المؤلفون: Schijven, Dick, Postema, Merel C, Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja MC, van Haren, Neeltje EM, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T, Agartz, Ingrid, Andreassen, Ole A, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E, Schall, Ulrich, Scott, Rodney J, Carr, Vaughan J, Green, Melissa J, Henskens, Frans A, Loughland, Carmel M, Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo TJ, Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D, Bustillo, Juan, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D, Ford, Judith M, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N, Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, Antonucci, Linda A

المصدر: Proceedings of the National Academy of Sciences of the United States of America. 120(14)

مصطلحات موضوعية: Brain, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Case-Control Studies, Schizophrenia, Female, Male, Functional Laterality, asymmetry, brain imaging, cortical, subcortical, Clinical Research, Mental Health, Neurosciences, Brain Disorders, Mental health

الوصف: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/11b116n6Test

المؤلفون: Liu, Dongjing, Meyer, Dara, Fennessy, Brian, Feng, Claudia, Cheng, Esther, Johnson, Jessica, Park, You Jeong, Rieder, Marysia-Kolbe, Ascolillo, Steven, de Pins, Agathe, Dobbyn, Amanda, Lebovitch, Dannielle, Moya, Emily, Nguyen, Tan-Hoang, Wilkins, Lillian, Hassan, Arsalan, Aghanwa, Henry, Burdick, Katherine E., Buxbaum, Joseph D., Domenici, Enrico, Frangou, Sophia, Hartmann, Annette M., Laurent-Levinson, Claudine, Malhotra, Dheeraj, Pato, Carlos N., Pato, Michele T., Ressler, Kerry, Roussos, Panos, Rujescu, Dan, Arango, Celso, Bertolino, Alessandro, Blasi, Giuseppe, Bocchio-Chiavetto, Luisella, Campion, Dominique, Carr, Vaughan, Fullerton, Janice M., Gennarelli, Massimo, Gonzalez-Penas, Javier, Levinson, Douglas F., Mowry, Bryan, Nimgaokar, Vishwajit L., Pergola, Giulio, Rampino, Antonio, Cervilla, Jorge A., Rivera, Margarita, Schwab, Sibylle G., Wildenauer, Dieter B., Daly, Mark, Neale, Benjamin, Singh, Tarjinder, O'Donovan, Michael C., Owen, Michael J., Walters, James T., Ayub, Muhammad, Malhotra, Anil K., Lencz, Todd, Sullivan, Patrick F., Sklar, Pamela, Stahl, Eli A., Huckins, Laura M., Charney, Alexander W., Aghanwa, Henry S., Ansari, Moin, Asif, Aftab, Aslam, Rubina, Ayuso, Jose L., Bigdeli, Tim, Bignotti, Stefano, Bobes, Julio, Bradley, Bekh, Buckley, Peter, Cairns, Murray J., Catts, Stanley V., Chaudhry, Abdul Rashid, Cohen, David, Collins, Brett L., Consoli, Angele, Costas, Javier, Crespo-Facorro, Benedicto, Daskalakis, Nikolaos P., Davidson, Michael, Davis, Kenneth L., Dickerson, Faith, Dogar, Imtiaz A., Drapeau, Elodie, Fananas, Lourdes, Fanous, Ayman, Fatima, Warda, Fatjo, Mar, Filippich, Cheryl, Friedman, Joseph, Fullard, John F., Georgakopoulos, Penelope, Giannitelli, Marianna, Giegling, Ina, Green, Melissa J., Guillin, Olivier, Gutierrez, Blanca, Handoko, Herlina Y., Hansen, Stella Kim, Haroon, Maryam, Haroutunian, Vahram, Henskens, Frans A., Hussain, Fahad, Jablensky, Assen V., Junejo, Jamil, Kelly, Brian J., Khan, Shams-Ud-Din A., Khan, Muhammad N. S., Khan, Anisuzzaman, Khawaja, Hamid R., Khizar, Bakht, Kleopoulos, Steven P., Knowles, James, Konte, Bettina, Kusumawardhani, Agung A. A. A., Leghari, Naeemullah, Liu, Xudong, Lori, Adriana, Loughland, Carmel M., Mahmood, Khalid, Mahmood, Saqib, Malaspina, Dolores, Malik, Danish, McNaughton, Amy, Michie, Patricia T., Michopolous, Vasiliki, Molina, Esther, Molto, Maria D., Munir, Asim, Muntane, Gerard, Naeem, Farooq, Nancarrow, Derek J., Nasar, Amina, Nasr, Tanvir, Ohaeri, Jude U., Ott, Jurg, Pantelis, Christos, Periyasamy, Sathish, Pinto, Ana G., Powers, Abigail, Ramos, Belen, Rana, Nusrat H., Rapaport, Mark, Reichenberg, Abraham, Saker-Delye, Safaa, Schall, Ulrich, Schofield, Peter R., Scott, Rodney J., Shanahan, Megan, Weickert, Cynthia Shannon, Sjaarda, Calvin, Smith, Heather J., Suarez-Rama, Jose Javier, Tariq, Muhammad, Thibaut, Florence, Tooney, Paul A., Umar, Muhammad, Vilella, Elisabet, Weiser, Mark, Wu, Jin Qin, Yolken, Robert

المساهمون: Institute for Molecular Medicine Finland

مصطلحات موضوعية: Genome-wide association, Of-function variants, Mutations, Metaanalysis, Burden, Individuals, Ancestry, Disorder, African, Setd1a, 1184 Genetics, developmental biology, physiology

الوصف: Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes(1). This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 x 10(-6)). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations. ; Peer reviewed

وصف الملف: application/pdf

العلاقة: Liu , D , Meyer , D , Fennessy , B , Feng , C , Cheng , E , Johnson , J , Park , Y J , Rieder , M-K , Ascolillo , S , de Pins , A , Dobbyn , A , Lebovitch , D , Moya , E , Nguyen , T-H , Wilkins , L , Hassan , A , Aghanwa , H , Burdick , K E , Buxbaum , J D , Domenici , E , Frangou , S , Hartmann , A M , Laurent-Levinson , C , Malhotra , D , Pato , C N , Pato , M T , Ressler , K , Roussos , P , Rujescu , D , Arango , C , Bertolino , A , Blasi , G , Bocchio-Chiavetto , L , Campion , D , Carr , V , Fullerton , J M , Gennarelli , M , Gonzalez-Penas , J , Levinson , D F , Mowry , B , Nimgaokar , V L , Pergola , G , Rampino , A , Cervilla , J A , Rivera , M , Schwab , S G , Wildenauer , D B , Daly , M , Neale , B , Singh , T , O'Donovan , M C , Owen , M J , Walters , J T , Ayub , M , Malhotra , A K , Lencz , T , Sullivan , P F , Sklar , P , Stahl , E A , Huckins , L M , Charney , A W , Aghanwa , H S , Ansari , M , Asif , A , Aslam , R , Ayuso , J L , Bigdeli , T , Bignotti , S , Bobes , J , Bradley , B , Buckley , P , Cairns , M J , Catts , S V , Chaudhry , A R , Cohen , D , Collins , B L , Consoli , A , Costas , J , Crespo-Facorro , B , Daskalakis , N P , Davidson , M , Davis , K L , Dickerson , F , Dogar , I A , Drapeau , E , Fananas , L , Fanous , A , Fatima , W , Fatjo , M , Filippich , C , Friedman , J , Fullard , J F , Georgakopoulos , P , Giannitelli , M , Giegling , I , Green , M J , Guillin , O , Gutierrez , B , Handoko , H Y , Hansen , S K , Haroon , M , Haroutunian , V , Henskens , F A , Hussain , F , Jablensky , A V , Junejo , J , Kelly , B J , Khan , S-U-D A , Khan , M N S , Khan , A , Khawaja , H R , Khizar , B , Kleopoulos , S P , Knowles , J , Konte , B , Kusumawardhani , A A A A , Leghari , N , Liu , X , Lori , A , Loughland , C M , Mahmood , K , Mahmood , S , Malaspina , D , Malik , D , McNaughton , A , Michie , P T , Michopolous , V , Molina , E , Molto , M D , Munir , A , Muntane , G , Naeem , F , Nancarrow , D J , Nasar , A , Nasr , T , Ohaeri , J U , Ott , J , Pantelis , C , Periyasamy , S , Pinto , A G , Powers , A , Ramos , B , Rana , N H , Rapaport , M , Reichenberg , A , Saker-Delye , S , Schall , U , Schofield , P R , Scott , R J , Shanahan , M , Weickert , C S , Sjaarda , C , Smith , H J , Suarez-Rama , J J , Tariq , M , Thibaut , F , Tooney , P A , Umar , M , Vilella , E , Weiser , M , Wu , J Q & Yolken , R 2023 , ' Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations ' , Nature Genetics , vol. 55 , no. 3 , pp. 369-+ . https://doi.org/10.1038/s41588-023-01305-1Test; 10c5c8b6-c641-4511-bc47-14cdf63cbe23; http://hdl.handle.net/10138/564219Test; 001021322000010

الإتاحة: http://hdl.handle.net/10138/564219Test

المؤلفون: Maury, Eduardo A., Sherman, Maxwell A., Genovese, Giulio, Gilgenast, Thomas G., Kamath, Tushar, Burris, S.J., Rajarajan, Prashanth, Flaherty, Erin, Akbarian, Schahram, Chess, Andrew, McCarroll, Steven A., Loh, Po-Ru, Phillips-Cremins, Jennifer E., Brennand, Kristen J., Macosko, Evan Z., Walters, James T.R., O'Donovan, Michael, Sullivan, Patrick, Sebat, Jonathan, Lee, Eunjung A., Walsh, Christopher A., Marshall, Christian R., Merico, Daniele, Thiruvahindrapuram, Bhooma, Wang, Zhouzhi, Scherer, Stephen W., Howrigan, Daniel P, Ripke, Stephan, Bulik-Sullivan, Brendan, Farh, Kai-How, Fromer, Menachem, Goldstein, Jacqueline I., Huang, Hailiang, Lee, Phil, Daly, Mark J., Neale, Benjamin M., Belliveau, Richard A., Bergen, Sarah E., Bevilacqua, Elizabeth, Chambert, Kimberley D., O'Dushlaine, Colm, Scolnick, Edward M., Smoller, Jordan W., Moran, Jennifer L., Palotie, Aarno, Petryshen, Tracey L., Wu, Wenting, Greer, Douglas S., Antaki, Danny, Shetty, Aniket, Gujral, Madhusudan, Brandler, William M., Malhotra, Dheeraj, Fuentes Fajarado, Karin V., Maile, Michelle S., Holmans, Peter A., Carrera, Noa, Craddock, Nick, Escott-Price, Valentina, Georgieva, Lyudmila, Hamshere, Marian L., Kavanagh, David, Legge, Sophie E., Pocklington, Andrew J., Richards, Alexander L., Ruderfer, Douglas M., Williams, Nigel M., Kirov, George, Owen, Michael J., Pinto, Dalila, Cai, Guiqing, Davis, Kenneth L., Drapeau, Elodie, Friedman, Joseph I, Haroutunian, Vahram, Parkhomenko, Elena, Reichenberg, Abraham, Silverman, Jeremy M., Buxbaum, Joseph D., Domenici, Enrico, Agartz, Ingrid, Djurovic, Srdjan, Mattingsdal, Morten, Melle, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Söderman, Erik, Albus, Margot, Alexander, Madeline, Laurent, Claudine, Levinson, Douglas F., Amin, Farooq, Atkins, Joshua, Cairns, Murray J., Scott, Rodney J., Tooney, Paul A., Wu, Jing Qin, Bacanu, Silviu A., Bigdeli, Tim B., Reimers, Mark A., Webb, Bradley T., Wolen, Aaron R., Wormley, Brandon K., Kendler, Kenneth S., Riley, Brien P., Kähler, Anna K., Magnusson, Patrik K.E., Hultman, Christina M., Bertalan, Marcelo, Hansen, Thomas, Olsen, Line, Rasmussen, Henrik B., Werge, Thomas, Mattheisen, Manuel, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Roffman, Joshua L., Byerley, William, Cahn, Wiepke, Kahn, René S, Strengman, Eric, Ophoff, Roel A., Carr, Vaughan J., Catts, Stanley V., Henskens, Frans A., Loughland, Carmel M., Michie, Patricia T., Pantelis, Christos, Schall, Ulrich, Jablensky, Assen V., Kelly, Brian J., Campion, Dominique, Cantor, Rita M., Cheng, Wei, Cloninger, C. Robert, Svrakic, Dragan M, Cohen, David, Cormican, Paul, Donohoe, Gary, Morris, Derek W., Corvin, Aiden, Gill, Michael, Crespo-Facorro, Benedicto, Crowley, James J., Farrell, Martilias S., Giusti-Rodríguez, Paola, Kim, Yunjung, Szatkiewicz, Jin P., Williams, Stephanie, Curtis, David, Pimm, Jonathan, Gurling, Hugh, McQuillin, Andrew, Davidson, Michael, Weiser, Mark, Degenhardt, Franziska, Forstner, Andreas J., Herms, Stefan, Hoffmann, Per, Hofman, Andrea, Cichon, Sven, Nöthen, Markus M., Del Favero, Jurgen, DeLisi, Lynn E., McCarley, Robert W., Levy, Deborah L., Mesholam-Gately, Raquelle I., Seidman, Larry J., Dikeos, Dimitris, Papadimitriou, George N., Dinan, Timothy, Duan, Jubao, Sanders, Alan R., Gejman, Pablo V., Gershon, Elliot S., Dudbridge, Frank, Eichhammer, Peter, Eriksson, Johan, Salomaa, Veikko, Essioux, Laurent, Fanous, Ayman H., Knowles, James A., Pato, Michele T., Pato, Carlos N., Frank, Josef, Meier, Sandra, Schulze, Thomas G., Strohmaier, Jana, Witt, Stephanie H., Rietschel, Marcella, Franke, Lude, Karjalainen, Juha, Freedman, Robert, Olincy, Ann, Freimer, Nelson B., Purcell, Shaun M., Roussos, Panos, Stahl, Eli A., Sklar, Pamela, Giegling, Ina, Hartmann, Annette M., Konte, Bettina, Rujescu, Dan, Godard, Stephanie, Hirschhorn, Joel N., Pers, Tune H., Price, Alkes, Esko, Tõnu, Gratten, Jacob, Lee, S. Hong, Visscher, Peter M., Wray, Naomi R., Mowry, Bryan J., de Haan, Lieuwe, Meijer, Carin J., Hansen, Mark, Ikeda, Masashi, Iwata, Nakao, Joa, Inge, Kalaydjieva, Luba, Keller, Matthew C., Kennedy, James L., Zai, Clement C., Knight, Jo, Lerer, Bernard, Liang, Kung-Yee, Lieberman, Jeffrey, Stroup, T. Scott, Lönnqvist, Jouko, Suvisaari, Jaana, Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, McDonald, Colm, McIntosh, Andrew M., Blackwood, Douglas H.R., Metspalu, Andres, Milani, Lili, Milanova, Vihra, Mokrab, Younes, Collier, David A., Müller-Myhsok, Bertram, Murphy, Kieran C., Murray, Robin M., Powell, John, Myin-Germeys, Inez, Van Os, Jim, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Pulver, Ann E., Nicodemus, Kristin K., Nisenbaum, Laura, Nordin, Annelie, Adolfsson, Rolf, O'Callaghan, Eadbhard, Oh, Sang-Yun, O'Neill, F. Anthony, Paunio, Tiina, Pietiläinen, Olli, Perkins, Diana O., Quested, Digby, Savitz, Adam, Li, Qingqin S., Schwab, Sibylle G., Shi, Jianxin, Spencer, Chris C.A., Thirumalai, Srinivas, Veijola, Juha, Waddington, John, Walsh, Dermot, Wildenauer, Dieter B., Bramon, Elvira, Darvasi, Ariel, Posthuma, Danielle, St. Clair, David, Shanta, Omar, Klein, Marieke, Park, Peter J., Weinberger, Daniel, Moran, John V., Gage, Fred H., Vaccarino, Flora M., Gleeson, Joseph, Mathern, Gary, Courchesne, Eric, Roy, Subhojit, Bizzotto, Sara, Coulter, Michael, Dias, Caroline, D'Gama, Alissa, Ganz, Javier, Hill, Robert, Huang, August Yue, Khoshkhoo, Sattar, Kim, Sonia, Lodato, Michael, Miller, Michael, Borges-Monroy, Rebeca, Rodin, Rachel, Zhou, Zinan, Bohrson, Craig, Chu, Chong, Cortes-Ciriano, Isidro, Dou, Yanmei, Galor, Alon, Gulhan, Doga, Kwon, Minseok, Luquette, Joe, Viswanadham, Vinay, Jones, Attila, Rosenbluh, Chaggai, Cho, Sean, Langmead, Ben, Thorpe, Jeremy, Erwin, Jennifer, Jaffe, Andrew, McConnell, Michael, Narurkar, Rujuta, Paquola, Apua, Shin, Jooheon, Straub, Richard, Abyzov, Alexej, Bae, Taejeong, Jang, Yeongjun, Wang, Yifan, Gage, Fred, Linker, Sara, Reed, Patrick, Wang, Meiyan, Urban, Alexander, Zhou, Bo, Zhu, Xiaowei, Pattni, Reenal, Amero, Aitor Serres, Juan, David, Lobon, Irene, Marques-Bonet, Tomas, Moruno, Manuel Solis, Perez, Raquel Garcia, Povolotskaya, Inna, Soriano, Eduardo, Averbuj, Dan, Ball, Laurel, Breuss, Martin, Yang, Xiaoxu, Chung, Changuk, Emery, Sarah B., Flasch, Diane A., Kidd, Jeffrey M., Kopera, Huira C., Kwan, Kenneth Y., Mills, Ryan E., Moldovan, John B., Sun, Chen, Zhao, Xuefang, Zhou, Weichen, Frisbie, Trenton J., Cherskov, Adriana, Fasching, Liana, Jourdon, Alexandre, Pochareddy, Sirisha, Scuderi, Soraya, Sestan, Nenad

الوصف: While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk.

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/166823/1/Schizophrenia-associated%20somatic%20copy-number.pdfTest; Maury, Eduardo A., Sherman, Maxwell A., Genovese, Giulio, Gilgenast, Thomas G., Kamath, Tushar, Burris, S.J., Rajarajan, Prashanth, Flaherty, Erin, Akbarian, Schahram, Chess, Andrew, McCarroll, Steven A., Loh, Po-Ru, Phillips-Cremins, Jennifer E., Brennand, Kristen J., Macosko, Evan Z., Walters, James T.R. https://orca.cardiff.ac.uk/view/cardiffauthors/A0230062.htmlTest orcid:0000-0002-6980-4053 orcid:0000-0002-6980-4053, O'Donovan, Michael https://orca.cardiff.ac.uk/view/cardiffauthors/A038895E.htmlTest orcid:0000-0001-7073-2379 orcid:0000-0001-7073-2379, Sullivan, Patrick, Sebat, Jonathan, Lee, Eunjung A., Walsh, Christopher A., Marshall, Christian R., Merico, Daniele, Thiruvahindrapuram, Bhooma, Wang, Zhouzhi, Scherer, Stephen W., Howrigan, Daniel P, Ripke, Stephan, Bulik-Sullivan, Brendan, Farh, Kai-How, Fromer, Menachem, Goldstein, Jacqueline I., Huang, Hailiang, Lee, Phil, Daly, Mark J., Neale, Benjamin M., Belliveau, Richard A., Bergen, Sarah E., Bevilacqua, Elizabeth, Chambert, Kimberley D., O'Dushlaine, Colm, Scolnick, Edward M., Smoller, Jordan W., Moran, Jennifer L., Palotie, Aarno, Petryshen, Tracey L., Wu, Wenting, Greer, Douglas S., Antaki, Danny, Shetty, Aniket, Gujral, Madhusudan, Brandler, William M., Malhotra, Dheeraj, Fuentes Fajarado, Karin V., Maile, Michelle S., Holmans, Peter A., Carrera, Noa, Craddock, Nick, Escott-Price, Valentina, Georgieva, Lyudmila, Hamshere, Marian L., Kavanagh, David, Legge, Sophie E., Pocklington, Andrew J., Richards, Alexander L., Ruderfer, Douglas M., Williams, Nigel M., Kirov, George, Owen, Michael J., Pinto, Dalila, Cai, Guiqing, Davis, Kenneth L., Drapeau, Elodie, Friedman, Joseph I, Haroutunian, Vahram, Parkhomenko, Elena, Reichenberg, Abraham, Silverman, Jeremy M., Buxbaum, Joseph D., Domenici, Enrico, Agartz, Ingrid, Djurovic, Srdjan, Mattingsdal, Morten, Melle, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Söderman, Erik, Albus, Margot, Alexander, Madeline, Laurent, Claudine, Levinson, Douglas F., Amin, Farooq, Atkins, Joshua, Cairns, Murray J., Scott, Rodney J., Tooney, Paul A., Wu, Jing Qin, Bacanu, Silviu A., Bigdeli, Tim B., Reimers, Mark A., Webb, Bradley T., Wolen, Aaron R., Wormley, Brandon K., Kendler, Kenneth S., Riley, Brien P., Kähler, Anna K., Magnusson, Patrik K.E., Hultman, Christina M., Bertalan, Marcelo, Hansen, Thomas, Olsen, Line, Rasmussen, Henrik B., Werge, Thomas, Mattheisen, Manuel, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Roffman, Joshua L., Byerley, William, Cahn, Wiepke, Kahn, René S, Strengman, Eric, Ophoff, Roel A., Carr, Vaughan J., Catts, Stanley V., Henskens, Frans A., Loughland, Carmel M., Michie, Patricia T., Pantelis, Christos, Schall, Ulrich, Jablensky, Assen V., Kelly, Brian J., Campion, Dominique, Cantor, Rita M., Cheng, Wei, Cloninger, C. Robert, Svrakic, Dragan M, Cohen, David, Cormican, Paul, Donohoe, Gary, Morris, Derek W., Corvin, Aiden, Gill, Michael, Crespo-Facorro, Benedicto, Crowley, James J., Farrell, Martilias S., Giusti-Rodríguez, Paola, Kim, Yunjung, Szatkiewicz, Jin P., Williams, Stephanie, Curtis, David, Pimm, Jonathan, Gurling, Hugh, McQuillin, Andrew, Davidson, Michael, Weiser, Mark, Degenhardt, Franziska, Forstner, Andreas J., Herms, Stefan, Hoffmann, Per, Hofman, Andrea, Cichon, Sven, Nöthen, Markus M., Del Favero, Jurgen, DeLisi, Lynn E., McCarley, Robert W., Levy, Deborah L., Mesholam-Gately, Raquelle I., Seidman, Larry J., Dikeos, Dimitris, Papadimitriou, George N., Dinan, Timothy, Duan, Jubao, Sanders, Alan R., Gejman, Pablo V., Gershon, Elliot S., Dudbridge, Frank, Eichhammer, Peter, Eriksson, Johan, Salomaa, Veikko, Essioux, Laurent, Fanous, Ayman H., Knowles, James A., Pato, Michele T., Pato, Carlos N., Frank, Josef, Meier, Sandra, Schulze, Thomas G., Strohmaier, Jana, Witt, Stephanie H., Rietschel, Marcella, Franke, Lude, Karjalainen, Juha, Freedman, Robert, Olincy, Ann, Freimer, Nelson B., Purcell, Shaun M., Roussos, Panos, Stahl, Eli A., Sklar, Pamela, Smoller, Jordan W., Giegling, Ina, Hartmann, Annette M., Konte, Bettina, Rujescu, Dan, Godard, Stephanie, Hirschhorn, Joel N., Pers, Tune H., Price, Alkes, Esko, Tõnu, Gratten, Jacob, Lee, S. Hong, Visscher, Peter M., Wray, Naomi R., Mowry, Bryan J., de Haan, Lieuwe, Meijer, Carin J., Hansen, Mark, Ikeda, Masashi, Iwata, Nakao, Joa, Inge, Kalaydjieva, Luba, Keller, Matthew C., Kennedy, James L., Zai, Clement C., Knight, Jo, Lerer, Bernard, Liang, Kung-Yee, Lieberman, Jeffrey, Stroup, T. Scott, Lönnqvist, Jouko, Suvisaari, Jaana, Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, McDonald, Colm, McIntosh, Andrew M., Blackwood, Douglas H.R., Metspalu, Andres, Milani, Lili, Milanova, Vihra, Mokrab, Younes, Collier, David A., Müller-Myhsok, Bertram, Murphy, Kieran C., Murray, Robin M., Powell, John, Myin-Germeys, Inez, Van Os, Jim, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Pulver, Ann E., Nicodemus, Kristin K., Nisenbaum, Laura, Nordin, Annelie, Adolfsson, Rolf, O'Callaghan, Eadbhard, Oh, Sang-Yun, O'Neill, F. Anthony, Paunio, Tiina, Pietiläinen, Olli, Perkins, Diana O., Quested, Digby, Savitz, Adam, Li, Qingqin S., Schwab, Sibylle G., Shi, Jianxin, Spencer, Chris C.A., Thirumalai, Srinivas, Veijola, Juha, Waddington, John, Walsh, Dermot, Wildenauer, Dieter B., Bramon, Elvira, Darvasi, Ariel, Posthuma, Danielle, St. Clair, David, Shanta, Omar, Klein, Marieke, Park, Peter J., Weinberger, Daniel, Moran, John V., Gage, Fred H., Vaccarino, Flora M., Gleeson, Joseph, Mathern, Gary, Courchesne, Eric, Roy, Subhojit, Bizzotto, Sara, Coulter, Michael, Dias, Caroline, D'Gama, Alissa, Ganz, Javier, Hill, Robert, Huang, August Yue, Khoshkhoo, Sattar, Kim, Sonia, Lodato, Michael, Miller, Michael, Borges-Monroy, Rebeca, Rodin, Rachel, Zhou, Zinan, Bohrson, Craig, Chu, Chong, Cortes-Ciriano, Isidro, Dou, Yanmei, Galor, Alon, Gulhan, Doga, Kwon, Minseok, Luquette, Joe, Viswanadham, Vinay, Jones, Attila, Rosenbluh, Chaggai, Cho, Sean, Langmead, Ben, Thorpe, Jeremy, Erwin, Jennifer, Jaffe, Andrew, McConnell, Michael, Narurkar, Rujuta, Paquola, Apua, Shin, Jooheon, Straub, Richard, Abyzov, Alexej, Bae, Taejeong, Jang, Yeongjun, Wang, Yifan, Gage, Fred, Linker, Sara, Reed, Patrick, Wang, Meiyan, Urban, Alexander, Zhou, Bo, Zhu, Xiaowei, Pattni, Reenal, Amero, Aitor Serres, Juan, David, Lobon, Irene, Marques-Bonet, Tomas, Moruno, Manuel Solis, Perez, Raquel Garcia, Povolotskaya, Inna, Soriano, Eduardo, Antaki, Danny, Averbuj, Dan, Ball, Laurel, Breuss, Martin, Yang, Xiaoxu, Chung, Changuk, Emery, Sarah B., Flasch, Diane A., Kidd, Jeffrey M., Kopera, Huira C., Kwan, Kenneth Y., Mills, Ryan E., Moldovan, John B., Sun, Chen, Zhao, Xuefang, Zhou, Weichen, Frisbie, Trenton J., Cherskov, Adriana, Fasching, Liana, Jourdon, Alexandre, Pochareddy, Sirisha, Scuderi, Soraya and Sestan, Nenad 2023. Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions. Cell Genomics 3 (8) , 100356. 10.1016/j.xgen.2023.100356 https://doi.org/10.1016/j.xgen.2023.100356Test file https://orca.cardiff.ac.uk/id/eprint/166823/1/Schizophrenia-associated%20somatic%20copy-number.pdfTest

الإتاحة: https://doi.org/10.1016/j.xgen.2023.100356Test
https://orca.cardiff.ac.uk/id/eprint/166823Test/
https://orca.cardiff.ac.uk/id/eprint/166823/1/Schizophrenia-associated%20somatic%20copy-number.pdfTest

المؤلفون: Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M.C., van Haren, Neeltje E.M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, de la Foz, Víctor Ortiz-García, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars Tjelta, Agartz, Ingrid, Andreassen, Ole, Jönsson, Erik Gunnar, Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T.J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Gur, Ruben C., Glahn, David C., Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen, Thompson, Paul M., Medland, Sarah E., Turner, Jessica A., van Erp, Theo G.M., Francks, Clyde

المصدر: 0027-8424.

الوصف: Left–right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case–control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case–control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case–control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case–control status. Subtle case–control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

العلاقة: Schijven, Dick Postema, Merel C. Fukunaga, Masaki Matsumoto, Junya Miura, Kenichiro de Zwarte, Sonja M.C. van Haren, Neeltje E.M. Cahn, Wiepke Hulshoff Pol, Hilleke E. Kahn, René S. Ayesa-Arriola, Rosa de la Foz, Víctor Ortiz-García Tordesillas-Gutierrez, Diana Vázquez-Bourgon, Javier Crespo-Facorro, Benedicto Alnæs, Dag Dahl, Andreas Westlye, Lars Tjelta Agartz, Ingrid Andreassen, Ole Jönsson, Erik Gunnar Kochunov, Peter Bruggemann, Jason M. Catts, Stanley V. Michie, Patricia T. Mowry, Bryan J. Quidé, Yann Rasser, Paul E. Schall, Ulrich Scott, Rodney J. Carr, Vaughan J. Green, Melissa J. Henskens, Frans A. Loughland, Carmel M. Pantelis, Christos Weickert, Cynthia Shannon Weickert, Thomas W. de Haan, Lieuwe Brosch, Katharina Pfarr, Julia-Katharina Ringwald, Kai G. Stein, Frederike Jansen, Andreas Kircher, Tilo T.J. Nenadić, Igor Krämer, Bernd Gruber, Oliver Satterthwaite, Theodore D. Bustillo, Juan Mathalon, Daniel H. Preda, Adrian Calhoun, Vince D. Ford, Judith M. Potkin, Steven G. Chen, Jingxu Tan, Yunlong Wang, Zhiren Xiang, Hong Fan, Fengmei Bernardoni, Fabio Ehrlich, Stefan Fuentes-Claramonte, Paola Garcia-Leon, Maria Angeles Guerrero-Pedraza, Amalia Salvador, Raymond Sarró, Salvador Pomarol-Clotet, Edith Ciullo, Valentina Piras, Fabrizio Vecchio, Daniela Banaj, Nerisa Spalletta, Gianfranco Michielse, Stijn van Amelsvoort, Therese Dickie, Erin W. Voineskos, Aristotle N. Sim, Kang Ciufolini, Simone Dazzan, Paola Murray, Robin M. Kim, Woo-Sung Chung, Young-Chul Andreou, Christina Schmidt, André Borgwardt, Stefan McIntosh, Andrew M. Whalley, Heather C. Lawrie, Stephen M. du Plessis, Stefan Luckhoff, Hilmar K. Scheffler, Freda Emsley, Robin Grotegerd, Dominik Lencer, Rebekka Dannlowski, Udo Edmond, Jesse T. Rootes-Murdy, Kelly Stephen, Julia M. Mayer, Andrew R. Antonucci, Linda A. Fazio, Leonardo Pergola, Giulio Bertolino, Alessandro Díaz-Caneja, Covadonga M. Janssen, Joost Lois, Noemi G. Arango, Celso Tomyshev, Alexander S. Lebedeva, Irina Cervenka, Simon Sellgren, Carl M. Georgiadis, Foivos Kirschner, Matthias Kaiser, Stefan Hajek, Tomas Skoch, Antonin Spaniel, Filip Kim, Minah Kwak, Yoo Bin Oh, Sanghoon Kwon, Jun Soo James, Anthony Bakker, Geor Knöchel, Christian Stäblein, Michael Oertel, Viola Uhlmann, Anne Howells, Fleur M. Stein, Dan J. Temmingh, Henk S. Diaz-Zuluaga, Ana M. Pineda-Zapata, Julian A. López-Jaramillo, Carlos Homan, Stephanie Ji, Ellen Surbeck, Werner Homan, Philipp Fisher, Simon E. Franke, Barbara Gur, Ruben C. Glahn, David C. Hashimoto, Ryota Jahanshad, Neda Luders, Eileen Thompson, Paul M. Medland, Sarah E. Turner, Jessica A. van Erp, Theo G.M. Francks, Clyde . Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium. Proceedings of the National Academy of Sciences of the United States of America. 2023, 120(14); http://hdl.handle.net/10852/106737Test; 2150697; info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Proceedings of the National Academy of Sciences of the United States of America&rft.volume=120&rft.spage=&rft.date=2023; Proceedings of the National Academy of Sciences of the United States of America; 120; 14; https://doi.org/10.1073/pnas.2213880120Test

الإتاحة: https://doi.org/10.1073/pnas.2213880120Test
http://hdl.handle.net/10852/106737Test

المؤلفون: Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy J., Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O’Donovan, Michael C., Walters, James T. R., Ripke, Stephan, Neale, Benjamin M., Farh, Kai-How, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A ., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C. K., Chen, Ronald Y. L., Chen, Eric Y. H., Cheng, Wei, Cheung, Eric F. C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Favero, Jurgen Del, DeLisi, Lynn E., Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Farrell, Martilias S., Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S., Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Haan, Lieuwe de, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Keong, Jimmy Lee Chee, Lee, S. Hong, Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K. E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O’Callaghan, Eadbhard, O’Dushlaine, Colm, O’Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Os, Jim Van, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Spencer, Chris C. A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H. M., Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Blackwood, Douglas H. R., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., Moran, Jennifer L., Nöthen, Markus M., Ophoff, Roel A., Palotie, Aarno, Petryshen, Tracey L., Posthuma, Danielle, Riley, Brien P., Sham, Pak C., Sklar, Pamela, Clair, David St, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Agbedjro, Deborah, Stahl, Daniel, Kapur, Shitij, Millgate, Edward, Kepinska, Adrianna, Kravariti, Eugenia, Ajnakina, Olesya, Alameda, Luis, Barnes, Thomas R. E., Berardi, Domenico, Bonora, Elena, Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D’Andrea, Giuseppe, Demjaha, Arsime, Do, Kim Q., Doody, Gillian A., Eap, Chin B., Ferchiou, Aziz, Di Forti, Marta, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen M., Kassoumeri, Laura, Khadimallah, Inès, Lastrina, Ornella, Muratori, Roberto, Noyan, Handan, O’Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Schürhoff, Franck, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Vázquez-Bourgon, Javier

مصطلحات موضوعية: Psychiatry and Mental health

الوصف: Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, Setting, and Participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10501) and individuals with non-TRS (n = 20325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main Outcomes and Measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85490 participants (48635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS ...

العلاقة: https://nottingham-repository.worktribe.com/output/7229725Test; JAMA Psychiatry; Volume 79; Issue 3; Pagination 260-269; https://nottingham-repository.worktribe.com/file/7229725/1/Jamapsychiatry%20Pardias%202022%20Oi%20210077%201640287782.06347Test

الإتاحة: https://doi.org/10.1001/jamapsychiatry.2021.3799Test
https://nottingham-repository.worktribe.com/file/7229725/1/Jamapsychiatry%20Pardias%202022%20Oi%20210077%201640287782.06347Test
https://nottingham-repository.worktribe.com/output/7229725Test

المؤلفون: Trubetskoy, Vassily, Pardiñas, Antonio F, Qi, Ting, Panagiotaropoulou, Georgia, Awasthi, Swapnil, Bigdeli, Tim B, Bryois, Julien, Chen, Chia-Yen, Dennison, Charlotte A, Hall, Lynsey S, Lam, Max, Watanabe, Kyoko, Frei, Oleksandr, Ge, Tian, Harwood, Janet C, Koopmans, Frank, Magnusson, Sigurdur, Richards, Alexander L, Sidorenko, Julia, Wu, Yang, Zeng, Jian, Grove, Jakob, Kim, Minsoo, Li, Zhiqiang, Voloudakis, Georgios, Zhang, Wen, Adams, Mark, Agartz, Ingrid, Atkinson, Elizabeth G, Agerbo, Esben, Al Eissa, Mariam, Albus, Margot, Alexander, Madeline, Alizadeh, Behrooz Z, Alptekin, Köksal, Als, Thomas D, Amin, Farooq, Arolt, Volker, Arrojo, Manuel, Athanasiu, Lavinia, Azevedo, Maria Helena, Bacanu, Silviu A, Bass, Nicholas J, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Benyamin, Beben, Bergen, Sarah E, Blasi, Giuseppe, Bobes, Julio, Bonassi, Stefano, Braun, Alice, Bressan, Rodrigo Affonseca, Bromet, Evelyn J, Bruggeman, Richard, Buckley, Peter F, Buckner, Randy L, Bybjerg-Grauholm, Jonas, Cahn, Wiepke, Cairns, Murray J, Calkins, Monica E, Carr, Vaughan J, Castle, David, Catts, Stanley V, Chambert, Kimberley D, Chan, Raymond CK, Chaumette, Boris, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cohen, David, Consoli, Angèle, Cordeiro, Quirino, Costas, Javier, Curtis, Charles, Davidson, Michael, Davis, Kenneth L, de Haan, Lieuwe, Degenhardt, Franziska, DeLisi, Lynn E, Demontis, Ditte, Dickerson, Faith, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Duan, Jubao, Ducci, Giuseppe, Dudbridge, Frank, Eriksson, Johan G, Fañanás, Lourdes, Faraone, Stephen V, Fiorentino, Alessia, Forstner, Andreas, Frank, Josef, Freimer, Nelson B, Fromer, Menachem, Frustaci, Alessandra, Gadelha, Ary, Genovese, Giulio, Gershon, Elliot S, Giannitelli, Marianna, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I, González Peñas, Javier, González-Pinto, Ana, Gopal, Srihari, Gratten, Jacob, Green, Michael F, Greenwood, Tiffany A, Guillin, Olivier, Gülöksüz, Sinan, Gur, Raquel E, Gur, Ruben C, Gutiérrez, Blanca, Hahn, Eric, Hakonarson, Hakon, Haroutunian, Vahram, Hartmann, Annette M, Harvey, Carol, Hayward, Caroline, Henskens, Frans A, Herms, Stefan, Hoffmann, Per, Howrigan, Daniel P, Ikeda, Masashi, Iyegbe, Conrad, Joa, Inge, Julià, Antonio, Kähler, Anna K, Kam-Thong, Tony, Kamatani, Yoichiro, Karachanak-Yankova, Sena, Kebir, Oussama, Keller, Matthew C, Kelly, Brian J, Khrunin, Andrey, Kim, Sung-Wan, Klovins, Janis, Kondratiev, Nikolay, Konte, Bettina, Kraft, Julia, Kubo, Michiaki, Kučinskas, Vaidutis, Kučinskiene, Zita Ausrele, Kusumawardhani, Agung, Kuzelova-Ptackova, Hana, Landi, Stefano, Lazzeroni, Laura C, Lee, Phil H, Legge, Sophie E, Lehrer, Douglas S, Lencer, Rebecca, Lerer, Bernard, Li, Miaoxin, Lieberman, Jeffrey, Light, Gregory A, Limborska, Svetlana, Liu, Chih-Min, Lönnqvist, Jouko, Loughland, Carmel M, Lubinski, Jan, Luykx, Jurjen J, Lynham, Amy, Macek, Milan, Mackinnon, Andrew, Magnusson, Patrik KE, Maher, Brion S, Maier, Wolfgang, Malaspina, Dolores, Mallet, Jacques, Marder, Stephen R, Marsal, Sara, Martin, Alicia R, Martorell, Lourdes, Mattheisen, Manuel, McCarley, Robert W, McDonald, Colm, McGrath, John J, Medeiros, Helena, Meier, Sandra, Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I, Metspalu, Andres, Michie, Patricia T, Milani, Lili, Milanova, Vihra, Mitjans, Marina, Molden, Espen, Molina, Esther, Molto, María Dolores, Mondelli, Valeria, Moreno, Carmen, Morley, Christopher P, Muntané, Gerard, Murphy, Kieran C, Myin-Germeys, Inez, Nenadić, Igor, Nestadt, Gerald, Nikitina-Zake, Liene, Noto, Cristiano, Nuechterlein, Keith H, O'Brien, Niamh Louise, O'Neill, F Anthony, Oh, Sang-Yun, Olincy, Ann, Ota, Vanessa Kiyomi, Pantelis, Christos, Papadimitriou, George N, Parellada, Mara, Paunio, Tiina, Pellegrino, Renata, Periyasamy, Sathish, Perkins, Diana O, Pfuhlmann, Bruno, Pietiläinen, Olli, Pimm, Jonathan, Porteous, David, Powell, John, Quattrone, Diego, Quested, Digby, Radant, Allen D, Rampino, Antonio, Rapaport, Mark H, Rautanen, Anna, Reichenberg, Abraham, Roe, Cheryl, Roffman, Joshua L, Roth, Julian, Rothermundt, Matthias, Rutten, Bart PF, Saker-Delye, Safaa, Salomaa, Veikko, Sanjuan, Julio, Santoro, Marcos Leite, Savitz, Adam, Schall, Ulrich, Scott, Rodney J, Seidman, Larry J, Sharp, Sally Isabel, Shi, Jianxin, Siever, Larry J, Sigurdsson, Engilbert, Sim, Kang, Skarabis, Nora, Slominsky, Petr, So, Hon-Cheong, Sobell, Janet L, Söderman, Erik, Stain, Helen J, Steen, Nils Eiel, Steixner-Kumar, Agnes A, Stögmann, Elisabeth, Stone, William S, Straub, Richard E, Streit, Fabian, Strengman, Eric, Stroup, T Scott, Subramaniam, Mythily, Sugar, Catherine A, Suvisaari, Jaana, Svrakic, Dragan M, Swerdlow, Neal R, Szatkiewicz, Jin P, Ta, Thi Minh Tam, Takahashi, Atsushi, Terao, Chikashi, Thibaut, Florence, Toncheva, Draga, Tooney, Paul A, Torretta, Silvia, Tosato, Sarah, Tura, Gian Battista, Turetsky, Bruce I, Üçok, Alp, Vaaler, Arne, van Amelsvoort, Therese, van Winkel, Ruud, Veijola, Juha, Waddington, John, Walter, Henrik, Waterreus, Anna, Webb, Bradley T, Weiser, Mark, Williams, Nigel M, Witt, Stephanie H, Wormley, Brandon K, Wu, Jing Qin, Xu, Zhida, Yolken, Robert, Zai, Clement C, Zhou, Wei, Zhu, Feng, Zimprich, Fritz, Atbaşoğlu, Eşref Cem, Ayub, Muhammad, Benner, Christian, Bertolino, Alessandro, Black, Donald W, Bray, Nicholas J, Breen, Gerome, Buccola, Nancy G, Byerley, William F, Chen, Wei J, Cloninger, C Robert, Crespo-Facorro, Benedicto, Donohoe, Gary, Freedman, Robert, Galletly, Cherrie, Gandal, Michael J, Gennarelli, Massimo, Hougaard, David M, Hwu, Hai-Gwo, Jablensky, Assen V, McCarroll, Steven A, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Müller-Myhsok, Bertram, Neil, Amanda L, Nordentoft, Merete, Pato, Michele T, Petryshen, Tracey L, Pirinen, Matti, Pulver, Ann E, Schulze, Thomas G, Silverman, Jeremy M, Smoller, Jordan W, Stahl, Eli A, Tsuang, Debby W, Vilella, Elisabet, Wang, Shi-Heng, Xu, Shuhua, Indonesia Schizophrenia Consortium, PsychENCODE, Psychosis Endophenotypes International Consortium, SynGO Consortium, Adolfsson, Rolf, Arango, Celso, Baune, Bernhard T, Belangero, Sintia Iole, Børglum, Anders D, Braff, David, Bramon, Elvira, Buxbaum, Joseph D, Campion, Dominique, Cervilla, Jorge A, Cichon, Sven, Collier, David A, Corvin, Aiden, Curtis, David, Forti, Marta Di, Domenici, Enrico, Ehrenreich, Hannelore, Escott-Price, Valentina, Esko, Tõnu, Fanous, Ayman H, Gareeva, Anna, Gawlik, Micha, Gejman, Pablo V, Gill, Michael, Glatt, Stephen J, Golimbet, Vera, Hong, Kyung Sue, Hultman, Christina M, Hyman, Steven E, Iwata, Nakao, Jönsson, Erik G, Kahn, René S, Kennedy, James L, Khusnutdinova, Elza, Kirov, George, Knowles, James A, Krebs, Marie-Odile, Laurent-Levinson, Claudine, Lee, Jimmy, Lencz, Todd, Levinson, Douglas F, Li, Qingqin S, Liu, Jianjun, Malhotra, Anil K, Malhotra, Dheeraj, McIntosh, Andrew, McQuillin, Andrew, Menezes, Paulo R, Morgan, Vera A, Morris, Derek W, Mowry, Bryan J, Murray, Robin M, Nimgaonkar, Vishwajit, Nöthen, Markus M, Ophoff, Roel A, Paciga, Sara A, Palotie, Aarno, Pato, Carlos N, Qin, Shengying, Rietschel, Marcella, Riley, Brien P, Rivera, Margarita, Rujescu, Dan, Saka, Meram C, Sanders, Alan R, Schwab, Sibylle G, Serretti, Alessandro, Sham, Pak C, Shi, Yongyong, St Clair, David, Stefánsson, Hreinn, Stefansson, Kari, Tsuang, Ming T, van Os, Jim, Vawter, Marquis P, Weinberger, Daniel R, Werge, Thomas, Wildenauer, Dieter B, Yu, Xin, Yue, Weihua, Holmans, Peter A, Pocklington, Andrew J, Roussos, Panos, Vassos, Evangelos, Verhage, Matthijs, Visscher, Peter M, Yang, Jian, Posthuma, Danielle, Andreassen, Ole A, Kendler, Kenneth S, Owen, Michael J, Wray, Naomi R, Daly, Mark J, Huang, Hailiang, Neale, Benjamin M, Sullivan, Patrick F, Ripke, Stephan, Walters, James TR, O'Donovan, Michael C, Schizophrenia Working Group of the Psychiatric Genomics Consorti

المصدر: Nature , 604 pp. 502-508. (2022)

مصطلحات موضوعية: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, ASSOCIATION, VARIANTS, INTEGRATION, DISEASE, ARCHITECTURE, INDIVIDUALS, STATISTICS, MUTATIONS, PROFILE, RISK

الوصف: Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10148396/1/PGC3%20SCZ%20Final%20Manuscript%20Part%201%20-%20Main%20text%20plus%20-%20flat%20-%2022.10.2021.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10148396/2/PGC3%20SCZ%20Final%20Manuscript%20Part%202%20-%20Methods%20plus%20-%20flat%2022.10.2021.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10148396Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10148396/1/PGC3%20SCZ%20Final%20Manuscript%20Part%201%20-%20Main%20text%20plus%20-%20flat%20-%2022.10.2021.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10148396/2/PGC3%20SCZ%20Final%20Manuscript%20Part%202%20-%20Methods%20plus%20-%20flat%2022.10.2021.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10148396Test/

المؤلفون: Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard, Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C.K., Chen, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric F.C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Lee Chee Keong, Jimmy, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O'Callaghan, Eadbhard, O'Dushlaine, Colm, O'Neill, F. Anthony, Oh, Sang Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, St Clair, David, Lencz, Todd, Mowry, Bryan J., Periyasamy, Sathish, Cairns, Murray J., Tooney, Paul A., Wu, Jing Qin, Kelly, Brian, Kirov, George, Sullivan, Patrick F., Riley, Brien P., Esko, Tõnu, Jönsson, Erik G., Palotie, Aarno, Ehrenreich, Hannelore, Steixner-Kumar, Agnes, Sham, Pak C., Iwata, Nakao, Weinberger, Daniel R., Gejman, Pablo V., Sanders, Alan R., Buxbaum, Joseph D., Rujescu, Dan, Bramon, Elvira, Pato, Michele T., Lee, Jimmy, Molden, Espen, Ophoff, Roel A., McQuillin, Andrew, Bass, Nicholas, Adolfsson, Rolf, Malhotra, Anil K., Stahl, Eli A., Breen, Gerome, Forstner, Andreas J., Trubetskoy, Vassily, Wang, Yunpeng, Coleman, Jonathan R.I., Gaspar, Héléna A., de Leeuw, Christiaan A., Steinberg, Stacy, Whitehead Pavlides, Jennifer M., Trzaskowski, Maciej, Byrne, Enda M., Richards, Alexander L., Abbott, Liam, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Bauer, Michael, Craig, David W., Gordon, Scott D., Green, Melissa J., Johnson, Jessica S., Li, Jun Z., Medland, Sarah E., Nguyen, Hoang, Rice, John P., Thompson, Robert C., Martin, Nicholas G., Schofield, Peter R., Adams, Mark J., Colodro-Conde, Lucía, Derks, Eske M., Gill, Michael, Howard, David M., Lind, Penelope A., Mehta, Divya, Nyholt, Dale R., Smith, Daniel J., Visscher, Peter M., other, and

المصدر: Biological Psychiatry

مصطلحات موضوعية: Bipolar disorder, Genome-wide association study, Genotype-by-sex interaction, Major depressive disorder, Schizophrenia, Sex differences

الوصف: Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10 −8 ), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10 −6 ) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10 −7 ; rs73033497, p = 8.8 × 10 −7 ; rs7914279, p = 6.4 × 10 −7 ), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10 −7 ) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10 −7 ), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10 −7 ) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, ...

وصف الملف: application/pdf

العلاقة: https://eprints.qut.edu.au/229995/1/108711064a.pdfTest; Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard, Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberly D., Chan, Raymond C.K., Chen, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric F.C., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Lee Chee Keong, Jimmy, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O'Callaghan, Eadbhard, O'Dushlaine, Colm, O'Neill, F. Anthony, Oh, Sang Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, St Clair, David, Lencz, Todd, Mowry, Bryan J., Periyasamy, Sathish, Cairns, Murray J., Tooney, Paul A., Wu, Jing Qin, Kelly, Brian, Kirov, George, Sullivan, Patrick F., Riley, Brien P., Esko, Tõnu, Jönsson, Erik G., Palotie, Aarno, Ehrenreich, Hannelore, Steixner-Kumar, Agnes, Sham, Pak C., Iwata, Nakao, Weinberger, Daniel R., Gejman, Pablo V., Sanders, Alan R., Buxbaum, Joseph D., Rujescu, Dan, Bramon, Elvira, Pato, Michele T., Lee, Jimmy, Molden, Espen, Ophoff, Roel A., McQuillin, Andrew, Bass, Nicholas, Adolfsson, Rolf, Malhotra, Anil K., Stahl, Eli A., Breen, Gerome, Forstner, Andreas J., Trubetskoy, Vassily, Wang, Yunpeng, Coleman, Jonathan R.I., Gaspar, Héléna A., de Leeuw, Christiaan A., Steinberg, Stacy, Whitehead Pavlides, Jennifer M., Trzaskowski, Maciej, Byrne, Enda M., Richards, Alexander L., Abbott, Liam, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Bauer, Michael, Craig, David W., Gordon, Scott D., Green, Melissa J., Johnson, Jessica S., Li, Jun Z., Medland, Sarah E., Nguyen, Hoang, Rice, John P., Thompson, Robert C., Martin, Nicholas G., Schofield, Peter R., Adams, Mark J., Colodro-Conde, Lucía, Derks, Eske M., Gill, Michael, Howard, David M., Lind, Penelope A., Mehta, Divya, Nyholt, Dale R., Smith, Daniel J., Visscher, Peter M., & other, and (2022) Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders. Biological Psychiatry, 91(1), pp. 102-117.; https://eprints.qut.edu.au/229995Test/; Centre for Data Science; Centre for Genomics and Personalised Health; Faculty of Science; Faculty of Health; School of Biomedical Sciences

الإتاحة: https://doi.org/10.1016/j.biopsych.2021.02.972Test
https://eprints.qut.edu.au/229995Test/

المؤلفون: Mehta, Divya, Tropf, Felix C, Gratten, Jacob, Bakshi, Andrew, Zhu, Zhihong, Bacanu, Silviu-Alin, Hemani, Gibran, Magnusson, Patrik KE, Barban, Nicola, Esko, Tõnu, Metspalu, Andres, Snieder, Harold, Mowry, Bryan J, Kendler, Kenneth S, Yang, Jian, Visscher, Peter M, McGrath, John J, Mills, Melinda C, Wray, Naomi R, Lee, S Hong, Andreassen, Ole A, Bramon, Elvira, Bruggeman, Richard, Buxbaum, Joseph D, Cairns, Murray J, Cantor, Rita M, Cloninger, C Robert, Cohen, David, Crespo-Facorro, Benedicto, Darvasi, Ariel, DeLisi, Lynn E, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Escott-Price, Valentina, Freimer, Nelson B, Georgieva, Lyudmila, de Haan, Lieuwe, Henskens, Frans A, Joa, Inge, Julià, Antonio, Khrunin, Andrey, Lerer, Bernard, Limborska, Svetlana, Loughland, Carmel M, Macek, Milan, Marsal, Sara, McCarley, Robert W, McIntosh, Andrew M, McQuillin, Andrew, Melegh, Bela, Michie, Patricia T, Morris, Derek W, Murphy, Kieran C, Myin-Germeys, Inez, Olincy, Ann, Van Os, Jim, Pantelis, Christos, Posthuma, Danielle, Quested, Digby, Schall, Ulrich, Scott, Rodney J, Seidman, Larry J, Toncheva, Draga, Tooney, Paul A, Waddington, John, Weinberger, Daniel R, Weiser, Mark, Wu, Jing Qin

المصدر: JAMA Psychiatry. 73(5)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Prevention, Brain Disorders, Serious Mental Illness, Mental Health, Schizophrenia, Clinical Research, Mental health, Adult, Alleles, Birth Order, Cohort Studies, Denmark, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Maternal Age, Phenotype, Pregnancy, Risk, Schizophrenia Working Group of the Psychiatric Genomics Consortium, LifeLines Cohort Study, and TwinsUK, Other Medical and Health Sciences, Psychology, Cognitive Sciences, Clinical sciences, Clinical and health psychology

الوصف: ImportanceA recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.ObjectiveTo determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.Design, setting, and participantsThis investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study.Main outcomes and measuresWe tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.ResultsWe observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring by McGrath et al in 2014.Conclusions and relevanceThis study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.

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الوصول الحر: https://escholarship.org/uc/item/0b2868b3Test

المؤلفون: Wall, Natalie G. (R21270), Smith, Oliver, Campbell, Linda E., Loughland, Carmel M., Wallis, Mark, Henskens, Frans, Schall, Ulrich

مصطلحات موضوعية: XXXXXX - Unknown

الوصف: Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals. One such difficulty is recognizing basic and complex facial expressions. Research has previously found that there are many evidence-based support programs available for building non-verbal communication skills. These programs are frequently administered with a therapist or in a group setting, making them inflexible in nature. Programs hosted on e-technology are becoming increasingly popular, with many parents supportive of them. Applications (apps) that are hosted on technology such as iPads or mobile phones allow users to engage in building skills in real-time social settings and own what they are learning. These technologies are frequently used by autistic children, with apps typically focusing on identifying facial features. Yet at this current time, there are mixed reviews of how to design such programs and what their theoretical backing is, with many studies using a mix of observation and psychological assessments as outcome measures. Eye-tracking and electroencephalography are established methodologies that measure neural processing and gaze behaviors while viewing faces. To better support the field moving forward, objective measures such as these are a way to measure outcomes of apps that are designed for helping children on the spectrum build skills in understanding facial expressions.

وصف الملف: print

العلاقة: World Journal of Psychiatry--2220-3206-- Vol. 11 Issue. 12 No. pp: 1239-1246

الإتاحة: https://doi.org/10.5498/wjp.v11.i12.1239Test
https://hdl.handle.net/1959.7/uws:75111Test

المؤلفون: Hess, Jonathan L., Tylee, Daniel S., Mattheisen, Manuel, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Børglum, Anders D., Als, Thomas D., Grove, Jakob, Werge, Thomas, Mortensen, Preben Bo, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Byberg-Grauholm, Jonas, Bækvad-Hansen, Maree, Greenwood, Tiffany A., Tsuang, Ming T., Curtis, David, Steinberg, Stacy, Sigurdsson, Engilbert, Stefánsson, Hreinn, Stefánsson, Kári, Edenberg, Howard J., Holmans, Peter, Faraone, Stephen V., Glatt, Steven J., Cairns, Murray J., Carr, Vaughan J., Henskens, Frans A., Kelly, Brian J., Loughland, Carmel M., Michie, Patricia T., Schall, Ulrich A, Scott, Rodney, Tooney, Paul

المساهمون: The University of Newcastle. Faculty of Health & Medicine, School of Biomedical Sciences and Pharmacy

مصطلحات موضوعية: genetics, schizophrenia

الوصف: Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder.

العلاقة: Molecular Psychiatry Vol. 26, Issue 3, p. 800-815; http://hdl.handle.net/1959.13/1425297Test; uon:38229

الإتاحة: http://hdl.handle.net/1959.13/1425297Test