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Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
Authors :
Huckins, Laura M. Dobbyn, Amanda Ruderfer, Douglas M. Hoffman, Gabriel Wang, Weiqing Pardinas, Antonio F. Rajagopal, Veera M. Als, Thomas D. Nguyen, Hoang T. Girdhar, Kiran Boocock, James Roussos, Panos Fromer, Menachem Kramer, Robin Domenici, Enrico Gamazon, Eric R. Purcell, Shaun Demontis, Ditte Borglum, Anders D. Walters, James T. R. O'Donovan, Michael C. Sullivan, Patrick Owen, Michael J. Devlin, Bernie Sieberts, Solveig K. Cox, Nancy J. Im, Hae Kyung Sklar, Pamela Stahl, Eli A. Johnson, Jessica S. Shah, Hardik R. Klein, Lambertus L. Dang, Kristen K. Logsdon, Benjamin A. Mahajan, Milind C. Mangravite, Lara M. Toyoshiba, Hiroyoshi Gur, Raquel E. Hahn, Chang-Gyu Schadt, Eric Lewis, David A. Haroutunian, Vahram Peters, Mette A. Lipska, Barbara K. Buxbaum, Joseph D. Hirai, Keisuke Perumal, Thanneer M. Essioux, Laurent Rajagopal, Veera Manikandan Mattheisen, Manuel Grove, Jakob Werge, Thomas Mortensen, Preben Bo Pedersen, Carsten Bocker Agerbo, Esben Pedersen, Marianne Giortz Mors, Ole Nordentoft, Merete Hougaard, David M. Bybjerg-Grauholm, Jonas Baekvad-Hansen, Marie Hansen, Christine Soholm Ripke, Stephan Neale, Benjamin M. Corvin, Aiden Farh, Kai-How Holmans, Peter A. Lee, Phil Bulik-Sullivan, Brendan Collier, David A. Huang, Hailiang Pers, Tune H. Agartz, Ingrid Albus, Margot Alexander, Madeline Amin, Farooq Bacanu, Silviu A. Begemann, Martin Belliveau, Richard A., Jr. Bene, Judit Bergen, Sarah E. Bevilacqua, Elizabeth Bigdeli, Tim B. Black, Donald W. Bruggeman, Richard Buccola, Nancy G. Buckner, Randy L. Byerley, William Cahn, Wiepke Cai, Guiqing Campion, Dominique Cantor, Rita M. Carr, Vaughan J. Carrera, Noa Catts, Stanley, V Chambert, Kimberly D. Chan, Raymond C. K. Chen, Ronald Y. L. Chen, Eric Y. H. Cheng, Wei Cheung, Eric F. C. Chong, Siow Ann Cloninger, C. Robert Cohen, David Cohen, Nadine Cormican, Paul Craddock, Nick Crowley, James J. Curtis, David Davidson, Michael Davis, Kenneth L. Degenhardt, Franziska Del Favero, Jurgen Dikeos, Dimitris Dinan, Timothy Djurovic, Srdjan Donohoe, Gary Drapeau, Elodie Duan, Jubao Dudbridge, Frank Durmishi, Naser Eichhammer, Peter Eriksson, Johan Escott-Price, Valentina Fanous, Ayman H. Farrell, Martilias S. Frank, Josef Franke, Lude Freedman, Robert Freimer, Nelson B. Friedl, Marion Friedman, Joseph, I Genovese, Giulio Georgieva, Lyudmila Giegling, Ina Giusti-Rodriguez, Paola Godard, Stephanie Goldstein, Jacqueline, I Golimbet, Vera Gopal, Srihari Gratten, Jacob de Haan, Lieuwe Hammer, Christian Hamshere, Marian L. Hansen, Mark Hansen, Thomas Hartmann, Annette M. Henskens, Frans A. Herms, Stefan Hirschhorn, Joel N. Hoffmann, Per Hofman, Andrea Hollegaard, Mads, V Ikeda, Masashi Joa, Inge Julia, Antonio Kahn, Rene S. Kalaydjieva, Luba Karachanak-Yankova, Sena Karjalainen, Juha Kavanagh, David Keller, Matthew C. Kennedy, James L. Khrunin, Andrey Kim, Yunjung Klovins, Janis Knowles, James A. Konte, Bettina Kucinskas, Vaidutis Kucinskiene, Zita Ausrele Kuzelova-Ptackova, Hana Kahler, Anna K. Laurent, Claudine Keong, Jimmy Lee Chee Lee, S. Hong Legge, Sophie E. Lerer, Bernard Li, Miaoxin Li, Tao Liang, Kung-Yee Lieberman, Jeffrey Limborska, Svetlana Loughland, Carmel M. Lubinski, Jan Lonnqvist, Jouko Macek, Milan, Jr. Magnusson, Patrik K. E. Maher, Brion S. Maier, Wolfgang Mallet, Jacques Marsal, Sara Mattingsdal, Morten McCarley, Robert W. McDonald, Colm McIntosh, Andrew M. Meier, Sandra Meijer, Carin J. Melegh, Bela Melle, Ingrid Mesholam-Gately, Raquelle, I Metspalu, Andres Michie, Patricia T. Milani, Lili Milanova, Vihra Mokrab, Younes Morris, Derek W. Murphy, Kieran C. Murray, Robin M. Myin-Germeys, Inez Muller-Myhsok, Bertram Nelis, Mari Nenadic, Igor Nertney, Deborah A. Nestadt, Gerald Nicodemus, Kristin K. Nikitina-Zake, Liene Nisenbaum, Laura Nordin Adolfsson, Annelie O'Callaghan, Eadbhard O'Dushlaine, Colm O'Neill, F. Anthony Oh, Sang-Yun Olincy, Ann Olsen, Line Van Os, Jim Pantelis, Christos Papadimitriou, George N. Papiol, Sergi Parkhomenko, Elena Pato, Michele T. Paunio, Tiina Pejovic-Milovancevic, Milica Perkins, Diana O. Pietilainen, Olli Pimm, Jonathan Pocklington, Andrew J. Powell, John Price, Alkes Pulver, Ann E. Purcell, Shaun M. Quested, Digby Rasmussen, Henrik B. Reichenberg, Abraham Reimers, Mark A. Richards, Alexander L. Roffman, Joshua L. Salomaa, Veikko Sanders, Alan R. Schall, Ulrich Schubert, Christian R. Schulze, Thomas G. Schwab, Sibylle G. Scolnick, Edward M. Scott, Rodney J. Seidman, Larry J. Shi, Jianxin Sigurdsson, Engilbert Silagadze, Teimuraz Silverman, Jeremy M. Sim, Kang Slominsky, Petr Smoller, Jordan W. So, Hon-Cheong Spencer, Chris C. A. Stefansson, Hreinn Steinberg, Stacy Stogmann, Elisabeth Straub, Richard E. Strengman, Eric Strohmaier, Jana Stroup, T. Scott Subramaniam, Mythily Suvisaari, Jaana Svrakic, Dragan M. Szatkiewicz, Jin P. Soderman, Erik Thirumalai, Srinivas Toncheva, Draga Tosato, Sarah Veijola, Juha Waddington, John Walsh, Dermot Wang, Dai Wang, Qiang Webb, Bradley T. Weiser, Mark Wildenauer, Dieter B. Williams, Nigel M. Williams, Stephanie Witt, Stephanie H. Wolen, Aaron R. Wong, Emily H. M. Wormley, Brandon K. Xi, Hualin Simon Zai, Clement C. Zheng, Xuebin Zimprich, Fritz Wray, Naomi R. Stefansson, Kari Visscher, Peter M. Adolfsson, Rolf Andreassen, Ole A. Blackwood, Douglas H. R. Bramon, Elvira Cichon, Sven Darvasi, Ariel Ehrenreich, Hannelore Esko, Tonu Gejman, Pablo, V Gill, Michael Gurling, Hugh Hultman, Christina M. Iwata, Nakao Jablensky, Assen, V Jonsson, Erik G. Kendler, Kenneth S. Kirov, George Knight, Jo Lencz, Todd Levinson, Douglas F. Li, Qingqin S. Liu, Jianjun Malhotra, Anil K. McCarroll, Steven A. McQuillin, Andrew Moran, Jennifer L. Mortensen, Preben B. Mowry, Bryan J. Nothen, Markus M. Ophoff, Roel A. Palotie, Aarno Pato, Carlos N. Petryshen, Tracey L. Posthuma, Danielle Rietschel, Marcella Riley, Brien P. Rujescu, Dan Sham, Pak C. St Clair, David Weinberger, Daniel R. Wendland, Jens R. Daly, Mark J. Sullivan, Patrick F. Huckins, Laura M. Dobbyn, Amanda Ruderfer, Douglas M. Hoffman, Gabriel Wang, Weiqing Pardinas, Antonio F. Rajagopal, Veera M. Als, Thomas D. Nguyen, Hoang T. Girdhar, Kiran Boocock, James Roussos, Panos Fromer, Menachem Kramer, Robin Domenici, Enrico Gamazon, Eric R. Purcell, Shaun Demontis, Ditte Borglum, Anders D. Walters, James T. R. O'Donovan, Michael C. Sullivan, Patrick Owen, Michael J. Devlin, Bernie Sieberts, Solveig K. Cox, Nancy J. Im, Hae Kyung Sklar, Pamela Stahl, Eli A. Johnson, Jessica S. Shah, Hardik R. Klein, Lambertus L. Dang, Kristen K. Logsdon, Benjamin A. Mahajan, Milind C. Mangravite, Lara M. Toyoshiba, Hiroyoshi Gur, Raquel E. Hahn, Chang-Gyu Schadt, Eric Lewis, David A. Haroutunian, Vahram Peters, Mette A. Lipska, Barbara K. Buxbaum, Joseph D. Hirai, Keisuke Perumal, Thanneer M. Essioux, Laurent Rajagopal, Veera Manikandan Mattheisen, Manuel Grove, Jakob Werge, Thomas Mortensen, Preben Bo Pedersen, Carsten Bocker Agerbo, Esben Pedersen, Marianne Giortz Mors, Ole Nordentoft, Merete Hougaard, David M. Bybjerg-Grauholm, Jonas Baekvad-Hansen, Marie Hansen, Christine Soholm Ripke, Stephan Neale, Benjamin M. Corvin, Aiden Farh, Kai-How Holmans, Peter A. Lee, Phil Bulik-Sullivan, Brendan Collier, David A. Huang, Hailiang Pers, Tune H. Agartz, Ingrid Albus, Margot Alexander, Madeline Amin, Farooq Bacanu, Silviu A. Begemann, Martin Belliveau, Richard A., Jr. Bene, Judit Bergen, Sarah E. Bevilacqua, Elizabeth Bigdeli, Tim B. Black, Donald W. Bruggeman, Richard Buccola, Nancy G. Buckner, Randy L. Byerley, William Cahn, Wiepke Cai, Guiqing Campion, Dominique Cantor, Rita M. Carr, Vaughan J. Carrera, Noa Catts, Stanley, V Chambert, Kimberly D. Chan, Raymond C. K. Chen, Ronald Y. L. Chen, Eric Y. H. Cheng, Wei Cheung, Eric F. C. Chong, Siow Ann Cloninger, C. Robert Cohen, David Cohen, Nadine Cormican, Paul Craddock, Nick Crowley, James J. Curtis, David Davidson, Michael Davis, Kenneth L. Degenhardt, Franziska Del Favero, Jurgen Dikeos, Dimitris Dinan, Timothy Djurovic, Srdjan Donohoe, Gary Drapeau, Elodie Duan, Jubao Dudbridge, Frank Durmishi, Naser Eichhammer, Peter Eriksson, Johan Escott-Price, Valentina Fanous, Ayman H. Farrell, Martilias S. Frank, Josef Franke, Lude Freedman, Robert Freimer, Nelson B. Friedl, Marion Friedman, Joseph, I Genovese, Giulio Georgieva, Lyudmila Giegling, Ina Giusti-Rodriguez, Paola Godard, Stephanie Goldstein, Jacqueline, I Golimbet, Vera Gopal, Srihari Gratten, Jacob de Haan, Lieuwe Hammer, Christian Hamshere, Marian L. Hansen, Mark Hansen, Thomas Hartmann, Annette M. Henskens, Frans A. Herms, Stefan Hirschhorn, Joel N. Hoffmann, Per Hofman, Andrea Hollegaard, Mads, V Ikeda, Masashi Joa, Inge Julia, Antonio Kahn, Rene S. Kalaydjieva, Luba Karachanak-Yankova, Sena Karjalainen, Juha Kavanagh, David Keller, Matthew C. Kennedy, James L. Khrunin, Andrey Kim, Yunjung Klovins, Janis Knowles, James A. Konte, Bettina Kucinskas, Vaidutis Kucinskiene, Zita Ausrele Kuzelova-Ptackova, Hana Kahler, Anna K. Laurent, Claudine Keong, Jimmy Lee Chee Lee, S. Hong Legge, Sophie E. Lerer, Bernard Li, Miaoxin Li, Tao Liang, Kung-Yee Lieberman, Jeffrey Limborska, Svetlana Loughland, Carmel M. Lubinski, Jan Lonnqvist, Jouko Macek, Milan, Jr. Magnusson, Patrik K. E. Maher, Brion S. Maier, Wolfgang Mallet, Jacques Marsal, Sara Mattingsdal, Morten McCarley, Robert W. McDonald, Colm McIntosh, Andrew M. Meier, Sandra Meijer, Carin J. Melegh, Bela Melle, Ingrid Mesholam-Gately, Raquelle, I Metspalu, Andres Michie, Patricia T. Milani, Lili Milanova, Vihra Mokrab, Younes Morris, Derek W. Murphy, Kieran C. Murray, Robin M. Myin-Germeys, Inez Muller-Myhsok, Bertram Nelis, Mari Nenadic, Igor Nertney, Deborah A. Nestadt, Gerald Nicodemus, Kristin K. Nikitina-Zake, Liene Nisenbaum, Laura Nordin Adolfsson, Annelie O'Callaghan, Eadbhard O'Dushlaine, Colm O'Neill, F. Anthony Oh, Sang-Yun Olincy, Ann Olsen, Line Van Os, Jim Pantelis, Christos Papadimitriou, George N. Papiol, Sergi Parkhomenko, Elena Pato, Michele T. Paunio, Tiina Pejovic-Milovancevic, Milica Perkins, Diana O. Pietilainen, Olli Pimm, Jonathan Pocklington, Andrew J. Powell, John Price, Alkes Pulver, Ann E. Purcell, Shaun M. Quested, Digby Rasmussen, Henrik B. Reichenberg, Abraham Reimers, Mark A. Richards, Alexander L. Roffman, Joshua L. Salomaa, Veikko Sanders, Alan R. Schall, Ulrich Schubert, Christian R. Schulze, Thomas G. Schwab, Sibylle G. Scolnick, Edward M. Scott, Rodney J. Seidman, Larry J. Shi, Jianxin Sigurdsson, Engilbert Silagadze, Teimuraz Silverman, Jeremy M. Sim, Kang Slominsky, Petr Smoller, Jordan W. So, Hon-Cheong Spencer, Chris C. A. Stefansson, Hreinn Steinberg, Stacy Stogmann, Elisabeth Straub, Richard E. Strengman, Eric Strohmaier, Jana Stroup, T. Scott Subramaniam, Mythily Suvisaari, Jaana Svrakic, Dragan M. Szatkiewicz, Jin P. Soderman, Erik Thirumalai, Srinivas Toncheva, Draga Tosato, Sarah Veijola, Juha Waddington, John Walsh, Dermot Wang, Dai Wang, Qiang Webb, Bradley T. Weiser, Mark Wildenauer, Dieter B. Williams, Nigel M. Williams, Stephanie Witt, Stephanie H. Wolen, Aaron R. Wong, Emily H. M. Wormley, Brandon K. Xi, Hualin Simon Zai, Clement C. Zheng, Xuebin Zimprich, Fritz Wray, Naomi R. Stefansson, Kari Visscher, Peter M. Adolfsson, Rolf Andreassen, Ole A. Blackwood, Douglas H. R. Bramon, Elvira Cichon, Sven Darvasi, Ariel Ehrenreich, Hannelore Esko, Tonu Gejman, Pablo, V Gill, Michael Gurling, Hugh Hultman, Christina M. Iwata, Nakao Jablensky, Assen, V Jonsson, Erik G. Kendler, Kenneth S. Kirov, George Knight, Jo Lencz, Todd Levinson, Douglas F. Li, Qingqin S. Liu, Jianjun Malhotra, Anil K. McCarroll, Steven A. McQuillin, Andrew Moran, Jennifer L. Mortensen, Preben B. Mowry, Bryan J. Nothen, Markus M. Ophoff, Roel A. Palotie, Aarno Pato, Carlos N. Petryshen, Tracey L. Posthuma, Danielle Rietschel, Marcella Riley, Brien P. Rujescu, Dan Sham, Pak C. St Clair, David Weinberger, Daniel R. Wendland, Jens R. Daly, Mark J. Sullivan, Patrick F.
Publication Year :
2019
Abstract
Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
Details
Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234598097
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.s41588-019-0364-4