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2. Impact of random alloy fluctuations on the carrier distribution in multi-color (In,Ga)N/GaN quantum well systems

Author

O'Donovan, Michael, Farrell, Patricio, Moatti, Julien, Streckenbach, Timo, Koprucki, Thomas, and Schulz, Stefan

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

In this work, we study the impact that random alloy fluctuations have on the distribution of electrons and holes across the active region of a (In,Ga)N/GaN multi-quantum well based light emitting diode (LED). To do so, an atomistic tight-binding model is employed to account for alloy fluctuations on a microscopic level and the resulting tight-binding energy landscape forms input to a drift-diffusion model. Here, quantum corrections are introduced via localization landscape theory and we show that when neglecting alloy disorder our theoretical framework yields results similar to commercial software packages that employ a self-consistent Schroedinger-Poisson-drift-diffusion solver. Similar to experimental studies in the literature, we have focused on a multi-quantum well system where two of the three wells have the same In content while the third well differs in In content. By changing the order of wells in this multicolor quantum well structure and looking at the relative radiative recombination rates of the different emitted wavelengths, we (i) gain insight into the distribution of carriers in such a system and (ii) can compare our findings to trends observed in experiment. Our results indicate that the distribution of carriers depends significantly on the treatment of the quantum well microstructure. When including random alloy fluctuations and quantum corrections in the simulations, the calculated trends in the relative radiative recombination rates as a function of the well ordering are consistent with previous experimental studies. The results from the widely employed virtual crystal approximation contradict the experimental data. Overall, our work highlights the importance of a careful and detailed theoretical description of the carrier transport in an (In,Ga)N/GaN multi-quantum well system to ultimately guide the design of the active region of III-N-based LED structures., Comment: 12 pages, 6 figures

Published
2022

4. Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD

Author

Wang, Sheng, Wang, Belinda, Drury, Vanessa, Drake, Sam, Sun, Nawei, Alkhairo, Hasan, Arbelaez, Juan, Duhn, Clif, Bal, Vanessa H., Langley, Kate, Martin, Joanna, Hoekstra, Pieter J., Dietrich, Andrea, Xing, Jinchuan, Heiman, Gary A., Tischfield, Jay A., Fernandez, Thomas V., Owen, Michael J., O’Donovan, Michael C., Thapar, Anita, State, Matthew W., and Willsey, A. Jeremy

Published
2023
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7. Multiscale simulations of uni-polar hole transport in (In,Ga)N quantum well systems

Author

O'Donovan, Michael, Farrell, Patricio, Streckenbach, Timo, Koprucki, Thomas, and Schulz, Stefan

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

Understanding the impact of the alloy micro-structure on carrier transport becomes important when designing III-nitride-based LED structures. In this work, we study the impact of alloy fluctuations on the hole carrier transport in (In,Ga)N single and multi-quantum well systems. To disentangle hole transport from electron transport and carrier recombination processes, we focus our attention on uni-polar (p-i-p) systems. The calculations employ our recently established multi-scale simulation framework that connects atomistic tight-binding theory with a macroscale drift-diffusion model. In addition to alloy fluctuations, we pay special attention to the impact of quantum corrections on hole transport. Our calculations indicate that results from a virtual crystal approximation present an upper limit for the hole transport in a p-i-p structure in terms of the current-voltage characteristics. Thus we find that alloy fluctuations can have a detrimental effect on hole transport in (In,Ga)N quantum well systems, in contrast to uni-polar electron transport. However, our studies also reveal that the magnitude by which the random alloy results deviate from virtual crystal approximation data depends on several factors, e.g. how quantum corrections are treated in the transport calculations., Comment: 13 pages, 12 figures, submitted to Optical and Quantum Electronics - Topical Collection for NUSOD 2021

Published
2021

8. How Real-World Data Can Facilitate the Development of Precision Medicine Treatment in Psychiatry

Author

Koch, Elise, Pardiñas, Antonio F., O’Connell, Kevin S., Selvaggi, Pierluigi, Camacho Collados, José, Babic, Aleksandar, Marshall, Serena E., Van der Eycken, Erik, Angulo, Cecilia, Lu, Yi, Sullivan, Patrick F., Dale, Anders M., Molden, Espen, Posthuma, Danielle, White, Nathan, Schubert, Alexander, Djurovic, Srdjan, Heimer, Hakon, Stefánsson, Hreinn, Stefánsson, Kári, Werge, Thomas, Sønderby, Ida, O’Donovan, Michael C., Walters, James T.R., Milani, Lili, and Andreassen, Ole A.

Published
2024
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9. Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

Author

Palmer, Duncan S, Howrigan, Daniel P, Chapman, Sinéad B, Adolfsson, Rolf, Bass, Nick, Blackwood, Douglas, Boks, Marco PM, Chen, Chia-Yen, Churchhouse, Claire, Corvin, Aiden P, Craddock, Nicholas, Curtis, David, Di Florio, Arianna, Dickerson, Faith, Freimer, Nelson B, Goes, Fernando S, Jia, Xiaoming, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene S, Landén, Mikael, Locke, Adam E, McIntosh, Andrew M, McQuillin, Andrew, Morris, Derek W, O’Donovan, Michael C, Ophoff, Roel A, Owen, Michael J, Pedersen, Nancy L, Posthuma, Danielle, Reif, Andreas, Risch, Neil, Schaefer, Catherine, Scott, Laura, Singh, Tarjinder, Smoller, Jordan W, Solomonson, Matthew, Clair, David St, Stahl, Eli A, Vreeker, Annabel, Walters, James TR, Wang, Weiqing, Watts, Nicholas A, Yolken, Robert, Zandi, Peter P, and Neale, Benjamin M

Subjects
Biotechnology, Human Genome, Clinical Research, Serious Mental Illness, Schizophrenia, Brain Disorders, Bipolar Disorder, Mental Health, Genetics, 2.1 Biological and endogenous factors, Aetiology, Mental health, A Kinase Anchor Proteins, Exome, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Exome Sequencing, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.

Published
2022

11. Accelerated Cortical Thinning in Schizophrenia Is Associated With Rare and Common Predisposing Variation to Schizophrenia and Neurodevelopmental Disorders

Author

González-Peñas, Javier, Díaz-Caneja, Covadonga M., Costas, Javier, Gurriarán, Xaquín, Andreu-Bernabeu, Álvaro, Fañanas, Lourdes, Rosa de la Cruz, Araceli, Arias, Bárbara, Bobes, Julio, Pinto, Ana González, Crespo-Facorro, B., Martorell, L., Vilella, Elisabet, Muntané, Gerard, Moltó, María Dolores, Escartí, María José, Rivero, Olga, Parellada, Mara, Moreno, Carmen, Arango, Celso, Alloza, Clara, Brouwer, Rachel, González-Lois, Noemí, Gallego, Ana Guil, de Hoyos, Lucía, Romero-García, Rafael, Fañanás, Lourdes, González-Pinto, Ana, Crespo-Facorro, Benedicto, Martorell, Lourdes, Arrojo, Manuel, Gutiérrez-Zotes, Alfonso, Perez-Rando, Marta, Buimer, Elizabeth, van Haren, Neeltje, Cahn, Wiepke, O’Donovan, Michael, Kahn, René S., Pol, Hilleke Hulshoff, Janssen, Joost, and Schnack, Hugo

Published
2024
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18. Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Author

Liu, Dongjing, Meyer, Dara, Fennessy, Brian, Feng, Claudia, Cheng, Esther, Johnson, Jessica S., Park, You Jeong, Rieder, Marysia-Kolbe, Ascolillo, Steven, de Pins, Agathe, Dobbyn, Amanda, Lebovitch, Dannielle, Moya, Emily, Nguyen, Tan-Hoang, Wilkins, Lillian, Hassan, Arsalan, 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, González-Peñas, 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., and Charney, Alexander W.

Published
2023
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21. Schizophrenia, autism spectrum disorders and developmental disorders share specific disruptive coding mutations.

Author

Rees, Elliott, Creeth, Hugo DJ, Hwu, Hai-Gwo, Chen, Wei J, Tsuang, Ming, Glatt, Stephen J, Rey, Romain, Kirov, George, Walters, James TR, Holmans, Peter, Owen, Michael J, and O'Donovan, Michael C

Subjects
Mental Health, Neurosciences, Genetics, Schizophrenia, Serious Mental Illness, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Pediatric, Autism, 2.1 Biological and endogenous factors, Mental health
Abstract

People with schizophrenia are enriched for rare coding variants in genes associated with neurodevelopmental disorders, particularly autism spectrum disorders and intellectual disability. However, it is unclear if the same changes to gene function that increase risk to neurodevelopmental disorders also do so for schizophrenia. Using data from 3444 schizophrenia trios and 37,488 neurodevelopmental disorder trios, we show that within shared risk genes, de novo variants in schizophrenia and neurodevelopmental disorders are generally of the same functional category, and that specific de novo variants observed in neurodevelopmental disorders are enriched in schizophrenia (P = 5.0 × 10-6). The latter includes variants known to be pathogenic for syndromic disorders, suggesting that schizophrenia be included as a characteristic of those syndromes. Our findings imply that, in part, neurodevelopmental disorders and schizophrenia have shared molecular aetiology, and therefore likely overlapping pathophysiology, and support the hypothesis that at least some forms of schizophrenia lie on a continuum of neurodevelopmental disorders.

Published
2021

22. Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

Author

Jia, Xiaoming, Goes, Fernando S, Locke, Adam E, Palmer, Duncan, Wang, Weiqing, Cohen-Woods, Sarah, Genovese, Giulio, Jackson, Anne U, Jiang, Chen, Kvale, Mark, Mullins, Niamh, Nguyen, Hoang, Pirooznia, Mehdi, Rivera, Margarita, Ruderfer, Douglas M, Shen, Ling, Thai, Khanh, Zawistowski, Matthew, Zhuang, Yongwen, Abecasis, Gonçalo, Akil, Huda, Bergen, Sarah, Burmeister, Margit, Chapman, Sinéad, DelaBastide, Melissa, Juréus, Anders, Kang, Hyun Min, Kwok, Pui-Yan, Li, Jun Z, Levy, Shawn E, Monson, Eric T, Moran, Jennifer, Sobell, Janet, Watson, Stanley, Willour, Virginia, Zöllner, Sebastian, Adolfsson, Rolf, Blackwood, Douglas, Boehnke, Michael, Breen, Gerome, Corvin, Aiden, Craddock, Nick, DiFlorio, Arianna, Hultman, Christina M, Landen, Mikael, Lewis, Cathryn, McCarroll, Steven A, Richard McCombie, W, McGuffin, Peter, McIntosh, Andrew, McQuillin, Andrew, Morris, Derek, Myers, Richard M, O'Donovan, Michael, Ophoff, Roel, Boks, Marco, Kahn, Rene, Ouwehand, Willem, Owen, Michael, Pato, Carlos, Pato, Michele, Posthuma, Danielle, Potash, James B, Reif, Andreas, Sklar, Pamela, Smoller, Jordan, Sullivan, Patrick F, Vincent, John, Walters, James, Neale, Benjamin, Purcell, Shaun, Risch, Neil, Schaefer, Catherine, Stahl, Eli A, Zandi, Peter P, and Scott, Laura J

Subjects
Humans, Genetic Predisposition to Disease, Bipolar Disorder, Schizophrenia, Polymorphism, Single Nucleotide, Genetic Variation, Genome-Wide Association Study, Exome, Brain Disorders, Prevention, Clinical Research, Human Genome, Serious Mental Illness, Genetics, Mental Health, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.

Published
2021

26. Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium

Author

Peterson, Roseann E, Bigdeli, Tim B, Ripke, Stephan, Bacanu, Silviu-Alin, Gejman, Pablo V, Levinson, Douglas F, Li, Qingqin S, Rujescu, Dan, Rietschel, Marcella, Weinberger, Daniel R, Straub, Richard E, Walters, James TR, Owen, Michael J, O'Donovan, Michael C, Mowry, Bryan J, Ophoff, Roel A, Andreassen, Ole A, Esko, Tõnu, Petryshen, Tracey L, Kendler, Kenneth S, Consortium, Schizophrenia Working Group of the Psychiatric Genomics, and Fanous, Ayman H

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Tobacco Smoke and Health, Substance Misuse, Prevention, Behavioral and Social Science, Biotechnology, Tobacco, Brain Disorders, Genetics, Mental Health, Serious Mental Illness, Human Genome, Mental health, Good Health and Well Being, Adult, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Membrane Proteins, Nerve Tissue Proteins, Phenotype, Polymorphism, Single Nucleotide, Smoking, GWAS, Smoking initiation, Cigarettes per day, Pleiotropy, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (rg = 0.159; P = 5.05 × 10-10), cigarettes-smoked-per-day (rg = 0.094; P = 0.006), and age-of-onset of smoking (rg = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg = 0.624, P = 0.002) and cigarettes-smoked-per-day (rg = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10-5) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10-8, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.

Published
2021

28. Genome-wide Association Analysis of Parkinson’s Disease and Schizophrenia Reveals Shared Genetic Architecture and Identifies Novel Risk Loci

Author

Smeland, Olav B, Shadrin, Alexey, Bahrami, Shahram, Broce, Iris, Tesli, Martin, Frei, Oleksandr, Wirgenes, Katrine V, O'Connell, Kevin S, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Sugrue, Leo, Wang, Yunpeng, Svenningsson, Per, Sharma, Manu, Pihlstrøm, Lasse, Toft, Mathias, O'Donovan, Michael, Djurovic, Srdjan, Desikan, Rahul, Dale, Anders M, and Andreassen, Ole A

Subjects
Genetics, Biotechnology, Aging, Parkinson's Disease, Neurodegenerative, Serious Mental Illness, Human Genome, Neurosciences, Prevention, Mental Health, Schizophrenia, Brain Disorders, 2.1 Biological and endogenous factors, Aetiology, Neurological, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Parkinson Disease, Polymorphism, Single Nucleotide, GWAS, Genetic overlap, Parkinson’s disease, RERE, ZDHHC2, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundParkinson's disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders.MethodsWe analyzed recent large genome-wide association studies on patients with SCZ (N = 77,096) and PD (N = 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci.ResultsWe observed genetic enrichment in PD conditional on associations with SCZ and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PD risk loci and 1 novel SCZ locus at conditional FDR < .01. Furthermore, we identified 9 genomic loci jointly associated with PD and SCZ at conjunctional FDR < .05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to the shared loci, 65 are expressed in the human brain and show cell type-specific expression profiles.ConclusionsAltogether, the study increases understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders.

Published
2021

29. Pathogenic Mis-splicing of CPEB4 in Schizophrenia

Author

Ollà, Ivana, Pardiñas, Antonio F., Parras, Alberto, Hernández, Ivó H., Santos-Galindo, María, Picó, Sara, Callado, Luis F., Elorza, Ainara, Rodríguez-López, Claudia, Fernández-Miranda, Gonzalo, Belloc, Eulàlia, Walters, James T.R., O’Donovan, Michael C., Méndez, Raúl, Toma, Claudio, Meana, J. Javier, Owen, Michael J., and Lucas, José J.

Published
2023
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30. Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

Author

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., Jr., 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, 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., and Walsh, Christopher A.

Published
2023
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32. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Author

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 A., Jr., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C.K., Chan, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric FC., 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, 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, 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, Andreassen, Ole A., 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., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Nöthen, Markus M., Ophoff, Roel A., Owen, Michael J., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F., O'Donovan, Michael C., Qin, Shengying, Sawa, Akira, Kahn, Rene, Hong, Kyung Sue, Shi, Wenzhao, Tsuang, Ming, Itokawa, Masanari, Feng, Gang, Glatt, Stephen J., Ma, Xiancang, Tang, Jinsong, Ruan, Yunfeng, Liu, Ruize, Zhu, Feng, Horiuchi, Yasue, Lee, Byung Dae, Joo, Eun-Jeong, Myung, Woojae, Ha, Kyooseob, Won, Hong-Hee, Baek, Ji Hyung, Chung, Young Chul, Kim, Sung-Wan, Kusumawardhani, Agung, Chen, Wei J., Hwu, Hai-Gwo, Hishimoto, Akitoyo, Otsuka, Ikuo, Sora, Ichiro, Toyota, Tomoko, Yoshikawa, Takeo, Kunugi, Hiroshi, Hattori, Kotaro, Ishiwata, Sayuri, Numata, Shusuke, Ohmori, Tetsuro, Arai, Makoto, Ozeki, Yuji, Fujii, Kumiko, Kim, Se Joo, Lee, Heon-Jeong, Ahn, Yong Min, Kim, Se Hyun, Akiyama, Kazufumi, Shimoda, Kazutaka, Kinoshita, Makoto, Hsu, Yu-Han H., Pintacuda, Greta, Nacu, Eugeniu, Kim, April, Tsafou, Kalliopi, Petrossian, Natalie, Crotty, William, Suh, Jung Min, Riseman, Jackson, Martin, Jacqueline M., Biagini, Julia C., Mena, Daya, Ching, Joshua K.T., Malolepsza, Edyta, Li, Taibo, Singh, Tarjinder, Ge, Tian, Egri, Shawn B., Tanenbaum, Benjamin, Stanclift, Caroline R., Apffel, Annie M., Carr, Steven A., Schenone, Monica, Jaffe, Jake, Fornelos, Nadine, Eggan, Kevin C., and Lage, Kasper

Published
2023
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33. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria Paz, Sanjuan, Julio, Escarti, Maria Jose, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Üçok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, van Os, Jim, Rutten, Bart PF, and Guloksuz, Sinan

Published
2023
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35. The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Author

Richards, Alexander L, Pardiñas, Antonio F, Frizzati, Aura, Tansey, Katherine E, Lynham, Amy J, Holmans, Peter, Legge, Sophie E, Savage, Jeanne E, Agartz, Ingrid, Andreassen, Ole A, Blokland, Gabriella AM, Corvin, Aiden, Cosgrove, Donna, Degenhardt, Franziska, Djurovic, Srdjan, Espeseth, Thomas, Ferraro, Laura, Gayer-Anderson, Charlotte, Giegling, Ina, van Haren, Neeltje E, Hartmann, Annette M, Hubert, John J, Jönsson, Erik G, Konte, Bettina, Lennertz, Leonhard, Olde Loohuis, Loes M, Melle, Ingrid, Morgan, Craig, Morris, Derek W, Murray, Robin M, Nyman, Håkan, Ophoff, Roel A, van Os, Jim, Petryshen, Tracey L, Quattrone, Diego, Rietschel, Marcella, Rujescu, Dan, Rutten, Bart PF, Streit, Fabian, Strohmaier, Jana, Sullivan, Patrick F, Sundet, Kjetil, Wagner, Michael, Escott-Price, Valentina, Owen, Michael J, Donohoe, Gary, O’Donovan, Michael C, and Walters, James TR

Subjects
Genetics, Prevention, Schizophrenia, Depression, Behavioral and Social Science, Mental Health, Brain Disorders, Serious Mental Illness, Human Genome, 2.1 Biological and endogenous factors, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Bipolar Disorder, Datasets as Topic, Depressive Disorder, Major, Educational Status, Genome-Wide Association Study, Humans, Intelligence, Multifactorial Inheritance, Psychotic Disorders, psychiatry, genomics, intelligence, bioinformatics, GROUP Investigators, EUGEI WP2 Group, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundCognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.MethodsWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.ResultsPRS for both population IQ (P = 4.39 × 10-28) and EA (P = 1.27 × 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.ConclusionsCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.

Published
2020

37. Comparative genetic architectures of schizophrenia in East Asian and European populations

Author

Lam, Max, Chen, Chia-Yen, Li, Zhiqiang, Martin, Alicia R, Bryois, Julien, Ma, Xixian, Gaspar, Helena, Ikeda, Masashi, Benyamin, Beben, Brown, Brielin C, Liu, Ruize, Zhou, Wei, Guan, Lili, Kamatani, Yoichiro, Kim, Sung-Wan, Kubo, Michiaki, Kusumawardhani, Agung AAA, Liu, Chih-Min, Ma, Hong, Periyasamy, Sathish, Takahashi, Atsushi, Xu, Zhida, Yu, Hao, Zhu, Feng, Chen, Wei J, Faraone, Stephen, Glatt, Stephen J, He, Lin, Hyman, Steven E, Hwu, Hai-Gwo, McCarroll, Steven A, Neale, Benjamin M, Sklar, Pamela, Wildenauer, Dieter B, Yu, Xin, Zhang, Dai, Mowry, Bryan J, Lee, Jimmy, Holmans, Peter, Xu, Shuhua, Sullivan, Patrick F, Ripke, Stephan, O’Donovan, Michael C, Daly, Mark J, Qin, Shengying, Sham, Pak, Iwata, Nakao, Hong, Kyung S, Schwab, Sibylle G, Yue, Weihua, Tsuang, Ming, Liu, Jianjun, Ma, Xiancang, Kahn, René S, Shi, Yongyong, and Huang, Hailiang

Subjects
Genetics, Human Genome, Serious Mental Illness, Schizophrenia, Brain Disorders, Mental Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Asian People, Case-Control Studies, Asia, Eastern, Genetics, Population, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, White People, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Indonesia Schizophrenia Consortium, Genetic REsearch on schizophreniA neTwork-China and the Netherlands, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.

Published
2019

41. Genetic and Phenotypic Features of Schizophrenia in the UK Biobank

Author

Legge, Sophie E., primary, Pardiñas, Antonio F., additional, Woolway, Grace, additional, Rees, Elliott, additional, Cardno, Alastair G., additional, Escott-Price, Valentina, additional, Holmans, Peter, additional, Kirov, George, additional, Owen, Michael J., additional, O’Donovan, Michael C., additional, and Walters, James T. R., additional

Published
2024
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42. Transcriptional programs regulating neuronal differentiation are disrupted in DLG2 knockout human embryonic stem cells and enriched for schizophrenia and related disorders risk variants

Author

Sanders, Bret, D’Andrea, Daniel, Collins, Mark O., Rees, Elliott, Steward, Tom G. J., Zhu, Ying, Chapman, Gareth, Legge, Sophie E., Pardiñas, Antonio F., Harwood, Adrian J., Gray, William P., O’Donovan, Michael C., Owen, Michael J., Errington, Adam C., Blake, Derek J., Whitcomb, Daniel J., Pocklington, Andrew J., and Shin, Eunju

Published
2022
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43. Mapping genomic loci implicates genes and synaptic biology in schizophrenia

Author

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 C. K., Chaumette, Boris, Cheng, Wei, Cheung, Eric F. C., 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, Jr, Milan, Mackinnon, Andrew, Magnusson, Patrik K. E., 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 P. F., 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, 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 T. R., and O’Donovan, Michael C.

Published
2022
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44. Rare coding variants in ten genes confer substantial risk for schizophrenia

Author

Singh, Tarjinder, Poterba, Timothy, Curtis, David, Akil, Huda, Al Eissa, Mariam, Barchas, Jack D., Bass, Nicholas, Bigdeli, Tim B., Breen, Gerome, Bromet, Evelyn J., Buckley, Peter F., Bunney, William E., Bybjerg-Grauholm, Jonas, Byerley, William F., Chapman, Sinéad B., Chen, Wei J., Churchhouse, Claire, Craddock, Nicholas, Cusick, Caroline M., DeLisi, Lynn, Dodge, Sheila, Escamilla, Michael A., Eskelinen, Saana, Fanous, Ayman H., Faraone, Stephen V., Fiorentino, Alessia, Francioli, Laurent, Gabriel, Stacey B., Gage, Diane, Gagliano Taliun, Sarah A., Ganna, Andrea, Genovese, Giulio, Glahn, David C., Grove, Jakob, Hall, Mei-Hua, Hämäläinen, Eija, Heyne, Henrike O., Holi, Matti, Hougaard, David M., Howrigan, Daniel P., Huang, Hailiang, Hwu, Hai-Gwo, Kahn, René S., Kang, Hyun Min, Karczewski, Konrad J., Kirov, George, Knowles, James A., Lee, Francis S., Lehrer, Douglas S., Lescai, Francesco, Malaspina, Dolores, Marder, Stephen R., McCarroll, Steven A., McIntosh, Andrew M., Medeiros, Helena, Milani, Lili, Morley, Christopher P., Morris, Derek W., Mortensen, Preben Bo, Myers, Richard M., Nordentoft, Merete, O’Brien, Niamh L., Olivares, Ana Maria, Ongur, Dost, Ouwehand, Willem H., Palmer, Duncan S., Paunio, Tiina, Quested, Digby, Rapaport, Mark H., Rees, Elliott, Rollins, Brandi, Satterstrom, F. Kyle, Schatzberg, Alan, Scolnick, Edward, Scott, Laura J., Sharp, Sally I., Sklar, Pamela, Smoller, Jordan W., Sobell, Janet L., Solomonson, Matthew, Stahl, Eli A., Stevens, Christine R., Suvisaari, Jaana, Tiao, Grace, Watson, Stanley J., Watts, Nicholas A., Blackwood, Douglas H., Børglum, Anders D., Cohen, Bruce M., Corvin, Aiden P., Esko, Tõnu, Freimer, Nelson B., Glatt, Stephen J., Hultman, Christina M., McQuillin, Andrew, Palotie, Aarno, Pato, Carlos N., Pato, Michele T., Pulver, Ann E., St. Clair, David, Tsuang, Ming T., Vawter, Marquis P., Walters, James T., Werge, Thomas M., Ophoff, Roel A., Sullivan, Patrick F., Owen, Michael J., Boehnke, Michael, O’Donovan, Michael C., Neale, Benjamin M., and Daly, Mark J.

Published
2022
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45. GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

Author

Mullins, Niamh, Bigdeli, Tim B, Børglum, Anders D, Coleman, Jonathan RI, Demontis, Ditte, Mehta, Divya, Power, Robert A, Ripke, Stephan, Stahl, Eli A, Starnawska, Anna, Anjorin, Adebayo, Corvin, Aiden, Sanders, Alan R, Forstner, Andreas J, Reif, Andreas, Koller, Anna C, Świątkowska, Beata, Baune, Bernhard T, Müller-Myhsok, Bertram, Penninx, Brenda WJH, Pato, Carlos, Zai, Clement, Rujescu, Dan, Hougaard, David M, Quested, Digby, Levinson, Douglas F, Binder, Elisabeth B, Byrne, Enda M, Agerbo, Esben, Streit, Fabian, Mayoral, Fermin, Bellivier, Frank, Degenhardt, Franziska, Breen, Gerome, Morken, Gunnar, Turecki, Gustavo, Rouleau, Guy A, Grabe, Hans J, Völzke, Henry, Jones, Ian, Giegling, Ina, Agartz, Ingrid, Melle, Ingrid, Lawrence, Jacob, Walters, James TR, Strohmaier, Jana, Shi, Jianxin, Hauser, Joanna, Biernacka, Joanna M, Vincent, John B, Kelsoe, John, Strauss, John S, Lissowska, Jolanta, Pimm, Jonathan, Smoller, Jordan W, Guzman-Parra, José, Berger, Klaus, Scott, Laura J, Jones, Lisa A, Azevedo, M Helena, Trzaskowski, Maciej, Kogevinas, Manolis, Rietschel, Marcella, Boks, Marco, Ising, Marcus, Grigoroiu-Serbanescu, Maria, Hamshere, Marian L, Leboyer, Marion, Frye, Mark, Nöthen, Markus M, Alda, Martin, Preisig, Martin, Nordentoft, Merete, Boehnke, Michael, O’Donovan, Michael C, Owen, Michael J, Pato, Michele T, Renteria, Miguel E, Budde, Monika, Weissman, Myrna M, Wray, Naomi R, Bass, Nicholas, Craddock, Nicholas, Smeland, Olav B, Andreassen, Ole A, Mors, Ole, Gejman, Pablo V, Sklar, Pamela, McGrath, Patrick, Hoffmann, Per, McGuffin, Peter, Lee, Phil H, Mortensen, Preben Bo, Kahn, René S, Ophoff, Roel A, Adolfsson, Rolf, Van der Auwera, Sandra, Djurovic, Srdjan, Kloiber, Stefan, and Heilmann-Heimbach, Stefanie

Subjects
Prevention, Suicide, Serious Mental Illness, Schizophrenia, Human Genome, Depression, Mental Health, Genetics, Brain Disorders, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Bipolar Disorder, Case-Control Studies, Depressive Disorder, Major, Female, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Risk Factors, Suicide, Attempted, M.R.C.Psych, Dr.Med.Sc, Dipl.-Psych, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Mood Disorders, Polygenic Risk Scoring, Psychiatric Genomics Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveMore than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.MethodsThe samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.ResultsThree genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).ConclusionsThis study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Published
2019

46. Publisher Correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection

Author

Pardiñas, Antonio F, Holmans, Peter, Pocklington, Andrew J, Escott-Price, Valentina, Ripke, Stephan, Carrera, Noa, Legge, Sophie E, Bishop, Sophie, Cameron, Darren, Hamshere, Marian L, Han, Jun, Hubbard, Leon, Lynham, Amy, Mantripragada, Kiran, Rees, Elliott, MacCabe, James H, McCarroll, Steven A, Baune, Bernhard T, Breen, Gerome, Byrne, Enda M, Dannlowski, Udo, Eley, Thalia C, Hayward, Caroline, Martin, Nicholas G, McIntosh, Andrew M, Plomin, Robert, Porteous, David J, Wray, Naomi R, Caballero, Armando, Geschwind, Daniel H, Huckins, Laura M, Ruderfer, Douglas M, Santiago, Enrique, Sklar, Pamela, Stahl, Eli A, Won, Hyejung, Agerbo, Esben, Als, Thomas D, Andreassen, Ole A, Bækvad-Hansen, Marie, Mortensen, Preben Bo, Pedersen, Carsten Bøcker, Børglum, Anders D, Bybjerg-Grauholm, Jonas, Djurovic, Srdjan, Durmishi, Naser, Pedersen, Marianne Giørtz, Golimbet, Vera, Grove, Jakob, Hougaard, David M, Mattheisen, Manuel, Molden, Espen, Mors, Ole, Nordentoft, Merete, Pejovic-Milovancevic, Milica, Sigurdsson, Engilbert, Silagadze, Teimuraz, Hansen, Christine Søholm, Stefansson, Kari, Stefansson, Hreinn, Steinberg, Stacy, Tosato, Sarah, Werge, Thomas, Collier, David A, Rujescu, Dan, Kirov, George, Owen, Michael J, O’Donovan, Michael C, and Walters, James TR

Subjects
GERAD1 Consortium, CRESTAR Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

47. Publisher Correction: Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M, Dobbyn, Amanda, Ruderfer, Douglas M, Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F, Rajagopal, Veera M, Als, Thomas D, T. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R, Purcell, Shaun, Demontis, Ditte, Børglum, Anders D, Walters, James TR, O’Donovan, Michael C, Sullivan, Patrick, Owen, Michael J, Devlin, Bernie, Sieberts, Solveig K, Cox, Nancy J, Im, Hae Kyung, Sklar, Pamela, and Stahl, Eli A

Subjects
Genetics, Neurosciences, Human Genome, Serious Mental Illness, Schizophrenia, Brain Disorders, Mental Health, Biotechnology, Mental health, CommonMind Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

In the HTML version of the article originally published, the author group 'The Schizophrenia Working Group of the Psychiatric Genomics Consortium' was displayed incorrectly. The error has been corrected in the HTML version of the article.

Published
2019

48. Population‐based identity‐by‐descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Author

Harold, Denise, Connolly, Siobhan, Riley, Brien P, Kendler, Kenneth S, McCarthy, Shane E, McCombie, William R, Richards, Alex, Owen, Michael J, O'Donovan, Michael C, Walters, James, Donnelly, Peter, Bates, Lesley, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris CA, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Hopkins, Lucinda, Pirinen, Matti, Pearson, Richard, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Waller, Matthew, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Ripke, Stephan, Neale, Benjamin M, Walters, James TR, 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 A, 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, Kimberley D, Chan, Raymond CK, and Chan, Ronald YL

Subjects
Biological Sciences, Genetics, Clinical Research, Schizophrenia, Brain Disorders, Human Genome, Prevention, Serious Mental Illness, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Adult, Case-Control Studies, Chromosome Mapping, DNA Copy Number Variations, Databases, Genetic, Exome, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Male, Middle Aged, Risk Factors, Sequence Analysis, DNA, Exome Sequencing, GWAS, IBD mapping, rare variants, Wellcome Trust Case Control Consortium 2, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Clinical Sciences, Neurosciences, Clinical sciences
Abstract

Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.

Published
2019

49. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Author

Huckins, Laura M, Dobbyn, Amanda, Ruderfer, Douglas M, Hoffman, Gabriel, Wang, Weiqing, Pardiñas, Antonio F, Rajagopal, Veera M, Als, Thomas D, T. Nguyen, Hoang, Girdhar, Kiran, Boocock, James, Roussos, Panos, Fromer, Menachem, Kramer, Robin, Domenici, Enrico, Gamazon, Eric R, Purcell, Shaun, Demontis, Ditte, Børglum, Anders D, Walters, James TR, O’Donovan, Michael C, Sullivan, Patrick, Owen, Michael J, Devlin, Bernie, Sieberts, Solveig K, Cox, Nancy J, Im, Hae Kyung, Sklar, Pamela, and Stahl, Eli A

Subjects
Biological Sciences, Genetics, Mental Health, Brain Disorders, Human Genome, Schizophrenia, 2.1 Biological and endogenous factors, Aetiology, Mental health, Brain, Case-Control Studies, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk, Transcriptome, CommonMind Consortium, Schizophrenia Working Group of the Psychiatric Genomics Consortium, iPSYCH-GEMS Schizophrenia Working Group, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

Published
2019

50. Integrative functional genomic analysis of human brain development and neuropsychiatric risks

Author

Li, Mingfeng, Santpere, Gabriel, Imamura Kawasawa, Yuka, Evgrafov, Oleg V, Gulden, Forrest O, Pochareddy, Sirisha, Sunkin, Susan M, Li, Zhen, Shin, Yurae, Zhu, Ying, Sousa, André MM, Werling, Donna M, Kitchen, Robert R, Kang, Hyo Jung, Pletikos, Mihovil, Choi, Jinmyung, Muchnik, Sydney, Xu, Xuming, Wang, Daifeng, Lorente-Galdos, Belen, Liu, Shuang, Giusti-Rodríguez, Paola, Won, Hyejung, de Leeuw, Christiaan A, Pardiñas, Antonio F, Hu, Ming, Jin, Fulai, Li, Yun, Owen, Michael J, O’Donovan, Michael C, Walters, James TR, Posthuma, Danielle, Reimers, Mark A, Levitt, Pat, Weinberger, Daniel R, Hyde, Thomas M, Kleinman, Joel E, Geschwind, Daniel H, Hawrylycz, Michael J, State, Matthew W, Sanders, Stephan J, Sullivan, Patrick F, Gerstein, Mark B, Lein, Ed S, Knowles, James A, Sestan, Nenad, Willsey, A Jeremy, Oldre, Aaron, Szafer, Aaron, Camarena, Adrian, Cherskov, Adriana, Charney, Alexander W, Abyzov, Alexej, Kozlenkov, Alexey, Safi, Alexias, Jones, Allan R, Ashley-Koch, Allison E, Ebbert, Amanda, Price, Amanda J, Sekijima, Amanda, Kefi, Amira, Bernard, Amy, Amiri, Anahita, Sboner, Andrea, Clark, Andrew, Jaffe, Andrew E, Tebbenkamp, Andrew TN, Sodt, Andy J, Guillozet-Bongaarts, Angie L, Nairn, Angus C, Carey, Anita, Huttner, Anita, Chervenak, Ann, Szekely, Anna, Shieh, Annie W, Harmanci, Arif, Lipska, Barbara K, Carlyle, Becky C, Gregor, Ben W, Kassim, Bibi S, Sheppard, Brooke, Bichsel, Candace, Hahn, Chang-Gyu, Lee, Chang-Kyu, Chen, Chao, Kuan, Chihchau L, Dang, Chinh, Lau, Chris, Cuhaciyan, Christine, Armoskus, Christoper, Mason, Christopher E, Liu, Chunyu, Slaughterbeck, Cliff R, Bennet, Crissa, Pinto, Dalila, Polioudakis, Damon, Franjic, Daniel, Miller, Daniel J, Bertagnolli, Darren, and Lewis, David A

Subjects
Human Genome, Genetics, Neurosciences, Biotechnology, Pediatric, Mental Health, Brain, Epigenesis, Genetic, Epigenomics, Gene Expression Regulation, Developmental, Gene Regulatory Networks, Humans, Mental Disorders, Nervous System Diseases, Neurogenesis, Single-Cell Analysis, Transcriptome, BrainSpan Consortium, PsychENCODE Consortium, PsychENCODE Developmental Subgroup, General Science & Technology
Abstract

To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.

Published
2018

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