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1. Männlichkeiten

Author: Reif, Andrea
Abstract: Andrea Reif, Klagenfurt, Alpen-Adria-Univ., Dipl.-Arb., 2012
Published: 2012

2. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups. III. Naphthocoronene Series, Ovalene Series, and First Members of Some Higher Series

Author: Alberty, Robert A., primary, Chung, Michael B., additional, and Reif, Andrea K., additional
Published: 1990
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3. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups. II. Pyrene Series, Naphthopyrene Series, and Coronene Series.

Author: Alberty, Robert A., Chung, Michael B., and Reif, Andrea K.
Published: 1989
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4. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups I. Benzene Series.

Author: Alberty, Robert A. and Reif, Andrea K.
Published: 1988
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5. Erratum: Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups I. Benzene Series [J. Phys. Chem. Ref. Data 17, 241 (1988)].

Author: Alberty, Robert A. and Reif, Andrea K.
Published: 1989
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6. The relationship between physical and mental health: an update from the WPA Working Group on Managing Comorbidity of Mental and Physical Health

Author: Fiorillo, Andrea, de Girolamo, Giovanni, Simunovic, Ivona Filipcic, Gureje, Oye, Isaac, Mohan, Lloyd, Cathy, Mari, Jair, Patel, Vikram, Reif, Andreas, Starostina, Elena, Summergrad, Paul, Sartorius, Norman, Fiorillo, Andrea, de Girolamo, Giovanni, Simunovic, Ivona Filipcic, Gureje, Oye, Isaac, Mohan, Lloyd, Cathy, Mari, Jair, Patel, Vikram, Reif, Andrea, Starostina, Elena, Summergrad, Paul, and Sartorius, Norman
Subjects: Psychiatry and Mental health, WPA News, Pshychiatric Mental Health
Published: 2023

7. Association between polarity of first episode and solar insolation in bipolar I disorder

Author: Michael Bauer, Tasha Glenn, Eric D. Achtyes, Martin Alda, Esen Agaoglu, Kürşat Altınbaş, Ole A. Andreassen, Elias Angelopoulos, Raffaella Ardau, Memduha Aydin, Yavuz Ayhan, Christopher Baethge, Rita Bauer, Bernhard T. Baune, Ceylan Balaban, Claudia Becerra-Palars, Aniruddh P. Behere, Prakash B. Behere, Habte Belete, Tilahun Belete, Gabriel Okawa Belizario, Frank Bellivier, Robert H. Belmaker, Francesco Benedetti, Michael Berk, Yuly Bersudsky, Şule Bicakci, Harriet Birabwa-Oketcho, Thomas D. Bjella, Conan Brady, Jorge Cabrera, Marco Cappucciati, Angela Marianne Paredes Castro, Wei-Ling Chen, Eric Y.W. Cheung, Silvia Chiesa, Marie Crowe, Alessandro Cuomo, Sara Dallaspezia, Maria Del Zompo, Pratikkumar Desai, Seetal Dodd, Bruno Etain, Andrea Fagiolini, Frederike T. Fellendorf, Ewa Ferensztajn-Rochowiak, Jess G. Fiedorowicz, Kostas N. Fountoulakis, Mark A. Frye, Pierre A. Geoffroy, Ana Gonzalez-Pinto, John F. Gottlieb, Paul Grof, Bartholomeus C.M. Haarman, Hirohiko Harima, Mathias Hasse-Sousa, Chantal Henry, Lone Høffding, Josselin Houenou, Massimiliano Imbesi, Erkki T. Isometsä, Maja Ivkovic, Sven Janno, Simon Johnsen, Flávio Kapczinski, Gregory N. Karakatsoulis, Mathias Kardell, Lars Vedel Kessing, Seong Jae Kim, Barbara König, Timur L. Kot, Michael Koval, Mauricio Kunz, Beny Lafer, Mikael Landén, Erik R. Larsen, Melanie Lenger, Ute Lewitzka, Rasmus W. Licht, Carlos Lopez-Jaramillo, Alan MacKenzie, Helle Østergaard Madsen, Simone Alberte Kongstad A. Madsen, Jayant Mahadevan, Agustine Mahardika, Mirko Manchia, Wendy Marsh, Monica Martinez-Cengotitabengoa, Klaus Martiny, Yuki Mashima, Declan M. McLoughlin, Ybe Meesters, Ingrid Melle, Fátima Meza-Urzúa, Yee Ming Mok, Scott Monteith, Muthukumaran Moorthy, Gunnar Morken, Enrica Mosca, Anton A. Mozzhegorov, Rodrigo Munoz, Starlin V. Mythri, Fethi Nacef, Ravi K. Nadella, Takako Nakanotani, René Ernst Nielsen, Claire O'Donovan, Adel Omrani, Yamima Osher, Uta Ouali, Maja Pantovic-Stefanovic, Pornjira Pariwatcharakul, Joanne Petite, Andrea Pfennig, Yolanda Pica Ruiz, Marco Pinna, Maurizio Pompili, Richard Porter, Danilo Quiroz, Francisco Diego Rabelo-da-Ponte, Raj Ramesar, Natalie Rasgon, Woraphat Ratta-apha, Michaela Ratzenhofer, Maria Redahan, M.S. Reddy, Andreas Reif, Eva Z. Reininghaus, Jenny Gringer Richards, Philipp Ritter, Janusz K. Rybakowski, Leela Sathyaputri, Ângela M. Scippa, Christian Simhandl, Daniel Smith, José Smith, Paul W. Stackhouse, Dan J. Stein, Kellen Stilwell, Sergio Strejilevich, Kuan-Pin Su, Mythily Subramaniam, Ahmad Hatim Sulaiman, Kirsi Suominen, Andi J. Tanra, Yoshitaka Tatebayashi, Wen Lin Teh, Leonardo Tondo, Carla Torrent, Daniel Tuinstra, Takahito Uchida, Arne E. Vaaler, Eduard Vieta, Biju Viswanath, Maria Yoldi-Negrete, Oguz Kaan Yalcinkaya, Allan H. Young, Yosra Zgueb, Peter C. Whybrow, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Bauer, Michael, Glenn, Tasha, Achtyes, Eric D, Alda, Martin, Agaoglu, Esen, Altınbaş, Kürşat, Andreassen, Ole A, Angelopoulos, Elia, Ardau, Raffaella, Aydin, Memduha, Ayhan, Yavuz, Baethge, Christopher, Bauer, Rita, Baune, Bernhard T, Balaban, Ceylan, Becerra-Palars, Claudia, Behere, Aniruddh P, Behere, Prakash B, Belete, Habte, Belete, Tilahun, Belizario, Gabriel Okawa, Bellivier, Frank, Belmaker, Robert H, Benedetti, Francesco, Berk, Michael, Bersudsky, Yuly, Bicakci, Şule, Birabwa-Oketcho, Harriet, Bjella, Thomas D, Brady, Conan, Cabrera, Jorge, Cappucciati, Marco, Castro, Angela Marianne Parede, Chen, Wei-Ling, Cheung, Eric Y W, Chiesa, Silvia, Crowe, Marie, Cuomo, Alessandro, Dallaspezia, Sara, Del Zompo, Maria, Desai, Pratikkumar, Dodd, Seetal, Etain, Bruno, Fagiolini, Andrea, Fellendorf, Frederike T, Ferensztajn-Rochowiak, Ewa, Fiedorowicz, Jess G, Fountoulakis, Kostas N, Frye, Mark A, Geoffroy, Pierre A, Gonzalez-Pinto, Ana, Gottlieb, John F, Grof, Paul, Haarman, Bartholomeus C M, Harima, Hirohiko, Hasse-Sousa, Mathia, Henry, Chantal, Høffding, Lone, Houenou, Josselin, Imbesi, Massimiliano, Isometsä, Erkki T, Ivkovic, Maja, Janno, Sven, Johnsen, Simon, Kapczinski, Flávio, Karakatsoulis, Gregory N, Kardell, Mathia, Kessing, Lars Vedel, Kim, Seong Jae, König, Barbara, Kot, Timur L, Koval, Michael, Kunz, Mauricio, Lafer, Beny, Landén, Mikael, Larsen, Erik R, Lenger, Melanie, Lewitzka, Ute, Licht, Rasmus W, Lopez-Jaramillo, Carlo, Mackenzie, Alan, Madsen, Helle Østergaard, Madsen, Simone Alberte Kongstad A, Mahadevan, Jayant, Mahardika, Agustine, Manchia, Mirko, Marsh, Wendy, Martinez-Cengotitabengoa, Monica, Martiny, Klau, Mashima, Yuki, Mcloughlin, Declan M, Meesters, Ybe, Melle, Ingrid, Meza-Urzúa, Fátima, Mok, Yee Ming, Monteith, Scott, Moorthy, Muthukumaran, Morken, Gunnar, Mosca, Enrica, Mozzhegorov, Anton A, Munoz, Rodrigo, Mythri, Starlin V, Nacef, Fethi, Nadella, Ravi K, Nakanotani, Takako, Nielsen, René Ernst, O'Donovan, Claire, Omrani, Adel, Osher, Yamima, Ouali, Uta, Pantovic-Stefanovic, Maja, Pariwatcharakul, Pornjira, Petite, Joanne, Pfennig, Andrea, Ruiz, Yolanda Pica, Pinna, Marco, Pompili, Maurizio, Porter, Richard, Quiroz, Danilo, Rabelo-da-Ponte, Francisco Diego, Ramesar, Raj, Rasgon, Natalie, Ratta-Apha, Woraphat, Ratzenhofer, Michaela, Redahan, Maria, Reddy, M S, Reif, Andrea, Reininghaus, Eva Z, Richards, Jenny Gringer, Ritter, Philipp, Rybakowski, Janusz K, Sathyaputri, Leela, Scippa, Ângela M, Simhandl, Christian, Smith, Daniel, Smith, José, Stackhouse, Paul W, Stein, Dan J, Stilwell, Kellen, Strejilevich, Sergio, Su, Kuan-Pin, Subramaniam, Mythily, Sulaiman, Ahmad Hatim, Suominen, Kirsi, Tanra, Andi J, Tatebayashi, Yoshitaka, Teh, Wen Lin, Tondo, Leonardo, Torrent, Carla, Tuinstra, Daniel, Uchida, Takahito, Vaaler, Arne E, Vieta, Eduard, Viswanath, Biju, Yoldi-Negrete, Maria, Yalcinkaya, Oguz Kaan, Young, Allan H, Zgueb, Yosra, and Whybrow, Peter C
Subjects: Bipolar Disorder/complications, Male, Polarity, Bipolar disorder, Circadian rhythm, Depression, Psychiatry and Mental health, Clinical Psychology, Solar insolation, Sunlight, Humans, Female, Seasons
Abstract: OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
Published: 2022

8. Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends: An interrupted time series analysis in 33 countries

Author: Jane Pirkis, David Gunnell, Sangsoo Shin, Marcos Del Pozo-Banos, Vikas Arya, Pablo Analuisa Aguilar, Louis Appleby, S. M. Yasir Arafat, Ella Arensman, Jose Luis Ayuso-Mateos, Yatan Pal Singh Balhara, Jason Bantjes, Anna Baran, Chittaranjan Behera, Jose Bertolote, Guilherme Borges, Michael Bray, Petrana Brečić, Eric Caine, Raffaella Calati, Vladimir Carli, Giulio Castelpietra, Lai Fong Chan, Shu-Sen Chang, David Colchester, Maria Coss-Guzmán, David Crompton, Marko Ćurković, Rakhi Dandona, Eva De Jaegere, Diego De Leo, Eberhard A. Deisenhammer, Jeremy Dwyer, Annette Erlangsen, Jeremy S. Faust, Michele Fornaro, Sarah Fortune, Andrew Garrett, Guendalina Gentile, Rebekka Gerstner, Renske Gilissen, Madelyn Gould, Sudhir Kumar Gupta, Keith Hawton, Franziska Holz, Iurii Kamenshchikov, Navneet Kapur, Alexandr Kasal, Murad Khan, Olivia J. Kirtley, Duleeka Knipe, Kairi Kõlves, Sarah C. Kölzer, Hryhorii Krivda, Stuart Leske, Fabio Madeddu, Andrew Marshall, Anjum Memon, Ellenor Mittendorfer-Rutz, Paul Nestadt, Nikolay Neznanov, Thomas Niederkrotenthaler, Emma Nielsen, Merete Nordentoft, Herwig Oberlerchner, Rory C. O'Connor, Rainer Papsdorf, Timo Partonen, Michael R. Phillips, Steve Platt, Gwendolyn Portzky, Georg Psota, Ping Qin, Daniel Radeloff, Andreas Reif, Christine Reif-Leonhard, Mohsen Rezaeian, Nayda Román-Vázquez, Saska Roskar, Vsevolod Rozanov, Grant Sara, Karen Scavacini, Barbara Schneider, Natalia Semenova, Mark Sinyor, Stefano Tambuzzi, Ellen Townsend, Michiko Ueda, Danuta Wasserman, Roger T. Webb, Petr Winkler, Paul S.F. Yip, Gil Zalsman, Riccardo Zoja, Ann John, Matthew J. Spittal, Pirkis, Jane, Gunnell, David, Shin, Sangsoo, Del Pozo-Banos, Marco, Arya, Vika, Aguilar, Pablo Analuisa, Appleby, Loui, Arafat, S M Yasir, Arensman, Ella, Ayuso-Mateos, Jose Lui, Balhara, Yatan Pal Singh, Bantjes, Jason, Baran, Anna, Behera, Chittaranjan, Bertolote, Jose, Borges, Guilherme, Bray, Michael, Brečić, Petrana, Caine, Eric, Calati, Raffaella, Carli, Vladimir, Castelpietra, Giulio, Chan, Lai Fong, Chang, Shu-Sen, Colchester, David, Coss-Guzmán, Maria, Crompton, David, Ćurković, Marko, Dandona, Rakhi, De Jaegere, Eva, De Leo, Diego, Deisenhammer, Eberhard A, Dwyer, Jeremy, Erlangsen, Annette, Faust, Jeremy S, Fornaro, Michele, Fortune, Sarah, Garrett, Andrew, Gentile, Guendalina, Gerstner, Rebekka, Gilissen, Renske, Gould, Madelyn, Gupta, Sudhir Kumar, Hawton, Keith, Holz, Franziska, Kamenshchikov, Iurii, Kapur, Navneet, Kasal, Alexandr, Khan, Murad, Kirtley, Olivia J, Knipe, Duleeka, Kõlves, Kairi, Kölzer, Sarah C, Krivda, Hryhorii, Leske, Stuart, Madeddu, Fabio, Marshall, Andrew, Memon, Anjum, Mittendorfer-Rutz, Ellenor, Nestadt, Paul, Neznanov, Nikolay, Niederkrotenthaler, Thoma, Nielsen, Emma, Nordentoft, Merete, Oberlerchner, Herwig, O'Connor, Rory C, Papsdorf, Rainer, Partonen, Timo, Phillips, Michael R, Platt, Steve, Portzky, Gwendolyn, Psota, Georg, Qin, Ping, Radeloff, Daniel, Reif, Andrea, Reif-Leonhard, Christine, Rezaeian, Mohsen, Román-Vázquez, Nayda, Roskar, Saska, Rozanov, Vsevolod, Sara, Grant, Scavacini, Karen, Schneider, Barbara, Semenova, Natalia, Sinyor, Mark, Tambuzzi, Stefano, Townsend, Ellen, Ueda, Michiko, Wasserman, Danuta, Webb, Roger T, Winkler, Petr, Yip, Paul S F, Zalsman, Gil, Zoja, Riccardo, John, Ann, Spittal, Matthew J, Pirkis, J, Gunnell, D, Shin, S, Del Pozo-Banos, M, Arya, V, Aguilar, P, Appleby, L, Arafat, S, Arensman, E, Ayuso-Mateos, J, Balhara, Y, Bantjes, J, Baran, A, Behera, C, Bertolote, J, Borges, G, Bray, M, Brečić, P, Caine, E, Calati, R, Carli, V, Castelpietra, G, Chan, L, Chang, S, Colchester, D, Coss-Guzmán, M, Crompton, D, Ćurković, M, Dandona, R, De Jaegere, E, De Leo, D, Deisenhammer, E, Dwyer, J, Erlangsen, A, Faust, J, Fornaro, M, Fortune, S, Garrett, A, Gentile, G, Gerstner, R, Gilissen, R, Gould, M, Gupta, S, Hawton, K, Holz, F, Kamenshchikov, I, Kapur, N, Kasal, A, Khan, M, Kirtley, O, Knipe, D, Kõlves, K, Kölzer, S, Krivda, H, Leske, S, Madeddu, F, Marshall, A, Memon, A, Mittendorfer-Rutz, E, Nestadt, P, Neznanov, N, Niederkrotenthaler, T, Nielsen, E, Nordentoft, M, Oberlerchner, H, O'Connor, R, Papsdorf, R, Partonen, T, Phillips, M, Platt, S, Portzky, G, Psota, G, Qin, P, Radeloff, D, Reif, A, Reif-Leonhard, C, Rezaeian, M, Román-Vázquez, N, Roskar, S, Rozanov, V, Sara, G, Scavacini, K, Schneider, B, Semenova, N, Sinyor, M, Tambuzzi, S, Townsend, E, Ueda, M, Wasserman, D, Webb, R, Winkler, P, Yip, P, Zalsman, G, Zoja, R, John, A, and Spittal, M
Subjects: Suicide, Monitoring, Pandemic, SASH, COVID-19, Medicine and Health Sciences, General Medicine
Abstract: Background Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age-and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries' COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries' income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well. Interpretation Although there are some countries/areas-within-countries where overall suicide numbers and numbers for certain sex- and age-based groups are greater-than-expected, these countries/areas-within-countries are in the minority. Any upward movement in suicide numbers in any place or group is concerning, and we need to remain alert to and respond to changes as the pandemic and its mental health and economic consequences continue. Copyright (C) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Published: 2022

9. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: Machine learning approach

Author: Cearns, Micah, Amare, Azmeraw, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna, Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Zompo, Maria Del, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas, Frisen, Louise, Frye, Mark, Fullerton, Janice, Gard, Sébastien, Garnham, Julie, Goes, Fernando, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Urs, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael, Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis, Monteleone, Palmiero, Nievergelt, Caroline, Nöthen, Markus, Novák, Tomas, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James, Reif, Andreas, Reininghaus, Eva, Rouleau, Guy, Rybakowski, Janusz, Schalling, Martin, Schofield, Peter, Schweizer, Barbara, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire, Squassina, Alessio, Stamm, Thomas, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie, Roberts, Gloria, Zandi, Peter, Alda, Martin, Bauer, Michael, Mcmahon, Francis, Mitchell, Philip, Schulze, Thomas, Rietschel, Marcella, Clark, Scott, Baune, Bernhard, Cearns, Micah, Amare, Azmeraw T, Schubert, Klaus Oliver, Thalamuthu, Anbupalam, Frank, Joseph, Streit, Fabian, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bárbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dayer, Alexandre, Degenhardt, Franziska, Zompo, Maria Del, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisen, Louise, Frye, Mark A, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Heilbronner, Ur, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Hou, Liping, Hsu, Yi-Hsiang, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J, Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Toma, O'Donovan, Claire, Ozaki, Norio, Millischer, Vincent, Papiol, Sergi, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andrea, Reininghaus, Eva, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Schofield, Peter R, Schweizer, Barbara W, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Tekola-Ayele, Fasil, Tortorella, Alfonso, Turecki, Gustavo, Veeh, Julia, Vieta, Eduard, Witt, Stephanie H, Roberts, Gloria, Zandi, Peter P, Alda, Martin, Bauer, Michael, Mcmahon, Francis J, Mitchell, Philip B, Schulze, Thomas G, Rietschel, Marcella, Clark, Scott R, Baune, Bernhard T, Etain, Bruno, University of South Australia [Adelaide], South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, University Medical Center Heidelberg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], National Institute of Mental Health (NIMH), National Institutes of Health [Bethesda] (NIH), Dokkyo Medical University, Università degli Studi di Cagliari = University of Cagliari (UniCa), University of Barcelona, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Karolinska Institute, Karolinska University Hospital [Stockholm], University of California [San Diego] (UC San Diego), University of California (UC), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Medical University of Graz, Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, McGill University Health Center [Montreal] (MUHC), National Taiwan University [Taiwan] (NTU), University of Bonn, University Hospital Basel [Basel], Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Poznan University of Medical Sciences [Poland] (PUMS), Johns Hopkins University (JHU), Ludwig Maximilian University [Munich] (LMU), University of Basel (Unibas), Karolinska Institutet [Stockholm], University of New South Wales [Sydney] (UNSW), Centre hospitalier Charles Perrens [Bordeaux], Dalhousie University [Halifax], 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry [Bucharest, Romania], Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Osaka University [Osaka], Georg-August-University = Georg-August-Universität Göttingen, University Medical Center Göttingen (UMG), Institute of Psychiatric Phenomics and Genomics (IPPG), Ludwig-Maximilians-Universität München (LMU), Harvard School of Public Health, Harvard Medical School [Boston] (HMS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Psychothérapique de Nancy [Laxou] (CPN), Juntendo University, Frankfurt University Hospital, Landesklinikum Neunkirchen (LK Neunkirchen), Hokkaido University [Sapporo, Japan], Sahlgrenska Academy at University of Gothenburg [Göteborg], VA San Diego Healthcare System [San Diego, CA, USA] (VASDHS), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, University of Cincinnati (UC), IMIM-Hospital del Mar, Generalitat de Catalunya, Instituto de Salud Carlos III [Madrid] (ISC), Università degli Studi di Salerno = University of Salerno (UNISA), National Institute of Mental Health [Klecany, Czech Republic] (NIMH), Nagoya University, Medizinische Universität Wien = Medical University of Vienna, University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Montreal Neurological Institute and Hospital, Neuroscience Research Australia (NeuRA), Sigmund Freud University (SFU), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Università degli Studi di Perugia = University of Perugia (UNIPG), Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg], Johns Hopkins Bloomberg School of Public Health [Baltimore], University Medical Center, University of Adelaide, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University of Melbourne, and The Florey Institute of Neuroscience and Mental Health
Subjects: Psychiatry and Mental health, depressive disorder, bipolar affective disorder, outcome studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Mood stabiliser, Mood stabilisers, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, genetics, genetic, depressive disorders, bipolar affective disorders
Abstract: BackgroundResponse to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.AimsTo use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.MethodThis study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.ResultsThe best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.ConclusionsUsing PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Published: 2022

10. Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Author: Eduard Vieta, Liping Hou, Markus M. Nöthen, Martin Schalling, Thomas Stamm, Thomas G. Schulze, Norio Ozaki, Claire O'Donovan, Azmeraw T. Amare, Alessio Squassina, Alfonso Tortorella, Kazufumi Akiyama, Urs Heilbronner, Caroline M. Nievergelt, Frank Bellivier, Palmiero Monteleone, Mirko Manchia, Tadafumi Kato, Per Hoffmann, Jean-Michel Aubry, Claudia Pisanu, Pavla Stopkova, Lena Backlund, Anthony Batzler, James B. Potash, Susan L. McElroy, Jean-Pierre Kahn, Guy A. Rouleau, Bernhard T. Baune, Francis M. Mondimore, Beth Larrabee, Peter P. Zandi, Christian Simhandl, Susan G. Leckband, Andrea Pfennig, Maria Del Zompo, Francis J. McMahon, Tatyana Shekhtman, Giovanni Severino, Tomas Novak, Andreas J. Forstner, Marcella Rietschel, Paul Grof, Maria Grigoroiu-Serbanescu, Ryota Hashimoto, Nirmala Akula, Sarah Kittel-Schneider, John R. Kelsoe, Andreas Reif, Joanna M. Biernacka, Barbara W. Schweizer, Janice M. Fullerton, Sébastien Gard, Julie Garnham, Barbara König, Mark A. Frye, Michael Bauer, Po-Hsiu Kuo, Janusz K. Rybakowski, Joanna Hauser, Pablo Cervantes, Gonzalo Laje, Urban Ösby, Nina Dalkner, Ewa Ferensztajn-Rochowiak, Mikael Landén, Hsi-Chung Chen, Claire Slaney, Eva Z. Reininghaus, Katzutaka Shimoda, Esther Jiménez, Cristiana Cruceanu, Francesc Colom, Catharina Lavebratt, Abesh Kumar Bhattacharjee, Marina Mitjans, Sergi Papiol, Stephanie H. Witt, Sven Cichon, Bruno Etain, Layla Kassem, Caterina Chillotti, Fernando S. Goes, Franziska Degenhardt, J. Raymond DePaulo, Martin Alda, Ichiro Kusumi, Peter Falkai, Antoni Benabarre, Stéphane Jamain, Philip B. Mitchell, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Mario Maj, Paul D. Shilling, Mazda Adli, Louise Frisén, Brandon J. Coombes, Gustavo Turecki, Scott R. Clark, Bárbara Arias, Vincent Millischer, Michael McCarthy, Marion Leboyer, Lina Martinsson, Piotr M. Czerski, Coombes, Brandon J, Millischer, Vincent, Batzler, Anthony, Larrabee, Beth, Hou, Liping, Papiol, Sergi, Heilbronner, Ur, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Amare, Azmeraw T, Ardau, Raffaella, Arias, Barbara, Aubry, Jean-Michel, Backlund, Lena, Bauer, Michael, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Degenhardt, Franziska, Del Zompo, Maria, Depaulo, J Raymond, Étain, Bruno, Falkai, Peter, Ferensztajn-Rochowiak, Ewa, Forstner, Andreas J, Frisen, Louise, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kato, Tadafumi, Kelsoe, John R, Kittel-Schneider, Sarah, König, Barbara, Kuo, Po-Hsiu, Kusumi, Ichiro, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J, Mcelroy, Susan L, Mitchell, Philip B, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Novák, Toma, O'Donovan, Claire, Osby, Urban, Ozaki, Norio, Pfennig, Andrea, Pisanu, Claudia, Potash, James B, Reif, Andrea, Reininghaus, Eva, Rietschel, Marcella, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Schofield, Peter R, Schubert, Klaus Oliver, Schweizer, Barbara W, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M, Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Witt, Stephanie H, Zandi, Peter P, Fullerton, Janice M, Alda, Martin, Frye, Mark A, Schulze, Thomas G, Mcmahon, Francis J, and Biernacka, Joanna M
Subjects: medicine.medical_specialty, Lithium (medication), business.industry, Bipolar disorder, General Medicine, medicine.disease, Polygenic risk scores, Attention-deficit/hyperactivity disorder, Lithium response, Adherence, medicine, Attention deficit hyperactivity disorder, Association (psychology), Psychiatry, business, Depression (differential diagnoses), 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Research Article, medicine.drug
Abstract: Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
Published: 2021

11. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders:Findings from the ENIGMA ADHD, ASD, and OCD working groups

Author: Pedro Moreira, Ruth O'Gorman Tuura, Mara Cercignani, Philip Aherson, Maria Jalbrzikowski, Kate D. Fitzgerald, Declan G. Murphy, Bernd Kardatzki, Christine Ecker, David F. Tolin, Fern Jaspers-Fayer, Pedro Morgado, Juan Carlos Soliva Vila, Kang Ik K. Cho, Kathrin Koch, Timothy J. Silk, Philip R. Szeszko, Thomas Frodl, Mara Parellada, Shlomi Haar, Eileen Daly, Bob Oranje, Anouk Schrantee, Leyla Namazova-Baranova, Joseph A. King, Beatriz Luna, Silvia Brem, Eric Earl, Alasdair Vance, Michela Tosetti, Christine Deruelle, Ramona Baur-Streubel, Jackie Fitzgerald, Kirsten O'Hearn, Michael C. Stevens, Yoshiyuki Hirano, J. Antoni Ramos-Quiroga, Erika L. Nurmi, Kaylita Chantiluke, Joseph O'Neill, Kerstin Kohls, Olga Puig, Devon Shook, Clodagh M. Murphy, Gustavo Sudre, Marlene Behrmann, Jaap Oosterlaan, Tinatin Gogberashvili, Lianne Schmaal, Carles Soriano-Mas, Liesbeth Hoekstra, Ignacio Martínez-Zalacaín, Noam Soreni, Marcel P. Zwiers, Paulo Mattos, Gregor Kohls, Andreas J. Fallgatter, Tiffany M. Chaim-Avancini, Alexander Baranov, S. Evelyn Stewart, Sara Dallaspezia, Gianfranco Spalletta, Jonna Kuntsi, Lizanne J. S. Schweren, Joel T. Nigg, Leanne Tamm, Premika S.W. Boedhoe, Adriana Di Martino, Jane McGrath, Marcelo C. Batistuzzo, Norbert Skokauskas, Filippo Muratori, John Piacentini, Jean-Paul Fouche, Sarah Baumeister, Alan Anticevic, Neil A. Harrison, Christine M. Freitag, Pedro G.P. Rosa, Stephen V. Faraone, Ana Cubillo, David Mataix-Cols, Yuki Sakai, Stefan Ehrlich, Eileen Oberwelland Weiss, Fabrizio Piras, Dirk J. Heslenfeld, Je-Yeon Yun, Paul Pauli, Catharina A. Hartman, Ganesan Venkatasubramanian, Janardhanan C. Narayanaswamy, Charles B Malpas, Jan C. Beucke, José M. Menchón, Egill A. Fridgeirsson, Margot J. Taylor, Mauricio Moller Martinho, H. Blair Simpson, Jan K. Buitelaar, Gerd Kvale, Ivanei E. Bramati, Aki Tsuchiyagaito, Susanne Walitza, Irene Bollettini, Jeffery N. Epstein, Anders M. Dale, Thomas Ethofer, Terry L. Jernigan, David Coghill, Rachel Marsh, Andreas Reif, Astri J. Lundervold, Pieter J. Hoekstra, Oana Georgiana Rus, Damiaan Denys, Gregory L. Wallace, Matt C. Gabel, Hazel McCarthy, Sarah Hohmann, Rosa Nicolau, Stephanie H. Ameis, Neda Jahanshad, Takashi Nakamae, Xin Feng, Emily R. Stern, Georg G. von Polier, Yanni Liu, Paulo Marques, Anushree Bose, Hao Hu, Sara Lera-Miguel, Deniz A. Gürsel, Jochen Seitz, Jos W. R. Twisk, Mario Rodrigues Louzã, Clare Kelly, Annette Conzelmann, Alysa E. Doyle, Odile A. van den Heuvel, Anthony A. James, Chris Perriello, Joost Janssen, Damien A. Fair, Norbert Kathmann, Francisco X. Castellanos, Paul D. Arnold, Oscar Vilarroya, Geraldo F. Busatto, Federica Piras, Pino Alonso, Akiko Nakagawa, Sarah Durston, Lena Schwarz, Mitul A. Mehta, Dan J. Stein, Celso Arango, Daan van Rooij, Ilan Dinstein, Anastasia Christakou, Klaus-Peter Lesch, Kerstin J. Plessen, Jennifer Fedor, Yolanda Vives-Gilabert, Ilaria Gori, Louise Gallagher, Brian P. Brennan, Yuqi Cheng, Barbara Franke, Sabin Khadka, Stephanie E. Novotny, Martine Hoogman, Georgii Karkashadze, Georg C. Ziegler, Yuliya N. Yoncheva, Rosa Calvo, Thomas Wolfers, Marcelo Q. Hoexter, Benjamin A. Ely, Masaru Kuno, Alessandra Retico, Yoshinari Abe, Geoffrey B. Hall, Tobias Banaschewski, Anatoly Anikin, Christine Lochner, Astrid Morer, Guido van Wingen, Jan Haavik, Joseph Biederman, Luisa Lázaro, Francesco Benedetti, Fengfeng Zhou, Guillaume Auzias, Daniel Brandeis, Dmitry Kapilushniy, Katya Rubia, Philip Shaw, Christian Kaufmann, Sara Calderoni, Marcus V. Zanetti, Anastasia Solovieva, Zhen Wang, Francesca Assogna, Jamie D. Feusner, Chaim Huyser, Fernanda Tovar-Moll, Theo G.M. van Erp, Y.C. Janardhan Reddy, Jun Soo Kwon, Yannis Paloyelis, Anna Calvo, Patricia Gruner, Kathrin C. Zierhut, Liesbeth Reneman, Tomohiro Nakao, Janita Bralten, Marie F. Høvik, Mark A. Bellgrove, Maarten Mennes, Paul M. Thompson, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Epidemiology and Data Science, Pediatric surgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Boedhoe, Premika S W, van Rooij, Daan, Hoogman, Martine, Twisk, Jos W R, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobia, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thoma, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thoma, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, Kardatzki, Bernd, Karkashadze, Georgii, Kathmann, Norbert, Kaufmann, Christian, Kelly, Clare, Khadka, Sabin, King, Joseph A, Koch, Kathrin, Kohls, Gregor, Konrad, Kerstin, Kuno, Masaru, Kuntsi, Jonna, Kvale, Gerd, Kwon, Jun Soo, Lázaro, Luisa, Lera-Miguel, Sara, Lesch, Klaus-Peter, Hoekstra, Liesbeth, Liu, Yanni, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, Malpas, Charles B, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mattos, Paulo, Mccarthy, Hazel, Mcgrath, Jane, Mehta, Mitul A, Menchón, José M, Mennes, Maarten, Martinho, Mauricio Moller, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan G M, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Namazova-Baranova, Leyla, Narayanaswamy, Janardhanan C, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Nurmi, Erika L, Weiss, Eileen Oberwelland, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, O'Neill, Joseph, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yanni, Parellada, Mara, Pauli, Paul, Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Puig, Olga, Ramos-Quiroga, J Antoni, Reddy, Y C Janardhan, Reif, Andrea, Reneman, Liesbeth, Retico, Alessandra, Rosa, Pedro G P, Rubia, Katya, Rus, Oana Georgiana, Sakai, Yuki, Schrantee, Anouk, Schwarz, Lena, Schweren, Lizanne J S, Seitz, Jochen, Shaw, Philip, Shook, Devon, Silk, Tim J, Simpson, H Blair, Skokauskas, Norbert, Soliva Vila, Juan Carlo, Solovieva, Anastasia, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Sudre, Gustavo, Szeszko, Philip R, Tamm, Leanne, Taylor, Margot J, Tolin, David F, Tosetti, Michela, Tovar-Moll, Fernanda, Tsuchiyagaito, Aki, van Erp, Theo G M, van Wingen, Guido A, Vance, Alasdair, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Wallace, Gregory L, Wang, Zhen, Wolfers, Thoma, Yoncheva, Yuliya N, Yun, Je-Yeon, Zanetti, Marcus V, Zhou, Fengfeng, Ziegler, Georg C, Zierhut, Kathrin C, Zwiers, Marcel P, Thompson, Paul M, Stein, Dan J, Buitelaar, Jan, Franke, Barbara, van den Heuvel, Odile A, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, and APH - Mental Health
Subjects: Male, Research Report, Obsessive-Compulsive Disorder, Frontal cortex, Systems Analysis, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Hippocampal formation, Audiology, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Child, Obsessive-compulsive disorder (OCD), ComputingMilieux_MISCELLANEOUS, Intelligence quotient, Psychopathology, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, ABNORMALITIES, ENIGMA, Organ Size, 3. Good health, Psychiatry and Mental health, Autism spectrum disorder, Brain size, Cohort, Female, MRI, Adult, medicine.medical_specialty, CORTEX, Adolescent, DEFICIT HYPERACTIVITY DISORDER, Human Development, Neuroimaging, behavioral disciplines and activities, Article, 03 medical and health sciences, FIELD-STRENGTH, mental disorders, medicine, MEGA-ANALYSIS, Attention deficit hyperactivity disorder, Humans, Cortical surface, Structural MRI, Attention Deficit Disorder with Hyperactivity, Cerebrum, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, medicine.disease, 030227 psychiatry, VOXEL, Autism, business, 030217 neurology & neurosurgery
Abstract: ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.
Published: 2020

12. Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

Author: Francis M. Mondimore, Farah Klohn-Sagatholislam, Jana Strohmaier, Jens Wiltfang, Jay Raymond DePaulo, Udo Dannlowski, Markus Jäger, Moritz E. Wigand, Ion Anghelescu, Michael Bauer, Louise Frisén, Ashley L. Comes, Carsten Spitzer, Claire Slaney, Janice M. Fullerton, Giovanni Severino, Janusz K. Rybakowski, Andreas J. Fallgatter, Maria Hake, Martin Alda, Peter R. Schofield, Susanne Bengesser, Nirmala Akula, Stefan Herms, Paul D. Shilling, Franziska Degenhardt, Mazda Adli, Armin Birner, Alexandre Dayer, Cristiana Cruceanu, Fanny Senner, Peter Falkai, Maria Del Zompo, Mark A. Frye, Christian Simhandl, Stéphane Jamain, Andrea Pfennig, Layla Kassem, Sébastien Gard, Heike Anderson-Schmidt, Marion Leboyer, Peter P. Zandi, Susan L. McElroy, Martin Schalling, Sebastian Stierl, Detlef E. Dietrich, Frank Bellivier, Palmiero Monteleone, Sybille Schulz, Caterina Chillotti, Volker Arolt, Michael McCarthy, Alfonso Tortorella, Andreas Thiel, Marcella Rietschel, Kristina Adorjan, Tatyana Shekhtman, Maria Grigoroiu-Serbanescu, Jean-Michel Aubry, Daniela Reich-Erkelenz, Laura Flatau, Markus Reitt, Harald Scherk, Here Folkerts, Julia Veeh, Joanna Hauser, Fernando S. Goes, Philip B. Mitchell, Gustavo Turecki, John R. Kelsoe, Thomas Stamm, Sophia Stegmaier, Georg Juckel, Markus M. Nöthen, Lina Martinsson, Bárbara Arias, Vanessa Nieratschker, Clara Brichant-Petitjean, Antonio Benabarre, Bernhard T. Baune, James B. Potash, Urs Heilbronner, Caroline M. Nievergelt, Raffaella Ardau, Mikael Landén, Pablo Cervantes, Pavla Stopkova, Adam Wright, Tomas Novak, Scott R. Clark, Manfred Koller, Gonzalo Laje, Katrin Gade, Andreas J. Forstner, Sarah Kittel-Schneider, Susan G. Leckband, Sebastian Kliwicki, Guy A. Rouleau, Kim Bartholdi, Martin von Hagen, Per Hoffmann, Eva C. Schulte, Alessio Squassina, Monika Budde, Thomas G. Schulze, Eduard Vieta, Liping Hou, Jörg Zimmermann, Barbara König, Stephan Ripke, Sarah K. Tighe, Jean-Pierre Kahn, Julie Garnham, Piotr M. Czerski, Janos Kalman, Anna Gryaznova, Francis J. McMahon, Mario Maj, Thomas Becker, Thomas Ethofer, Andreas Reif, Carsten Konrad, Mirko Manchia, Lena Backlund, Jens Reimer, Urban Ösby, Esther Jiménez, Abesh Kumar Bhattacharjee, Marina Mitjans, Sergi Papiol, Stephanie H. Witt, Sven Cichon, Bruno Etain, Till F. M. Andlauer, Joanna M. Biernacka, Max Schmauß, Christian Figge, Fabian U. Lang, N. Lackner, Eva Z. Reininghaus, Francesc Colom, Catharina Lavebratt, K Oliver Schubert, Kalman, Janos L, Papiol, Sergi, Forstner, Andreas J, Heilbronner, Ur, Degenhardt, Franziska, Strohmaier, Jana, Adli, Mazda, Adorjan, Kristina, Akula, Nirmala, Alda, Martin, Anderson-Schmidt, Heike, Andlauer, Till Fm, Anghelescu, Ion-George, Ardau, Raffaella, Arias, Bárbara, Arolt, Volker, Aubry, Jean-Michel, Backlund, Lena, Bartholdi, Kim, Bauer, Michael, Baune, Bernhard T, Becker, Thoma, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Budde, Monika, Cervantes, Pablo, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Comes, Ashley L, Cruceanu, Cristiana, Czerski, Piotr M, Dannlowski, Udo, Dayer, Alexandre, Del Zompo, Maria, Depaulo, Jay Raymond, Dietrich, Detlef E, Étain, Bruno, Ethofer, Thoma, Falkai, Peter, Fallgatter, Andrea, Figge, Christian, Flatau, Laura, Folkerts, Here, Frisen, Louise, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grigoroiu-Serbanescu, Maria, Gryaznova, Anna, Hake, Maria, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hou, Liping, Jäger, Marku, Jamain, Stephane, Jiménez, Esther, Juckel, Georg, Kahn, Jean-Pierre, Kassem, Layla, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, Klohn-Sagatholislam, Farah, Koller, Manfred, König, Barbara, Konrad, Carsten, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lang, Fabian U, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J, Mcelroy, Susan L, Mcmahon, Francis J, Mitchell, Philip B, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nieratschker, Vanessa, Nievergelt, Caroline M, Novák, Toma, Ösby, Urban, Pfennig, Andrea, Potash, James B, Reich-Erkelenz, Daniela, Reif, Andrea, Reimer, Jen, Reininghaus, Eva, Reitt, Marku, Ripke, Stephan, Rouleau, Guy A, Rybakowski, Janusz K, Schalling, Martin, Scherk, Harald, Schmauß, Max, Schofield, Peter R, Schubert, K Oliver, Schulte, Eva C, Schulz, Sybille, Senner, Fanny, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Simhandl, Christian, Slaney, Claire M, Spitzer, Carsten, Squassina, Alessio, Stamm, Thoma, Stegmaier, Sophia, Stierl, Sebastian, Stopkova, Pavla, Thiel, Andrea, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Veeh, Julia, von Hagen, Martin, Wigand, Moritz E, Wiltfang, Jen, Witt, Stephanie, Wright, Adam, Zandi, Peter P, Zimmermann, Jörg, Nöthen, Marku, Rietschel, Marcella, and Schulze, Thomas G
Subjects: Adult, Male, Oncology, Multifactorial Inheritance, medicine.medical_specialty, Schizophrenia/genetics, Disease onset, Adolescent, early onset, Late onset, ddc:616.89, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Bipolar disorder, Child, Research Articles, Biological Psychiatry, bipolar disorder, Trastorn bipolar, business.industry, Bipolar Disorder/genetics, age at onset, polygenic risk score, schizophrenia, Age Factors, Bipolar Disorder, Female, Middle Aged, Phenotype, Schizophrenia, Original Articles, medicine.disease, Genetic architecture, 030227 psychiatry, Psychiatry and Mental health, Institutional repository, Clinical research, Esquizofrènia, Original Article, business, 030217 neurology & neurosurgery
Abstract: OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype. peerReviewed
Published: 2018

13. Analysis of shared heritability in common disorders of the brain

Author: Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nichola, Olesen, Je, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Denni, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thoma, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicita, Stroink, Han, Zimprich, Fritz, Gasser, Thoma, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thoma, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andrea, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragisko, Tziouvas, Konstantino, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thoma, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lar, Padyukov, Leonid, Halmi, Katherine A., Mitchell, Jame, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesú, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobia, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Aria, Doyle, Alysa E., Reif, Andrea, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikola, Bau, Claiton H.D., Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K., McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thoma, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Dougla, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B., Reinbold, Céline S., Fullerton, Janice M., Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Mühleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johanne, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Nicol Ferrier, I., Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlo, Anjorin, Adebayo, Stahl, Eli, Leber, Marku, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F.M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthia, Schoevers, Robert A., Beekman, Aartjan TF, Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Joseph Bienvenu, O., Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thoma, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andrea, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marco, Malaty, Irene A., Maras, Athanasio, McGrath, Lauren, Miguel, Eurípedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosário, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Foti, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, Jame, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Jani, Kučinskas, Vaiduti, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, Van Os, Jim, Pantelis, Christo, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Pano, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, Jame, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Fran, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alke, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chri, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M., Epidemiology, Radiology & Nuclear Medicine, Anttila, V, Bulik-Sullivan, B, Finucane, H, Walters, R, Bras, J, Duncan, L, Escott-Price, V, Falcone, G, Gormley, P, Malik, R, Patsopoulos, N, Ripke, S, Wei, Z, Yu, D, Lee, P, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J, Duron, E, Vardarajan, B, Reitz, C, Goate, A, Huentelman, M, Ilyas Kamboh, M, Larson, E, Rogaeva, E, George-Hyslop, P, Hakonarson, H, Kukull, W, Farrer, L, Barnes, L, Beach, T, Yesim Demirci, F, Head, E, Hulette, C, Jicha, G, Kauwe, J, Kaye, J, Leverenz, J, Levey, A, Lieberman, A, Pankratz, V, Poon, W, Quinn, J, Saykin, A, Schneider, L, Smith, A, Sonnen, J, Stern, R, Van Deerlin, V, Van Eldik, L, Harold, D, Russo, G, Rubinsztein, D, Bayer, A, Tsolaki, M, Proitsi, P, Fox, N, Hampel, H, Owen, M, Mead, S, Passmore, P, Morgan, K, Nöthen, M, Rossor, M, Lupton, M, Hoffmann, P, Kornhuber, J, Lawlor, B, Mcquillin, A, Al-Chalabi, A, Bis, J, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van Der Lee, S, De 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J, Tortorella, A, Maj, M, Gonidakis, F, Tziouvas, K, Papezova, H, Yilmaz, Z, Wagner, G, Cohen-Woods, S, Herms, S, Julia, A, Rabionet, R, Dick, D, Ripatti, S, Andreassen, O, Espeseth, T, Lundervold, A, Steen, V, Pinto, D, Scherer, S, Aschauer, H, Schosser, A, Alfredsson, L, Padyukov, L, Halmi, K, Mitchell, J, Strober, M, Bergen, A, Kaye, W, Szatkiewicz, J, Cormand, B, Ramos-Quiroga, J, Sánchez-Mora, C, Ribasés, M, Casas, M, Hervas, A, Arranz, M, Haavik, J, Zayats, T, Johansson, S, Williams, N, Dempfle, A, Rothenberger, A, Kuntsi, J, Oades, R, Banaschewski, T, Franke, B, Buitelaar, J, Vasquez, A, Doyle, A, Reif, A, Lesch, K, Freitag, C, Rivero, O, Palmason, H, Romanos, M, Langley, K, Rietschel, M, Witt, S, Dalsgaard, S, Børglum, A, Waldman, I, Wilmot, B, Molly, N, Bau, C, Crosbie, J, Schachar, R, Loo, S, Mcgough, J, Grevet, E, Medland, S, Robinson, E, Weiss, L, Bacchelli, E, Bailey, A, Bal, V, Battaglia, A, Betancur, C, Bolton, P, Cantor, R, Celestino-Soper, P, Dawson, G, De Rubeis, S, 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Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository
Subjects: Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.
Published: 2018

14. Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder

Author: Céline S. Reinbold, Andreas J. Forstner, Julian Hecker, Janice M. Fullerton, Per Hoffmann, Liping Hou, Urs Heilbronner, Franziska Degenhardt, Mazda Adli, Kazufumi Akiyama, Nirmala Akula, Raffaella Ardau, Bárbara Arias, Lena Backlund, Antonio Benabarre, Susanne Bengesser, Abesh K. Bhattacharjee, Joanna M. Biernacka, Armin Birner, Cynthia Marie-Claire, Pablo Cervantes, Guo-Bo Chen, Hsi-Chung Chen, Caterina Chillotti, Scott R. Clark, Francesc Colom, David A. Cousins, Cristiana Cruceanu, Piotr M. Czerski, Alexandre Dayer, Bruno Étain, Peter Falkai, Louise Frisén, Sébastien Gard, Julie S. Garnham, Fernando S. Goes, Paul Grof, Oliver Gruber, Ryota Hashimoto, Joanna Hauser, Stefan Herms, Stéphane Jamain, Esther Jiménez, Jean-Pierre Kahn, Layla Kassem, Sarah Kittel-Schneider, Sebastian Kliwicki, Barbara König, Ichiro Kusumi, Nina Lackner, Gonzalo Laje, Mikael Landén, Catharina Lavebratt, Marion Leboyer, Susan G. Leckband, Carlos A. López Jaramillo, Glenda MacQueen, Mirko Manchia, Lina Martinsson, Manuel Mattheisen, Michael J. McCarthy, Susan L. McElroy, Marina Mitjans, Francis M. Mondimore, Palmiero Monteleone, Caroline M. Nievergelt, Urban Ösby, Norio Ozaki, Roy H. Perlis, Andrea Pfennig, Daniela Reich-Erkelenz, Guy A. Rouleau, Peter R. Schofield, K. Oliver Schubert, Barbara W. Schweizer, Florian Seemüller, Giovanni Severino, Tatyana Shekhtman, Paul D. Shilling, Kazutaka Shimoda, Christian Simhandl, Claire M. Slaney, Jordan W. Smoller, Alessio Squassina, Thomas J. Stamm, Pavla Stopkova, Sarah K. Tighe, Alfonso Tortorella, Gustavo Turecki, Julia Volkert, Stephanie H. Witt, Adam J. Wright, L. Trevor Young, Peter P. Zandi, James B. Potash, J. Raymond DePaulo, Michael Bauer, Eva Reininghaus, Tomáš Novák, Jean-Michel Aubry, Mario Maj, Bernhard T. Baune, Philip B. Mitchell, Eduard Vieta, Mark A. Frye, Janusz K. Rybakowski, Po-Hsiu Kuo, Tadafumi Kato, Maria Grigoroiu-Serbanescu, Andreas Reif, Maria Del Zompo, Frank Bellivier, Martin Schalling, Naomi R. Wray, John R. Kelsoe, Martin Alda, Francis J. McMahon, Thomas G. Schulze, Marcella Rietschel, Markus M. Nöthen, Sven Cichon, University Hospital Basel [Basel], Universitätsklinikum Bonn (UKB), Neuroscience Research Australia (NeuRA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Department of Psychiatry and Psychotherapy, Georg-August-University [Göttingen], Department of Genomics, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Unit of Clinical Pharmacology, University-Hospital of Cagliari, Department of Psychiatry, Trinity College Dublin-St. James's Hospital, Mayo Clinic, University of Adelaide, McGill University = Université McGill [Montréal, Canada], Psychiatric Genetic Unit, Poznan University of Medical Sciences, Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Homburg, Department of Molecular Medicine, Karolinska Institutet [Stockholm], Service de psychiatrie adulte, Université Bordeaux Segalen - Bordeaux 2-Hôpital Charles Perrens, Dalhousie University [Halifax], Johns Hopkins University (JHU), Mood Disorders Center of Ottawa (MDCO), University of Ottawa [Ottawa], Department of Psychiatry [Heidelberg], University of Heidelberg, Medical Faculty, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), IrsiCaixa (Institut de Recerca de la Sida), Service de Psychiatrie et Psychologie Clinique, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Hôpital Jeanne-d'Arc, Mental Health Sciences Unit, University College of London [London] (UCL), Department of Adult Psychiatry, Abteilung Informatik und angewandte Kognitionswissenschaft [Duisburg] (INKO), Universität Duisburg-Essen [Essen], Hokkaido University Graduate School of Medicine, Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Molecular Medicine and Surgery department, University of California [San Diego] (UC San Diego), University of California-University of California, University of Antioquia, Università degli Studi di Salerno (UNISA), Department of Clinical Neuroscience, R&D Unit, Department of Psychiatry, Danderyd University Hospital–Karolinska Institutet, Fujita Health University School of Medicine, Center for Human Genetic Research, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Prince of Wales Medical Research Institute, University of New South Wales [Sydney] (UNSW), Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Massachusetts General Hospital [Boston], Prague Psychiatric Center, University of Prague, Università degli Studi di Perugia (UNIPG), Department of Psychiatry [Montréal], School of Psychiatry, Black Dog Institute-University of New South Wales [Sydney] (UNSW), Department of Mental Health, Johns Hopkins University and Hospital, Center for Sepsis Control & Care, Jena University Hospital, Medical University Graz, Department of Mental Health and Psychiatry, University Hospital of Geneva, Università degli studi della Campania 'Luigi Vanvitelli', Institute of Neuroscience, Hospital Clinic-IDIBAPS - CIBERSAM - ENBREC-University of Barcelona, Institute of Epidemiology and Preventive Medicine, National Taiwan University [Taiwan] (NTU), Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science [Wako] (RIKEN CBS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Psychiatric Hospital, Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, King‘s College London, Univerity of Mannheim, Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, McGill University, Optimisation Thérapeutique en Neuropsychopharmacologie (VariaPsy - U1144), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Ottawa [Ottawa] (uOttawa), Technische Universität Dresden (TUD), University of New South Wales [Sydney] (UNSW)-Black Dog Institute, RIKEN Brain Science Institute, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Friedrich Alexander University [Erlangen-Nürnberg], Universitat de Barcelona, Georg-August-University = Georg-August-Universität Göttingen, University of California (UC)-University of California (UC), Università degli Studi di Salerno = University of Salerno (UNISA), Danderyds sjukhus = Danderyd University Hospital, Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, Reinbold, Céline S., Forstner, Andreas J., Hecker, Julian, Fullerton, Janice M., Hoffmann, Per, Hou, Liping, Heilbronner, Ur, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Benabarre, Antonio, Bengesser, Susanne, Bhattacharjee, Abesh K., Biernacka, Joanna M., Birner, Armin, Marie-Claire, Cynthia, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Clark, Scott R., Colom, Francesc, Cousins, David A., Cruceanu, Cristiana, Czerski, Piotr M., Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Frisén, Louise, Gard, Sébastien, Garnham, Julie S., Goes, Fernando S., Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Jamain, Stéphane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Jaramillo, Carlos A. López, Macqueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, Mccarthy, Michael J., Mcelroy, Susan L., Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Ösby, Urban, Ozaki, Norio, Perlis, Roy H., Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A., Schofield, Peter R., Schubert, K. Oliver, Schweizer, Barbara W., Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M., Smoller, Jordan W., Squassina, Alessio, Stamm, Thomas J., Stopkova, Pavla, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie H., Wright, Adam J., Trevor Young, L., Zandi, Peter P., Potash, James B., Depaulo, J. Raymond, Bauer, Michael, Reininghaus, Eva, Novák, Tomáš, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T., Mitchell, Philip B., Vieta, Eduard, Frye, Mark A., Rybakowski, Janusz K., Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andrea, Zompo, Maria Del, Bellivier, Frank, Schalling, Martin, Wray, Naomi R., Kelsoe, John R., Alda, Martin, Mcmahon, Francis J., Schulze, Thomas G., Rietschel, Marcella, Nöthen, Markus M., and Cichon, Sven
Subjects: 0301 basic medicine, Genome-wide association study, Lithium (medication), lcsh:RC435-571, Bipolar disorder, Common variants, Lithium response, MicroRNA, Psychiatry and Mental Health, Common variant, Lithium, Biology, ddc:616.89, 03 medical and health sciences, lcsh:Psychiatry, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], common variants, medicine, Manic-depressive illness, ddc:610, Gene, ComputingMilieux_MISCELLANEOUS, Trastorno Bipolar, Original Research, Psychiatry, bipolar disorder, Genetics, MicroARNs, Trastorn bipolar, genome-wide association study, microRNA, medicine.disease, genome-wide association stud, Liti, Phenotype, 3. Good health, MicroRNAs, Psychiatry and Mental health, 030104 developmental biology, Schizophrenia, Multiple comparisons problem, Litio, medicine.symptom, Mania, lithium response, medicine.drug
Abstract: Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGenGWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genomewide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted. COL0029147
Published: 2018

15. Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study

Author: Claire O'Donovan, Gustavo Turecki, Frank Bellivier, Palmiero Monteleone, Tatyana Shekhtman, Bárbara Arias, Paul Grof, Sébastien Gard, Tomas Novak, Maria Del Zompo, Martin Schalling, Sarah Kittel-Schneider, Hsi-Chung Chen, Eduard Vieta, Claire Slaney, Katzutaka Shimoda, J. Raymond DePaulo, Martin Alda, Liping Hou, Kazufumi Akiyama, Louise Frisén, Gonzalo Laje, Maria Grigoroiu-Serbanescu, Mikael Landén, Nirmala Akula, Cristiana Cruceanu, Tadafumi Kato, Marion Leboyer, Lina Martinsson, Alessio Squassina, Andrea Hofmann, James B. Potash, Barbara König, Markus M. Nöthen, Giovanni Severino, Michael McCarthy, Philip B. Mitchell, Mario Maj, Ichiro Kusumi, Caroline M. Nievergelt, Jean-Pierre Kahn, Ryota Hashimoto, Joanna M. Biernacka, Sebastian Kliwicki, Francis J. McMahon, Guy A. Rouleau, Thomas Stamm, Pablo Cervantes, Alexandre Dayer, Julia Volkert, Po-Hsiu Kuo, Urs Heilbronner, Per Hoffmann, Janice M. Fullerton, Raffaella Ardau, Julie Garnham, Scott R. Clark, Layla Kassem, Fasil Tekola-Ayele, Peter R. Schofield, Nina Dalkner, Caterina Chillotti, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Alfonso Tortorella, Adam Wright, Joanna Hauser, Peter P. Zandi, Piotr M. Czerski, Eva Z. Reininghaus, Fernando S. Goes, Jean-Michel Aubry, Antonio Benabarre, Bernhard T. Baune, Thomas G. Schulze, Francesc Colom, Marcella Rietschel, Andrea Pfennig, Catharina Lavebratt, Andreas J. Forstner, Paul D. Shilling, Mazda Adli, Armin Birner, Andreas Reif, Mirko Manchia, Susan G. Leckband, Azmeraw T. Amare, Susan L. McElroy, Michael Bauer, Norio Ozaki, Urban Ösby, Janusz K. Rybakowski, Pavla Stopkova, Esther Jiménez, Christian Simhandl, Abesh Kumar Bhattacharjee, Yi-Hsiang Hsu, John R. Kelsoe, Marina Mitjans, Sergi Papiol, Clara Brichant-Petitjean, Mark A. Frye, Stephanie H. Witt, Franziska Degenhardt, Sven Cichon, Bruno Etain, Lena Backlund, Peter Falkai, Barbara W. Schweizer, Stéphane Jamain, Amare, Azmeraw T., Schubert, Klaus Oliver, Hou, Liping, Clark, Scott R., Papiol, Sergi, Heilbronner, Ur, Degenhardt, Franziska, Tekola-Ayele, Fasil, Hsu, Yi-Hsiang, Shekhtman, Tatyana, Adli, Mazda, Akula, Nirmala, Akiyama, Kazufumi, Ardau, Raffaella, Arias, Bã¡rbara, Aubry, Jean-Michel, Backlund, Lena, Bhattacharjee, Abesh Kumar, Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Biernacka, Joanna M., Birner, Armin, Brichant-Petitjean, Clara, Cervantes, Pablo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Cruceanu, Cristiana, Czerski, Piotr M., Dalkner, Nina, Dayer, Alexandre, Del Zompo, Maria, Depaulo, J. Raymond, Ã tain, Bruno, Falkai, Peter, Forstner, Andreas J., Frisen, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sã©bastien, Garnham, Julie S., Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jimã©nez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kuo, Po-Hsiu, Kato, Tadafumi, Kelsoe, John, Kittel-Schneider, Sarah, Kliwicki, Sebastian, Kã¶nig, Barbara, Kusumi, Ichiro, Laje, Gonzalo, Landã©n, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G., Tortorella, Alfonso, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J., Mcelroy, Susan, Colom, Francesc, Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Nievergelt, Caroline M., Nã¶then, Markus M., Novã¡k, Toma, O'Donovan, Claire, Ozaki, Norio, Ã sby, Urban, Pfennig, Andrea, Potash, James B., Reif, Andrea, Reininghaus, Eva, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Schofield, Peter R., Schweizer, Barbara W., Severino, Giovanni, Shilling, Paul D., Shimoda, Katzutaka, Simhandl, Christian, Slaney, Claire M., Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Maj, Mario, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie, Wright, Adam, Zandi, Peter P., Mitchell, Philip B., Bauer, Michael, Alda, Martin, Rietschel, Marcella, Mcmahon, Francis J., Schulze, Thomas G., and Baune, Bernhard T.
Subjects: Male, Oncology, Multifactorial Inheritance, Bipolar Disorder, Lithium (medication), Genome-wide association study, THERAPY, chemistry.chemical_compound, ddc:616.89, 0302 clinical medicine, HLA Antigens, Spectrum disorder, Original Investigation, RISK, Mood stabilizer, Middle Aged, GLYCOGEN-SYNTHASE KINASE-3, 3. Good health, PREVALENCE, Treatment Outcome, Schizophrenia, Psychiatry and Mental Health, Female, Schizophrenic Psychology, Genetic Load, GLYCOGEN-SYNTHASE KINASE-3, CYTOKINE PRODUCTION, PROPHYLACTIC LITHIUM, SPECTRUM DISORDER, RISK, PREVALENCE, METAANALYSIS, GENETICS, THERAPY, PROFILE, medicine.drug, Adult, medicine.medical_specialty, Genotype, GENETICS, medicine.drug_class, PROFILE, PROPHYLACTIC LITHIUM, 03 medical and health sciences, Lithium Carbonate, Internal medicine, mental disorders, medicine, Humans, Bipolar disorder, Psychiatry, METAANALYSIS, SPECTRUM DISORDER, Inflammation, business.industry, Lithium carbonate, Odds ratio, CYTOKINE PRODUCTION, medicine.disease, 030227 psychiatry, chemistry, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: IMPORTANCE Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ). OBJECTIVES To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association. DESIGN, SETTING, AND PARTICIPANTS A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013.Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36 989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017. MAIN OUTCOMES AND MEASURES Treatment response to lithiumwas defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained. RESULTS Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P < 5 ? 10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95%CI, 1.42-8.41) at the first decile to 2.03 (95%CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines. CONCLUSIONS AND RELEVANCE This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
Published: 2018

16. Common and rare variants of microRNA genes in autism spectrum disorders

Author: Isabel Rueda, Nanda Rommelse, Luis A. Pérez-Jurado, Elena Bacchelli, Christine M. Freitag, Claudio Toma, Marta Salgado, Barbara Franke, Bru Cormand, Andreas Reif, Rafael Valdés-Mas, Xose S. Puente, Amaia Hervás, Luigi Mazzone, Bàrbara Torrico, Jan K. Buitelaar, Agatino Battaglia, Toma, Claudio, Torrico, Bàrbara, Hervás, Amaia, Salgado, Marta, Rueda, Isabel, Valdés-Mas, Rafael, Buitelaar, Jan K., Rommelse, Nanda, Franke, Barbara, Freitag, Christine, Reif, Andrea, Pérez-Jurado, Luis Alberto, Battaglia, Agatino, Mazzone, Luigi, Bacchelli, Elena, Puente, Xose S., and Cormand, Bru
Subjects: Genetics, MicroRNAs, autistic disorder, biological psychiatry, exome, genetic association studies, Candidate gene, MicroRNAs, autistic disorder, biological psychiatry, exome, genetic association studies, genetic association studie, MicroRNA, Single-nucleotide polymorphism, Genome-wide association study, Biology, medicine.disease, behavioral disciplines and activities, Settore MED/39 - Neuropsichiatria Infantile, Psychiatry and Mental health, Pooled analysis, mental disorders, microRNA, medicine, Autism, Exome, Gene, Biological Psychiatry
Abstract: Objectives. MicroRNAs (miRNAs) are post-transcriptional regulators that have been shown to be involved in disease susceptibility. Here we explore the possible contribution of common and rare variants in miRNA genes in autism spectrum disorders (ASD). Methods. A total of 350 tag SNPs from 163 miRNA genes were genotyped in 636 ASD cases and 673 controls. A replication study was performed in a sample of 449 ASD cases and 415 controls. Additionally, rare variants in 701 miRNA genes of 41 ASD patients were examined using whole-exome sequencing. Results. The most significant association in the discovery sample was obtained for the miR-133b/miR-206 cluster (rs16882131, P = 0.00037). The replication study did not reach significance. However, the pooled analysis (1,085 cases and 1,088 controls) showed association with two miRNA clusters: miR-133b/miR-206 (rs16882131, permP = 0.037) and miR-17/miR-18a/miR-19a/miR-20a/miR-19b-1/miR92a-1 (rs6492538, permP = 0.019). Both miR-133b and miR-206 regulate the MET gene, previously associated with ASD. Rare variant analysis identified mutations in several miRNA genes, among them miR-541, a brain-specific miRNA that regulates SYN1, found mutated in ASD. Conclusions. Although our results do not establish a clear role for miRNAs in ASD, we pinpointed a few candidate genes. Further exome and GWAS studies are warranted to get more insight into their potential contribution to the disorder.
Published: 2015

17. Genetic variants associated with response to lithium treatment in bipolar disorder:a genome-wide association study

Author: Ryota Hashimoto, Andrea Hofmann, Gustavo Turecki, N. Lackner, Philip B. Mitchell, Bárbara Arias, Urban Ösby, J. Raymond DePaulo, Martin Alda, Julie Garnham, Esther Jiménez, Abesh Kumar Bhattacharjee, Peter P. Zandi, Clara Brichant-Petitjean, Frank Bellivier, Marina Mitjans, Palmiero Monteleone, Eduard Vieta, Liping Hou, Eva Z. Reininghaus, Raffaella Ardau, Paul D. Shilling, Mazda Adli, Armin Birner, Marion Leboyer, Lena Backlund, Andreas J. Forstner, David A. Cousins, Francesc Colom, Catharina Lavebratt, K Oliver Schubert, Barbara W. Schweizer, Mario Maj, Kazufumi Akiyama, Antoni Benabarre, Julia Volkert, Alessio Squassina, Marcella Rietschel, Stephanie H. Witt, Gonzalo Laje, Louise Frisén, Jordan W. Smoller, Paul Grof, Tomas Novak, L. Trevor Young, Sven Cichon, Bruno Etain, Ichiro Kusumi, Sarah K. Tighe, Sarah Kittel-Schneider, Florian Seemüller, Jean-Pierre Kahn, Markus M. Nöthen, Tadafumi Kato, Alexandre Dayer, Caroline M. Nievergelt, Mirko Manchia, Francis J. McMahon, Peter R. Schofield, Susanne Bengesser, Po-Hsiu Kuo, Stefan Herms, Scott R. Clark, Piotr M. Czerski, Oliver Gruber, Franziska Degenhardt, Mark A. Frye, Joanna M. Biernacka, Christian Simhandl, Guo-Bo Chen, Adam Wright, Sébastien Gard, Peter Falkai, Carlos Jaramillo, Stéphane Jamain, Roy H. Perlis, Andrea Pfennig, Tatyana Shekhtman, Maria Del Zompo, Clarissa de Rosalmeida Dantas, Thomas G. Schulze, Alfonso Tortorella, Francis M. Mondimore, John R. Kelsoe, Jean-Michel Aubry, Mikael Landén, Andreas Reif, Naomi R. Wray, Martin Schalling, Janice M. Fullerton, Nirmala Akula, Claudio E. M. Banzato, Elise T. Bui, Per Hoffmann, Sebastian Kliwicki, Guy A. Rouleau, Maria Grigoroiu-Serbanescu, Glenda MacQueen, Lina Martinsson, Giovanni Severino, Norio Ozaki, Daniela Reich-Erkelenz, Layla Kassem, Manuel Mattheisen, Pavla Stopkova, Michael Bauer, Caterina Chillotti, Kazutaka Shimoda, Bernhard T. Baune, Janusz K. Rybakowski, Thomas Stamm, Joanna Hauser, Fernando S. Goes, Urs Heilbronner, James B. Potash, Susan L. McElroy, Barbara König, Susan G. Leckband, Michael McCarthy, Hsi-Chung Chen, Claire Slaney, Cristiana Cruceanu, Pablo Cervantes, Hou, Liping, Heilbronner, Ur, Degenhardt, Franziska, Adli, Mazda, Akiyama, Kazufumi, Akula, Nirmala, Ardau, Raffaella, Arias, Bárbara, Backlund, Lena, Banzato, Claudio E M, Benabarre, Antoni, Bengesser, Susanne, Bhattacharjee, Abesh Kumar, Biernacka, Joanna M, Birner, Armin, Brichant-Petitjean, Clara, Bui, Elise T, Cervantes, Pablo, Chen, Guo-Bo, Chen, Hsi-Chung, Chillotti, Caterina, Cichon, Sven, Clark, Scott R, Colom, Francesc, Cousins, David A, Cruceanu, Cristiana, Czerski, Piotr M, Dantas, Clarissa R, Dayer, Alexandre, Étain, Bruno, Falkai, Peter, Forstner, Andreas J, Frisén, Louise, Fullerton, Janice M, Gard, Sébastien, Garnham, Julie S, Goes, Fernando S, Grof, Paul, Gruber, Oliver, Hashimoto, Ryota, Hauser, Joanna, Herms, Stefan, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kittel-Schneider, Sarah, Kliwicki, Sebastian, König, Barbara, Kusumi, Ichiro, Lackner, Nina, Laje, Gonzalo, Landén, Mikael, Lavebratt, Catharina, Leboyer, Marion, Leckband, Susan G, Jaramillo, Carlos A López, Macqueen, Glenda, Manchia, Mirko, Martinsson, Lina, Mattheisen, Manuel, Mccarthy, Michael J, Mcelroy, Susan L, Mitjans, Marina, Mondimore, Francis M, Monteleone, Palmiero, Nievergelt, Caroline M, Nöthen, Markus M, Ösby, Urban, Ozaki, Norio, Perlis, Roy H, Pfennig, Andrea, Reich-Erkelenz, Daniela, Rouleau, Guy A, Schofield, Peter R, Schubert, K Oliver, Schweizer, Barbara W, Seemüller, Florian, Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D, Shimoda, Kazutaka, Simhandl, Christian, Slaney, Claire M, Smoller, Jordan W, Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Tighe, Sarah K, Tortorella, Alfonso, Turecki, Gustavo, Volkert, Julia, Witt, Stephanie, Wright, Adam, Young, L Trevor, Zandi, Peter P, Potash, James B, Depaulo, J Raymond, Bauer, Michael, Reininghaus, Eva Z, Novák, Toma, Aubry, Jean-Michel, Maj, Mario, Baune, Bernhard T, Mitchell, Philip B, Vieta, Eduard, Frye, Mark A, Rybakowski, Janusz K, Kuo, Po-Hsiu, Kato, Tadafumi, Grigoroiu-Serbanescu, Maria, Reif, Andrea, Del Zompo, Maria, Bellivier, Frank, Schalling, Martin, Wray, Naomi R, Kelsoe, John R, Alda, Martin, Rietschel, Marcella, Mcmahon, Francis J, and Schulze, Thomas G
Subjects: Male, Glial Cell Line-Derived Neurotrophic Factor Receptors, Bipolar Disorder, Genotype, Genome-wide association study, Single-nucleotide polymorphism, Bipolar Disorder/drug therapy/genetics, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic variation, Medicine, Humans, Bipolar disorder, Prospective Studies, Allele, Polymorphism, Lithium Compounds/therapeutic use, Genetics, business.industry, Medicine (all), Genetic Variation, General Medicine, Single Nucleotide, Middle Aged, medicine.disease, Polymorphism, Single Nucleotide/genetics, 030227 psychiatry, 3. Good health, Phenotype, Treatment Outcome, Female, Genome-Wide Association Study, Lithium Compounds, business, 030217 neurology & neurosurgery, Imputation (genetics), Pharmacogenetics, Glial Cell Line-Derived Neurotrophic Factor Receptors/genetics
Abstract: BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified.METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis.FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0).INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings.FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.
Published: 2016

18. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

Author: Philip B. Mitchell, Clara Brichant-Petitjean, Raffaella Ardau, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Sebastian Zöllner, Christina M. Hultman, Shashi Hitturlingappa, Maria Hipolito, Louise Frisén, Thomas W. Mühleisen, Layla Kassem, Christian Simhandl, Urban Ösby, Frank Bellivier, Peter Falkai, Alessio Squassina, Jana Strohmaier, Esther Jiménez, Palmiero Monteleone, Caterina Chillotti, Stéphane Jamain, Peter P. Zandi, Abesh Kumar Bhattacharjee, Tony Davis, Sarah K. Tighe, William Byerley, Jean-Pierre Kahn, Michael Bauer, Nicholas J. Schork, Joanna Hauser, Andreas J. Forstner, Francis J. McMahon, Peter Propping, Marina Mitjans, Tiffany A. Greenwood, Alfonso Tortorella, Fernando S. Goes, Szabolcs Szelinger, Tomas Novak, Erin N. Smith, Andrea Pfennig, Susan G. Leckband, Pablo Cervantes, Sarah Kittel-Schneider, Sébastien Gard, Adam Wright, Tatiana Foroud, Joanna M. Biernacka, Jean-Michel Aubry, Marcella Rietschel, Elliot S. Gershon, Janusz K. Rybakowski, John R. Kelsoe, Stephanie H. Witt, Elise T. Bui, Sarah E. Bergen, Tatyana Shekhtman, Thomas G. Schulze, Sven Cichon, Julia Volkert, Thomas Stamm, Eduard Vieta, Jie Song, Liping Hou, Markus M. Nöthen, Bruno Etain, Mikael Landén, Caroline M. Nievergelt, Mirko Manchia, William Coryell, Howard J. Edenberg, Andreas Reif, Urs Heilbronner, Gonzalo Laje, Lena Backlund, Wade H. Berrettini, Martin Schalling, Franziska Degenhardt, Susan L. McElroy, Mario Maj, Francis M. Mondimore, Peng Zhang, Stefanie Heilmann-Heimbach, Janice M. Fullerton, Daniel L. Koller, James B. Potash, Michael McCarthy, Barbara W. Schweizer, Rebecca McKinney, Nirmala Akula, Sebastian Kliwicki, Guy A. Rouleau, N. Lackner, William Lawson, Melvin G. McInnis, Eva Z. Reininghaus, Maria Grigoroiu-Serbanescu, Pavla Stopkova, Francesc Colom, Catharina Lavebratt, Judith A. Badner, Mark A. Frye, Alexandre Dayer, Giovanni Severino, Maren Lang, John P. Rice, Per Hoffmann, William A. Scheftner, Lina Martinsson, Pamela B. Mahon, Piotr M. Czerski, Paul D. Shilling, Mazda Adli, Armin Birner, David Craig, Gustavo Turecki, Bárbara Arias, Evaristus A. Nwulia, Thomas B. Barrett, Cinnamon S. Bloss, Marion Leboyer, Chunyu Liu, Maria Del Zompo, Antonio Benabarre, Bernhard T. Baune, Fabian Streit, John I. Nurnberger, Barbara König, Anna Maaser, Wolfgang Maier, Julie Garnham, Claire Slaney, Johannes Schumacher, Cristiana Cruceanu, J. Raymond DePaulo, Martin Alda, Andrea Hofmann, Hou, Liping, Bergen, Sarah E., Akula, Nirmala, Song, Jie, Hultman, Christina M., Landén, Mikael, Adli, Mazda, Alda, Martin, Ardau, Raffaella, Arias, Barbara, Aubry, Jean-Michel, Backlund, Lena, Badner, Judith A., Barrett, Thomas B., Bauer, Michael, Baune, Bernhard T., Bellivier, Frank, Benabarre, Antonio, Bengesser, Susanne, Berrettini, Wade H., Bhattacharjee, Abesh Kumar, Biernacka, Joanna M., Birner, Armin, Bloss, Cinnamon S., Brichant-Petitjean, Clara, Bui, Elise T., Byerley, William, Cervantes, Pablo, Chillotti, Caterina, Cichon, Sven, Colom, Francesc, Coryell, William, Craig, David W., Cruceanu, Cristiana, Czerski, Piotr M., Davis, Tony, Dayer, Alexandre, Degenhardt, Franziska, Del Zompo, Maria, Depaulo, J. Raymond, Edenberg, Howard J., Étain, Bruno, Falkai, Peter, Foroud, Tatiana, Forstner, Andreas J., Frisén, Louise, Frye, Mark A., Fullerton, Janice M., Gard, Sébastien, Garnham, Julie S., Gershon, Elliot S., Goes, Fernando S., Greenwood, Tiffany A., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Heilbronner, Ur, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hipolito, Maria, Hitturlingappa, Shashi, Hoffmann, Per, Hofmann, Andrea, Jamain, Stephane, Jiménez, Esther, Kahn, Jean-Pierre, Kassem, Layla, Kelsoe, John R., Kittel-Schneider, Sarah, Kliwicki, Sebastian, Koller, Daniel L., König, Barbara, Lackner, Nina, Laje, Gonzalo, Lang, Maren, Lavebratt, Catharina, Lawson, William B., Leboyer, Marion, Leckband, Susan G., Liu, Chunyu, Maaser, Anna, Mahon, Pamela B., Maier, Wolfgang, Maj, Mario, Manchia, Mirko, Martinsson, Lina, Mccarthy, Michael J., Mcelroy, Susan L., Mcinnis, Melvin G., Mckinney, Rebecca, Mitchell, Philip B., Mitjans, Marina, Mondimore, Francis M., Monteleone, Palmiero, Mühleisen, Thomas W., Nievergelt, Caroline M., Nöthen, Markus M., Novák, Toma, Nurnberger, John I., Nwulia, Evaristus A., Ösby, Urban, Pfennig, Andrea, Potash, James B., Propping, Peter, Reif, Andrea, Reininghaus, Eva, Rice, John, Rietschel, Marcella, Rouleau, Guy A., Rybakowski, Janusz K., Schalling, Martin, Scheftner, William A., Schofield, Peter R., Schork, Nicholas J., Schulze, Thomas G., Schumacher, Johanne, Schweizer, Barbaraw., Severino, Giovanni, Shekhtman, Tatyana, Shilling, Paul D., Simhandl, Christian, Slaney, Claire M., Smith, Erin N., Squassina, Alessio, Stamm, Thoma, Stopkova, Pavla, Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolc, Tighe, Sarah K., Tortorella, Alfonso, Turecki, Gustavo, Vieta, Eduard, Volkert, Julia, Witt, Stephanie H., Wright, Adam, Zandi, Peter P., Zhang, Peng, Zollner, Sebastian, and Mcmahon, Francis J.
Subjects: Male, 0301 basic medicine, Bipolar Disorder, Receptor, ErbB-2, Genome-wide association study, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, ddc:616.89, 0302 clinical medicine, Genetic, Molecular Biology, Genetics, Genetics (clinical), medicine, Humans, Bipolar disorder, Genetic association, Chromosomes, Human, X, Association Studies Articles, Case-control study, General Medicine, Odds ratio, Heritability, medicine.disease, 3. Good health, 030104 developmental biology, Meta-analysis, Female, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 × 10 (-) (9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 × 10 (-) (9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Published: 2016

19. Contribution of common and rare variants of the PTCHD1 gene to autism spectrum disorders and intellectual disability

Author: Jan K. Buitelaar, Luigi Mazzone, Nanda Rommelse, Agatino Battaglia, Janita Bralten, Noèlia Fernàndez-Castillo, Christine M. Freitag, Montserrat Milà, Isabel Rueda, Andreas Reif, Marta Salgado, Anoek M. Oerlemans, Bru Cormand, Claudio Toma, Bàrbara Torrico, Elena Maestrini, Amaia Hervás, Torrico, Bàrbara, Fernàndez-Castillo, Noèlia, Hervás, Amaia, Milà, Montserrat, Salgado, Marta, Rueda, Isabel, Buitelaar, Jan K., Rommelse, Nanda, Oerlemans, Anoek M., Bralten, Janita, Freitag, Christine M., Reif, Andrea, Battaglia, Agatino, Mazzone, Luigi, Maestrini, Elena, Cormand, Bru, and Toma, Claudio
Subjects: Male, Autism Spectrum Disorder, Case-Control Studies, Cell Line, Tumor, Female, Humans, Intellectual Disability, Membrane Proteins, Mutation, Missense, Promoter Regions, Genetic, Trinucleotide Repeats, Polymorphism, Single Nucleotide, Single-nucleotide polymorphism, Biology, Bioinformatics, Article, Cell Line, Promoter Regions, Genetic, Gene duplication, mental disorders, Genetics, medicine, Missense mutation, Copy-number variation, Allele, Polymorphism, Genetics (clinical), Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Tumor, Single Nucleotide, medicine.disease, Settore MED/39 - Neuropsichiatria Infantile, Autism spectrum disorder, Mutation, Autism, Missense, Trinucleotide repeat expansion
Abstract: Recent findings revealed rare copy number variants and missense changes in the X-linked gene PTCHD1 in autism spectrum disorder (ASD) and intellectual disability (ID). Here, we aim to explore the contribution of common PTCHD1 variants in ASD and gain additional evidence for the role of rare variants of this gene in ASD and ID. A two-stage case-control association study investigated 28 tag single nucleotide polymorphisms (SNPs) in 994 ASD cases and 1035 controls from four European populations. Mutation screening was performed in 673 individuals who included 240 ASD cases, 183 ID patients and 250 controls. The case-control association study showed a significant association with rs7052177 (P=6.13E-4) in the ASD discovery sample that was replicated in an independent sample (P=0.03). A Mantel-Haenszel meta-analysis for rs7052177T considering the four European populations showed an odds ratio of 0.58 (P=7E-05). This SNP is predicted to be located in a transcription factor binding site. No rare missense PTCHD1 variants were found in our ASD cohort and only one was identified in the ID sample. A duplication (27 bp) in the promoter region, absent from 590 controls, was found in three ASD patients (Fisher exact test, P=0.024). A gene reporter assay showed a significant decrease in the transcriptional activity (26%) driven by this variant. Moreover, we found that the longest allele of a trinucleotide repeat located upstream from PTCHD1 was associated with ASD (P=0.003, permP=0.0186). Our results further support the involvement of PTCHD1 in ASD, suggesting that both common and rare variants contribute to the disorder.
Published: 2015

20. Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats

Author: Klaus V. Toyka, Thomas Wultsch, Andreas Weishaupt, Daniela Perani, Michele Solimena, Christian Geis, Claudia Sommer, Manfred Heckmann, Ronald Dirkx, Andreas Reif, Franco Folli, Manfred Gerlach, Benedikt Grünewald, Geis, Christian, Weishaupt, Andrea, Gruenewald, Benedikt, Wultsch, Thoma, Reif, Andrea, Gerlach, Manfred, Dirkx, Ron, Solimena, Michele, Perani, DANIELA FELICITA L., Heckmann, Manfred, Nullv, nullToyka Klau, Folli, Franco, and Sommer, Claudia
Subjects: Flumazenil, Central Nervous System, Anatomy and Physiology, Glutamate decarboxylase, Medizin, lcsh:Medicine, Anxiety, Hippocampus, Behavioral Neuroscience, Immune Physiology, Neurobiology of Disease and Regeneration, Carbon Radioisotopes, Young adult, lcsh:Science, Immune Response, Cells, Cultured, gamma-Aminobutyric Acid, Neurons, Psychiatry, Multidisciplinary, Behavior, Animal, Glutamate Decarboxylase, Animal Models, Neurotransmitters, Middle Aged, Amygdala, Anxiety Disorders, medicine.anatomical_structure, Mental Health, Neurology, Medicine, Female, medicine.symptom, Stiff person syndrome, Research Article, Adult, medicine.medical_specialty, Immune Cells, Immunology, Neurophysiology, Immunoglobulins, Stiff-Person Syndrome, Immunopathology, Biology, behavioral disciplines and activities, Antibodies, Autoimmune Diseases, Young Adult, Model Organisms, mental disorders, medicine, Animals, Humans, ddc:610, Antibody-Producing Cells, Panic disorder, lcsh:R, Autoantibody, Immunity, medicine.disease, Rats, Immunoglobulin G, Positron-Emission Tomography, Immune System, Synapses, Humoral Immunity, Rat, Clinical Immunology, lcsh:Q, Molecular Neuroscience, Agoraphobia, Neuroscience
Abstract: Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11) C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
Published: 2011

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20 results on '"Reif, Andrea"'

1. Männlichkeiten

2. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups. III. Naphthocoronene Series, Ovalene Series, and First Members of Some Higher Series

3. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups. II. Pyrene Series, Naphthopyrene Series, and Coronene Series.

4. Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups I. Benzene Series.

5. Erratum: Standard Chemical Thermodynamic Properties of Polycyclic Aromatic Hydrocarbons and Their Isomer Groups I. Benzene Series [J. Phys. Chem. Ref. Data 17, 241 (1988)].

6. The relationship between physical and mental health: an update from the WPA Working Group on Managing Comorbidity of Mental and Physical Health

7. Association between polarity of first episode and solar insolation in bipolar I disorder

8. Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends: An interrupted time series analysis in 33 countries

9. Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: Machine learning approach

10. Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

11. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders:Findings from the ENIGMA ADHD, ASD, and OCD working groups

12. Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study

13. Analysis of shared heritability in common disorders of the brain

14. Analysis of the Influence of microRNAs in Lithium Response in Bipolar Disorder

15. Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: A genome-wide association study

16. Common and rare variants of microRNA genes in autism spectrum disorders

17. Genetic variants associated with response to lithium treatment in bipolar disorder:a genome-wide association study

18. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder

19. Contribution of common and rare variants of the PTCHD1 gene to autism spectrum disorders and intellectual disability

20. Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats

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