-generation sequencing technology can be used to measure these interactions. Both methods generate a signal over the genome in which contiguous regions of peaks on the genome represent the presence of an interacting molecule. Many methods do exist to identify functional regions of interest (ROIs) on the genome. However the detection of ROIs are often not an end-point in research questions and it therefore requires data dragging between tools to relate the ROIs to information present in databases, such as gene-ontology, pathway information, or enrichment of certain genomic content. We introduce hypergeometric analysis of tiling-array and sequence data (HATSEQ), a powerful tool that accurately identifies functional ROIs on the genome where a genomic signal significantly deviates from the general genome-wide behavior. HATSEQ also includes a number of built-in post-analyses with which biological meaning can be attached to the detected ROIs in terms of gene pathways and de-novo motif analysis, and provides different visualizations and statistical summaries for the detected ROIs. In addition, HATSEQ has an intuitive graphic user interface that lowers the barrier for researchers to analyze their data without the need of scripting languages. We compared the results of HATSEQ against two other popular chromatin immunoprecipitation sequencing (ChIP-Seq) methods and observed overlap in the detected ROIs but HATSEQ is more specific in delineating the peak boundaries. We also discuss the versatility of HATS

Published
2013

33. Retroviral Integration Mutagenesis in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression as a Prognostic Indicator

Author

Beekman, Renee, Valkhof, Marijke, Erkeland, Stefan, Taskesen, Erdogan, Rockova, Veronika, Peeters, Justine, Valk, Peter, Löwenberg, Bob, Touw, Ivo, Beekman, Renee, Valkhof, Marijke, Erkeland, Stefan, Taskesen, Erdogan, Rockova, Veronika, Peeters, Justine, Valk, Peter, Löwenberg, Bob, and Touw, Ivo

Abstract

Acute myeloid leukemia (AML) results from multiple genetic and epigenetic aberrations, many of which remain unidentified. Frequent loss of large chromosomal regions marks haplo-insufficiency as one of the major mechanisms contributing to leukemogenesis. However, which haplo-insufficient genes (HIGs) are involved in leukemogenesis is largely unknown and powerful experimental strategies aimed at their identification are currently lacking. Here, we present a new approach to discover HIGs, using retroviral integration mutagenesis in mice in which methylated viral integration sites and neighbouring genes were identified. In total we mapped 6 genes which are flanked by methylated viral integration sites (mVIS). Three of these, i.e., Lrmp, Hcls1 and Prkrir, were up regulated and one, i.e., Ptp4a3, was down regulated in the affected tumor. Next, we investigated the role of PTP4A3 in human AML and we show that PTP4A3 expression is a negative prognostic indicator, independent of other prognostic parameters. In conclusion, our novel strategy has identified PTP4A3 to potentially have a role in AML, on one hand as a candidate HIG contributing to leukemogenesis in mice and on the other hand as a prognostic indicator in human AML.

Published
2011

38. Loss of RAF Kinase Inhibitor Protein Is a Frequent Event In Acute Myeloid Leukemia with a Monocytic Phenotype and Cooperates with Mutant RAS In Malignant Transformation

Author

Zebisch, Armin, primary, Woelfler, Albert, additional, Hiden, Karin, additional, Bodner, Claudia, additional, Quehenberger, Franz, additional, Drasche, Astrid, additional, Pirkebner, Daniela, additional, Haller, Martina, additional, Rath, Oliver, additional, Blyth, Karen, additional, Taskesen, Erdogan, additional, Kolch, Walter, additional, Troppmair, Jakob, additional, and Sill, Heinz, additional

Published
2010
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41. Integration of gene expression and DNAmethylation profiles improves molecular subtype classification in acute myeloid leukemia.

Author

Taskesen, Erdogan, Babaei, Sepideh, Reinders, Marcel M. J., and de Ridder, Jeroen

Abstract

Background: Acute Myeloid Leukemia (AML) is characterized by various cytogenetic and molecular abnormalities. Detection of these abnormalities is important in the risk-classification of patients but requires laborious experimentation. Various studies showed that gene expression profiles (GEP), and the gene signatures derived from GEP, can be used for the prediction of subtypes in AML. Similarly, successful prediction was also achieved by exploiting DNA-methylation profiles (DMP). There are, however, no studies that compared classification accuracy and performance between GEP and DMP, neither are there studies that integrated both types of data to determine whether predictive power can be improved. Approach: Here, we used 344 well-characterized AML samples for which both gene expression and DNAmethylation profiles are available. We created three different classification strategies including early, late and no integration of these datasets and used them to predict AML subtypes using a logistic regression model with Lasso regularization. Results: We illustrate that both gene expression and DNA-methylation profiles contain distinct patterns that contribute to discriminating AML subtypes and that an integration strategy can exploit these patterns to achieve synergy between both data types. We show that concatenation of features from both data sets, i.e. early integration, improves the predictive power compared to classifiers trained on GEP or DMP alone. A more sophisticated strategy, i.e. the late integration strategy, employs a two-layer classifier which outperforms the early integration strategy. Conclusion: We demonstrate that prediction of known cytogenetic and molecular abnormalities in AML can be further improved by integrating GEP and DMP profiles. [ABSTRACT FROM AUTHOR]

Published
2015
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42. EVI1is critical for the pathogenesis of a subset of MLL-AF9–rearranged AMLs

Author

Bindels, Eric M.J., Havermans, Marije, Lugthart, Sanne, Erpelinck, Claudia, Wocjtowicz, Elizabeth, Krivtsov, Andrei V., Rombouts, Elwin, Armstrong, Scott A., Taskesen, Erdogan, Haanstra, Jurgen R., Beverloo, H. Berna, Döhner, Hartmut, Hudson, Wendy A., Kersey, John H., Delwel, Ruud, and Kumar, Ashish R.

Abstract

The proto-oncogene EVI1(ecotropic viral integration site-1), located on chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML cohort carrying 11q23 translocations, that ∼ 43% of all mixed lineage leukemia (MLL)–rearranged leukemias are EVI1pos. High EVI1expression occurs in AMLs expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELLfusion genes. In addition, we present evidence that EVI1posMLL-rearranged AMLs differ molecularly, morphologically, and immunophenotypically from EVI1negMLL-rearranged leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that MLL-AF9 fusion protein maintains Evi1expression on transformation of Evi1posHSCs. MLL-AF9 does not activate Evi1expression in MLL-AF9–transformed granulocyte macrophage progenitors (GMPs) that were initially Evi1neg. Moreover, shRNA-mediated knockdown of Evi1in an Evi1posMLL-AF9mouse model inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1provides a growth-promoting signal. Using the Evi1posMLL-AF9mouse leukemia model, we demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1expression. We conclude that EVI1is a critical player in tumor growth in a subset of MLL-rearranged AMLs.

Published
2012
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43. MiR-17/20/93/106promote hematopoietic cell expansion by targeting sequestosome 1–regulated pathways in mice

Author

Meenhuis, Annemarie, van Veelen, Peter A., de Looper, Hans, van Boxtel, Nicole, van den Berge, Iris J., Sun, Su M., Taskesen, Erdogan, Stern, Patrick, de Ru, Arnoud H., van Adrichem, Arjan J., Demmers, Jeroen, Jongen-Lavrencic, Mojca, Löwenberg, Bob, Touw, Ivo P., Sharp, Phillip A., and Erkeland, Stefan J.

Abstract

MicroRNAs (miRNAs) are pivotal for regulation of hematopoiesis but their critical targets remain largely unknown. Here, we show that ectopic expression of miR-17, -20,-93and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels. We found that these miRNAs are endogenously and abundantly expressed in myeloid progenitors and down-regulated in mature neutrophils. Quantitative proteomics identified sequestosome 1 (SQSTM1), an ubiquitin-binding protein and regulator of autophagy-mediated protein degradation, as a major target for these miRNAs in myeloid progenitors. In addition, we found increased expression of Sqstm1transcripts during CSF3-induced neutrophil differentiation of 32D-CSF3R cells and an inverse correlation of SQSTM1 protein levels and miR-106expression in AML samples. ShRNA-mediated silencing of Sqstm1phenocopied the effects of ectopic miR-17/20/93/106expression in hematopoietic progenitors in vitro and in mice. Further, SQSTM1 binds to the ligand-activated colony-stimulating factor 3 receptor (CSF3R) mainly in the late endosomal compartment, but not in LC3 positive autophagosomes. SQSTM1 regulates CSF3R stability and ligand-induced mitogen-activated protein kinase signaling. We demonstrate that AAAGUGC seed-containing miRNAs promote cell expansion, replating capacity and signaling in hematopoietic cells by interference with SQSTM1-regulated pathways.

Published
2011
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44. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPAmutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPAdouble mutant AML as a distinctive disease entity

Author

Taskesen, Erdogan, Bullinger, Lars, Corbacioglu, Andrea, Sanders, Mathijs A., Erpelinck, Claudia A.J., Wouters, Bas J., van der Poel-van de Luytgaarde, Sonja C., Damm, Frederik, Krauter, Jürgen, Ganser, Arnold, Schlenk, Richard F., Löwenberg, Bob, Delwel, Ruud, Döhner, Hartmut, Valk, Peter J.M., and Döhner, Konstanze

Abstract

We evaluated concurrent gene mutations, clinical outcome, and gene expression signatures of CCAAT/enhancer binding protein alpha (CEBPA) double mutations (CEBPAdm) versus single mutations (CEBPAsm) in 1182 cytogenetically normal acute myeloid leukemia (AML) patients (16-60 years of age). We identified 151 (12.8%) patients with CEBPAmutations (91 CEBPAdmand 60 CEBPAsm). The incidence of germline mutations was 7% (5 of 71), including 3 C-terminal mutations. CEBPAdmpatients had a lower frequency of concurrent mutations than CEBPAsmpatients (P< .0001). Both, groups were associated with a favorable outcome compared with CEBPAwt(5-year overall survival [OS] 63% and 56% vs 39%; P< .0001 and P= .05, respectively). However, in multivariable analysis only CEBPAdmwas a prognostic factor for favorable OS outcome (hazard ratio [HR] 0.36, P< .0001; event-free survival, HR 0.41, P< .0001; relapse-free survival, HR 0.55, P= .001). Outcome in CEBPAsmis dominated by concurrent NPM1and/or FLT3internal tandem duplication mutations. Unsupervised and supervised GEP analyses showed that CEBPAdmAML (n = 42), but not CEBPAsmAML (n = 18), expressed a unique gene signature. A 25-probe set prediction signature for CEBPAdmAML showed 100% sensitivity and specificity. Based on these findings, we propose that CEBPAdmshould be clearly defined from CEBPAsmAML and considered as a separate entity in the classification of AML.

Published
2011
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46. HAT: a novel statistical approach to discover functional regions in the genome.

Author

Taskesen E, Wouters B, and Delwel R

Subjects
Algorithms, Animals, Chromosome Mapping methods, Genome, Humans, Genomics methods, Oligonucleotide Array Sequence Analysis methods, Software
Abstract

Tiling arrays are useful for exploring local functions of regions of the genome in an unbiased fashion. The exact determination of those genomic regions based on tiling-array data, e.g., generated by means of hybridization with immunopreciptated DNA-fragments to the arrays is a challenge. Many different statistical methodologies have been developed to find biological relevant regions-of-interest (ROI) by using the quantitative signal intensity of each probe. We previously developed a method called Hypergeometric Analysis of Tiling arrays (HAT) for the analysis of tiling-array data, but it is developed such that it can also be used to study data derived by genome-wide deep sequencing approaches. Here we applied HAT to analyze two publicly available tiling-array data sets. After the detection of statistically significant ROI, these are often used in additional analysis for hypothesis testing. We therefore discuss, by using the results of the tiling-array experiment, pathway and motif analyses.

Published
2013
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