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2. Convergent coexpression of autism-associated genes suggests some novel risk genes may not be detectable in large-scale genetic studies

Author

Liao, Calwing, Moyses-Oliveira, Mariana, De Esch, Celine E.F., Bhavsar, Riya, Nuttle, Xander, Li, Aiqun, Yu, Alex, Burt, Nicholas D., Erdin, Serkan, Fu, Jack M., Wang, Minghui, Morley, Theodore, Han, Lide, Dion, Patrick A., Rouleau, Guy A., Zhang, Bin, Brennand, Kristen J., Talkowski, Michael E., and Ruderfer, Douglas M.

Published
2023
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3. Copy-number variants in the contactin-5 gene are a potential risk factor for autism spectrum disorder

Author

Schmilovich, Zoe, Huguet, Guillaume, He, Qin, Musa-Johnson, Amélie, Douard, Elise, Loum, Mor Absa, Liao, Calwing, Ross, Jay P., Dionne-Laporte, Alexandre, Spiegelman, Dan, Jean-Louis, Martineau, Saci, Zohra, Hayward, Caroline, Banaschewski, Tobias, Bokde, Arun, Desrivieres, Sylvane, Lemaitre, Herve, Schumann, Gunter, Xiong, Lan, Dion, Patrick A., Jacquemont, Sébastien, Chaumette, Boris, and Rouleau, Guy A.

Published
2022
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7. Chronic lithium treatment alters the excitatory/ inhibitory balance of synaptic networks and reduces mGluR5-PKC signalling in mouse cortical neurons

Author

Khayachi, Anouar, Ase, Ariel, Liao, Calwing, Kamesh, Anusha, Kuhlmann, Naila, Schorova, Lenka, Chaumette, Boris, Dion, Patrick, Alda, Martin, Seguela, Philippe, Rouleau, Guy, and Milnerwood, Austen

Subjects
Lithium -- Dosage and administration -- Patient outcomes, Neural circuitry -- Physiological aspects, Synapses -- Physiological aspects, Cellular signal transduction -- Health aspects, Health, Psychology and mental health
Abstract

Background: Bipolar disorder is characterized by cyclical alternation between mania and depression, often comorbid with psychosis and suicide. Compared with other medications, the mood stabilizer lithium is the most effective treatment for the prevention of manic and depressive episodes. However, the pathophysiology of bipolar disorder and lithium's mode of action are yet to be fully understood. Evidence suggests a change in the balance of excitatory and inhibitory activity, favouring excitation in bipolar disorder. In the present study, we sought to establish a holistic understanding of the neuronal consequences of lithium exposure in mouse cortical neurons, and to identify underlying mechanisms of action. Methods: We used a range of technical approaches to determine the effects of acute and chronic lithium treatment on mature mouse cortical neurons. We combined RNA screening and biochemical and electrophysiological approaches with confocal immunofluorescence and live-cell calcium imaging. Results: We found that only chronic lithium treatment significantly reduced intracellular calcium flux, specifically by activating metabotropic glutamatergic receptor 5. This was associated with altered phosphorylation of protein kinase C and glycogen synthase kinase 3, reduced neuronal excitability and several alterations to synapse function. Consequently, lithium treatment shifts the excitatory-inhibitory balance toward inhibition. Limitations: The mechanisms we identified should be validated in future by similar experiments in whole animals and human neurons. Conclusion: Together, the results revealed how lithium dampens neuronal excitability and the activity of the glutamatergic network, both of which are predicted to be overactive in the manic phase of bipolar disorder. Our working model of lithium action enables the development of targeted strategies to restore the balance of overactive networks, mimicking the therapeutic benefits of lithium but with reduced toxicity., Introduction Bipolar disorder is a major psychiatric illness that affects 1% to 3% of the population worldwide, and it is 1 of the top 10 causes of disability. (1,2) Bipolar [...]

Published
2021
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8. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Mullins, Niamh, Forstner, Andreas J., O’Connell, Kevin S., Coombes, Brandon, Coleman, Jonathan R. I., Qiao, Zhen, Als, Thomas D., Bigdeli, Tim B., Børte, Sigrid, Bryois, Julien, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Steinberg, Stacy, Trubetskoy, Vassily, Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Agerbo, Esben, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bækvad-Hansen, Marie, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøcker Pedersen, Carsten, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Bybjerg-Grauholm, Jonas, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Clarke, Toni-Kim, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Degenhardt, Franziska, Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Giørtz Pedersen, Marianne, Gizer, Ian R., Gordon, Scott D., Gordon-Smith, Katherine, Greenwood, Tiffany A., Grove, Jakob, Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Herms, Stefan, Hoffmann, Per, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Knowles, James A., Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lucae, Susanne, Lundberg, Martin, MacIntyre, Donald J., Magnusson, Sigurdur H., Maier, Wolfgang, Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, Mattheisen, Manuel, McCarroll, Steven A., McGregor, Nathaniel W., McGuffin, Peter, McKay, James D., Medeiros, Helena, Medland, Sarah E., Millischer, Vincent, Montgomery, Grant W., Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O’Brien, Niamh, O’Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Potash, James B., Quested, Digby, Raj, Towfique, Rapaport, Mark H., DePaulo, J. Raymond, Regeer, Eline J., Rice, John P., Rivas, Fabio, Rivera, Margarita, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Schulte, Eva C., Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sigurdsson, Engilbert, Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Smith, Daniel J., Sobell, Janet L., Søholm Hansen, Christine, Soler Artigas, Maria, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Thorgeirsson, Thorgeir E., Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Witt, Stephanie H., Xi, Simon, Xu, Wei, Yang, Jessica Mei Kay, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Børglum, Anders D., Breen, Gerome, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dannlowski, Udo, Dikeos, Dimitris, Esko, Tõnu, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Goes, Fernando S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hougaard, David M., Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Jones, Ian, Jones, Lisa A., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lewis, Cathryn M., Li, Qingqin S., Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Martin, Nicholas G., Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Milani, Lili, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Mowry, Bryan, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Nordentoft, Merete, Nöthen, Markus M., O’Donovan, Michael C., Oedegaard, Ketil J., Olsson, Tomas, Owen, Michael J., Paciga, Sara A., Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Perlis, Roy H., Posthuma, Danielle, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rietschel, Marcella, Ripke, Stephan, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Shannon Weickert, Cynthia, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Streit, Fabian, Sullivan, Patrick F., Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Werge, Thomas, Wray, Naomi R., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Cichon, Sven, Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., and Andreassen, Ole A.

Published
2021
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13. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Author

Demontis, Ditte, Walters, G. Bragi, Athanasiadis, Georgios, Walters, Raymond, Therrien, Karen, Nielsen, Trine Tollerup, Farajzadeh, Leila, Voloudakis, Georgios, Bendl, Jaroslav, Zeng, Biau, Zhang, Wen, Grove, Jakob, Als, Thomas D., Duan, Jinjie, Satterstrom, F. Kyle, Bybjerg-Grauholm, Jonas, Bækved-Hansen, Marie, Gudmundsson, Olafur O., Magnusson, Sigurdur H., Baldursson, Gisli, Davidsdottir, Katrin, Haraldsdottir, Gyda S., Agerbo, Esben, Hoffman, Gabriel E., Dalsgaard, Søren, Martin, Joanna, Ribasés, Marta, Boomsma, Dorret I., Soler Artigas, Maria, Roth Mota, Nina, Howrigan, Daniel, Medland, Sarah E., Zayats, Tetyana, Rajagopal, Veera M., Havdahl, Alexandra, Doyle, Alysa, Reif, Andreas, Thapar, Anita, Cormand, Bru, Liao, Calwing, Burton, Christie, Bau, Claiton H. D., Rovaris, Diego Luiz, Sonuga-Barke, Edmund, Corfield, Elizabeth, Grevet, Eugenio Horacio, Larsson, Henrik, Gizer, Ian R., Waldman, Irwin, Brikell, Isabell, Haavik, Jan, Crosbie, Jennifer, McGough, James, Kuntsi, Jonna, Glessner, Joseph, Langley, Kate, Lesch, Klaus-Peter, Rohde, Luis Augusto, Hutz, Mara H., Klein, Marieke, Bellgrove, Mark, Tesli, Martin, O’Donovan, Michael C., Andreassen, Ole Andreas, Leung, Patrick W. L., Pan, Pedro M., Joober, Ridha, Schachar, Russel, Loo, Sandra, Witt, Stephanie H., Reichborn-Kjennerud, Ted, Banaschewski, Tobias, Hawi, Ziarih, Daly, Mark J., Mors, Ole, Nordentoft, Merete, Hougaard, David M., Mortensen, Preben Bo, Faraone, Stephen V., Stefansson, Hreinn, Roussos, Panos, Franke, Barbara, Werge, Thomas, Neale, Benjamin M., Stefansson, Kari, Børglum, Anders D., APH - Methodology, APH - Mental Health, Amsterdam Reproduction & Development, and Biological Psychology

Subjects
Cognition, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], SDG 3 - Good Health and Well-being, Genetics, Brain, Humans, Genetic Predisposition to Disease, Attention Deficit Disorder with Hyperactivity/genetics, Genome-Wide Association Study
Abstract

Contains fulltext : 290804.pdf (Publisher’s version ) (Closed access) Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention. 01 februari 2023

Published
2023

18. Association of Essential Tremor With Novel Risk Loci

Author

Liao, Calwing, Castonguay, Charles-Etienne, Heilbron, Karl, Vuokila, Veikko, Medeiros, Miranda, Houle, Gabrielle, Akçimen, Fulya, Ross, Jay P., Catoire, Helene, Diez-Fairen, Monica, Kang, Jooeun, Mueller, Stefanie H., Girard, Simon L., Hopfner, Franziska, Lorenz, Delia, Clark, Lorraine N., Soto-Beasley, Alexandra I., Klebe, Stephan, Hallett, Mark, Wszolek, Zbigniew K., Pendziwiat, Manuela, Lorenzo-Betancor, Oswaldo, Seppi, Klaus, Berg, Daniela, Vilariño-Güell, Carles, Postuma, Ronald B., Bernard, Geneviève, Dupré, Nicolas, Jankovic, Joseph, Testa, Claudia M., Ross, Owen A., Arzberger, Thomas, Chouinard, Sylvain, Louis, Elan D., Mandich, Paola, Vitale, Carmine, Barone, Paolo, García-Martín, Elena, Alonso-Navarro, Hortensia, Agúndez, José A. G., Jiménez-Jiménez, Félix Javier, Pastor, Pau, Rajput, Alex, Deuschl, Günther, Kuhlenbaümer, Gregor, Meijer, Inge A., Dion, Patrick A., and Rouleau, Guy A.

Subjects
Research, Online First, Comments, Original Investigation
Abstract

Key Points Question Can common genetic variants associated with essential tremor (ET) be identified? Findings In this genome-wide association study and meta-analysis including genetic data on 483 054 individuals, 5 genome-wide significant loci were associated with risk of ET and common variants were associated with approximately 18% of ET heritability. Meaning Findings of this study may help identify new genes and inform ET biology., This genome-wide association study identifies common variants associated with risk of essential tremor., Importance Essential tremor (ET) is one of the most common movement disorders, affecting 5% of the general population older than 65 years. Common variants are thought to contribute toward susceptibility to ET, but no variants have been robustly identified. Objective To identify common genetic factors associated with risk of ET. Design, Setting, and Participants Case-control genome-wide association study. Inverse-variance meta-analysis was used to combine cohorts. Multicenter samples collected from European populations were collected from January 2010 to September 2019 as part of an ongoing study. Included patients were clinically diagnosed with or reported having ET. Control individuals were not diagnosed with or reported to have ET. Of 485 250 individuals, data for 483 054 passed data quality control and were used. Main Outcomes and Measures Genotypes of common variants associated with risk of ET. Results Of the 483 054 individuals included, there were 7177 with ET (3693 [51.46%] female; mean [SD] age, 62.66 [15.12] years), and 475 877 control individuals (253 785 [53.33%] female; mean [SD] age, 56.40 [17.6] years). Five independent genome-wide significant loci and were identified and were associated with approximately 18% of ET heritability. Functional analyses found significant enrichment in the cerebellar hemisphere, cerebellum, and axonogenesis pathways. Genetic correlation (r), which measures the degree of genetic overlap, revealed significant common variant overlap with Parkinson disease (r, 0.28; P = 2.38 × 10−8) and depression (r, 0.12; P = 9.78 × 10−4). A separate fine-mapping of transcriptome-wide association hits identified genes such as BACE2, LRRN2, DHRS13, and LINC00323 in disease-relevant brain regions, such as the cerebellum. Conclusions and Relevance The results of this genome-wide association study suggest that a portion of ET heritability can be explained by common genetic variation and can help identify new common genetic risk factors for ET.

Published
2022

19. Influence of polygenic risk scores for schizophrenia and resilience on the cognition of individuals at-risk for psychosis

Author

He, Qin, Jantac Mam-Lam-Fook, Célia, Chaignaud, Julie, Danset-Alexandre, Charlotte, Iftimovici, Anton, Gradels Hauguel, Johanna, Houle, Gabrielle, Liao, Calwing, Amado, Isabelle, Bourgin, Julie, Daban-Huard, Claire, Magaud, Emilie, Plaze, Marion, Rivollier, Fabrice, Dion, Patrick, Rouleau, Guy, Kebir, Oussama, Krebs, Marie-Odile, Chaumette, Boris, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and ANR-17-CE37-0003,EPI_young,Dysrégulation de l'épigenome en lien avec l'usage de substances et santé mentale des jeunes(2017)

Subjects
Psychosis, Trail Making Test, Neurosciences. Biological psychiatry. Neuropsychiatry, Neuropsychological Tests, behavioral disciplines and activities, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cognition, Wisconsin Card Sorting Test, Risk Factors, mental disorders, medicine, Verbal fluency test, Humans, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, Intelligence quotient, Comparative genomics, Wechsler Adult Intelligence Scale, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, sense organs, Psychology, Neurocognitive, 030217 neurology & neurosurgery, RC321-571, Clinical psychology
Abstract

Cognitive impairment is a core feature of schizophrenia which precedes the onset of full psychotic symptoms, even in the ultra-high-risk stage (UHR). Polygenic risk scores (PRS) can be computed for many psychiatric disorders and phenotyping traits, including scores for resilience. We explored the correlations between several PRS and neurocognition in UHR individuals. We included 107 UHR individuals; 29.9% of them converted to psychosis (UHR-C) while 57.0% did not (UHR-NC) during the 1-year follow-up. Cognitive performances were assessed with the Wechsler Adult Intelligence Scale estimating the Intelligence Quotient (IQ), the Trail Making Test, the verbal fluency, the Stroop test, and the Wisconsin card sorting test. Linear regression models were used to test their association with the PRS for schizophrenia, bipolar disorder, major depression, ADHD, cross-disorders, cognitive performance, intelligence, education attainment, and resilience to schizophrenia. UHR-C had a lower IQ than UHR-NC. The PRS for schizophrenia negatively correlated with IQ, while the PRS for cognitive performance and for resilience positively correlated with IQ. PRS for schizophrenia showed a significant correlation with working memory and processing speed indices. PRS for schizophrenia showed a higher effect on IQ in UHR-NC, and UHR-NC with high PRS for schizophrenia had a similar IQ as UHR-C. Conversely, UHR-C with a high PRS for resilience performed as well as UHR-NC. Our findings suggest that cognitive deficits may predate the onset of psychosis. The genetic architecture of schizophrenia seems to impacts the cognition in UHR-NC. Cognition is also mediated by PRS for resilience.

Published
2021

20. Copy-Number Variants in The Contactin-5 Gene Are a Potential Risk Factor for Autism Spectrum Disorder

Author

Schmilovich, Zoe, primary, Huguet, Guillaume, additional, He, Qin, additional, Musa-Johnson, Amélie, additional, Douard, Elise, additional, Loum, Mor Absa, additional, Liao, Calwing, additional, Ross, Jay P., additional, Dionne-Laporte, Alexandre, additional, Spiegelman, Dan, additional, Hayward, Caroline, additional, Banaschewski, Tobias, additional, Bokde, Arun, additional, Desrivieres, Sylvane, additional, Lemaitre, Herve, additional, Schumann, Gunter, additional, Xiong, Lan, additional, Dion, Patrick A., additional, Jacquemont, Sébastien, additional, Chaumette, Boris, additional, and Rouleau, Guy A., additional

Published
2021
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21. Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder (Nature Communications, (2021), 12, 1, (576), 10.1038/s41467-020-20443-2)

Author

Demontis, Ditte, Walters, Raymond K., Rajagopal, Veera M., Waldman, Irwin D., Grove, Jakob, Als, Thomas D., Dalsgaard, Søren, Ribasés, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, Andreassen, Ole A., Arranz, Maria Jesús, Banaschewski, Tobias, Bau, Claiton, Bellgrove, Mark, Biederman, Joseph, Brikell, Isabell, Buitelaar, Jan K., Burton, Christie L., Casas, Miguel, Crosbie, Jennifer, Doyle, Alysa E., Ebstein, Richard P., Elia, Josephine, Elizabeth, Corfield C., Grevet, Eugenio, Grizenko, Natalie, Havdahl, Alexandra, Hawi, Ziarih, Hebebrand, Johannes, Hervas, Amaia, Hohmann, Sarah, Haavik, Jan, Joober, Ridha, Kent, Lindsey, Kuntsi, Jonna, Langley, Kate, Larsson, Henrik, Lesch, Klaus-Peter, Leung, Patrick W. L., Liao, Calwing, Loo, Sandra K., Martin, Joanna, Martin, Nicholas G., Medland, Sarah E., Miranda, Ana, Mota, Nina Roth, Oades, Robert D., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Rietschel, Marcella, Roeyers, Herbert, Rohde, Luis Augusto, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Schachar, Russell James, Sengupta, Sarojini, Artigas, Maria Soler, Steinhausen, Hans-Christoph, Thapar, Anita, Witt, Stephanie H., Yang, Li, Zayats, Tetyana, Zhang-James, Yanli, Cormand, Bru, Hougaard, David M., Neale, Benjamin M., Franke, Barbara, Faraone, Stephen V., and Børglum, Anders D.

Subjects
Medizin
Abstract

The original version of this Article contained an error in the spelling of the author Marta Ribasés, which was incorrectly given as Marta Ribasas. This has now been corrected in both the PDF and HTML versions of the Article. CA extern, Korrektur zu: 10.1038/s41467-020-20443-2

Published
2021

22. Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Author

Demontis, Ditte, Walters, Raymond K., Rajagopal, Veera M., Waldman, Irwin D., Grove, Jakob, Als, Thomas D., Dalsgaard, Søren, Ribasas, Marta, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Maria, Werge, Thomas, Nordentoft, Merete, Mors, Ole, Mortensen, Preben Bo, (PGC), ADHD Working Group of the Psychiatric Genomics Consortium, Andreassen, Ole A., Arranz, Maria Jesús, Banaschewski, Tobias, Bau, Claiton, Bellgrove, Mark, Biederman, Joseph, Brikell, Isabell, Buitelaar, Jan K., Burton, Christie L., Casas, Miguel, Crosbie, Jennifer, Doyle, Alysa E., Ebstein, Richard P., Elia, Josephine, Elizabeth, Corfield C., Grevet, Eugenio, Grizenko, Natalie, Havdahl, Alexandra, Hawi, Ziarih, Hebebrand, Johannes, Hervas, Amaia, Hohmann, Sarah, Haavik, Jan, Joober, Ridha, Kent, Lindsey, Kuntsi, Jonna, Langley, Kate, Larsson, Henrik, Lesch, Klaus-Peter, Leung, Patrick W. L., Liao, Calwing, Loo, Sandra K., Martin, Joanna, Martin, Nicholas G., Medland, Sarah E., Miranda, Ana, Mota, Nina Roth, Oades, Robert D., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Rietschel, Marcella, Roeyers, Herbert, Rohde, Luis Augusto, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Schachar, Russell James, Sengupta, Sarojini, Artigas, Maria Soler, Steinhausen, Hans-Christoph, Thapar, Anita, Witt, Stephanie H., Yang, Li, Zayats, Tetyana, Zhang-James, Yanli, Cormand, Bru, Hougaard, David M., Neale, Benjamin M., Franke, Barbara, Faraone, Stephen V., Børglum, Anders D., University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, University of St Andrews. Cellular Medicine Division, Institut Català de la Salut, [Demontis D, Rajagopal VM, Als TD] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. Center for Genomics and Personalized Medicine, Aarhus, Denmark. Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. [Walters RK] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [Waldman ID] Department of Psychology, Emory University, Atlanta, GA, USA. [Grove J] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark. Center for Genomics and Personalized Medicine, Aarhus, Denmark. Department of Biomedicine - Human Genetics, Aarhus University, Aarhus, Denmark. [Ribasés M] Unitat de Psiquiatria Genètica, Grup de recerca en Psiquiatria, salut mental i addiccions, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Psiquiatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Biomedical Network Research Center on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Departament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Barcelona, Catalonia, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, 0301 basic medicine, Multifactorial Inheritance, Trastorns per dèficit d'atenció amb hiperactivitat en els infants, Medizin, General Physics and Astronomy, Genome-wide association study, Comorbidity, Genome-wide association studies, Attention deficit disorder with hyperactivity in children, conducta y mecanismos de la conducta::conducta::conducta y mecanismos de la conducta::conducta::conducta infantil::conducta problemática [PSIQUIATRÍA Y PSICOLOGÍA], Cohort Studies, 0302 clinical medicine, Mental Disorders::Neurodevelopmental Disorders::Attention Deficit and Disruptive Behavior Disorders::Attention Deficit Disorder with Hyperactivity [PSYCHIATRY AND PSYCHOLOGY], Risk Factors, 2.1 Biological and endogenous factors, Medicine, Attention Deficit Disorder with Hyperactivity/epidemiology, Aetiology, Child, China/epidemiology, Violence Research, Pediatric, Multidisciplinary, Genetic Predisposition to Disease/genetics, Attention Deficit and Disruptive Behavior Disorders/epidemiology, Single Nucleotide, 3. Good health, Europe, Mental Health, Attention Deficit and Disruptive Behavior Disorders, Cohort, Genome-Wide Association Study/methods, Attention Deficit Disorder (ADD), Female, medicine.symptom, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Clinical psychology, China, Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Science, Context (language use), Locus (genetics), QH426 Genetics, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, General Biochemistry, Genetics and Molecular Biology, Europe/epidemiology, 03 medical and health sciences, Aggressiveness in children, Behavioral and Social Science, mental disorders, Genetics, ADHD, Humans, SNP, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, Polymorphism, Author Correction, QH426, Multifactorial Inheritance/genetics, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Aggression, Prevention, Human Genome, DAS, General Chemistry, Agressivitat en els infants, Heritability, medicine.disease, Attention Deficit Hyperactivity Disorder (ADHD), Behavior and Behavior Mechanisms::Behavior::Behavior and Behavior Mechanisms::Behavior::Child Behavior::Problem Behavior [PSYCHIATRY AND PSYCHOLOGY], Brain Disorders, Genòmica, ADHD Working Group of the Psychiatric Genomics Consortium, Trastorn per dèficit d'atenció amb hiperactivitat, 030104 developmental biology, Attention Deficit Disorder with Hyperactivity, técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], RC0321, trastornos mentales::trastornos del desarrollo neurológico::trastornos conductuales disruptivos y déficit de atención::trastornos de déficit de atención con hiperactividad [PSIQUIATRÍA Y PSICOLOGÍA], business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior., ADHD is often found to be comorbid with disruptive behavior disorders, but the genetic loci underlying this comorbidity are unknown. Here, the authors have performed a GWAS meta-analysis of ADHD with disruptive behavior disorders, finding three genome-wide significant loci in Europeans, and replicating one in a Chinese cohort.

Published
2021

23. Chronic lithium treatment alters the excitatory/inhibitory balance of synaptic networks and reduces mGluR5–PKC signalling in mouse cortical neurons

Author

Khayachi, Anouar, primary, Ase, Ariel, additional, Liao, Calwing, additional, Kamesh, Anusha, additional, Kuhlmann, Naila, additional, Schorova, Lenka, additional, Chaumette, Boris, additional, Dion, Patrick, additional, Alda, Martin, additional, Séguéla, Philippe, additional, Rouleau, Guy, additional, and Milnerwood, Austen, additional

Published
2021
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24. Genome-Wide Association Study Meta-Analysis for Parkinson Disease Motor Subtypes

Author

Alfradique-Dunham, Isabel, primary, Al-Ouran, Rami, additional, von Coelln, Rainer, additional, Blauwendraat, Cornelis, additional, Hill, Emily, additional, Luo, Lan, additional, Stillwell, Amanda, additional, Young, Emily, additional, Kaw, Anita, additional, Tan, Manuela, additional, Liao, Calwing, additional, Hernandez, Dena, additional, Pihlstrom, Lasse, additional, Grosset, Donald, additional, Shulman, Lisa M., additional, Liu, Zhandong, additional, Rouleau, Guy A., additional, Nalls, Mike, additional, Singleton, Andrew B., additional, Morris, Huw, additional, Jankovic, Joseph, additional, and Shulman, Joshua M., additional

Published
2021
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25. Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Author

Akçimen, Fulya, Martins, Sandra, Liao, Calwing, Bourassa, Cynthia V., Catoire, Hélène, Nicholson, Garth A., Riess, Olaf, Raposo, Mafalda, França Júnior, Marcondes Cavalcante, Vasconcelos, João, Lima, Manuela, Lopes-Cendes, Iscia Teresinha, Pereira, Maria Luiza Saraiva, Jardim, Laura Bannach, Sequeiros, Jorge, Dion, Patrick A., and Rouleau, Guy A.

Subjects
Doença de Machado-Joseph, Machado-Joseph disease, Idade de início, GWAS, Age at onset, ATXN3, Modifier, Loci gênicos, Estudo de associação genômica ampla
Abstract

Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study (Pearson’s correlation coefficient R2 = 0.62). Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10−5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.

Published
2020

27. Assessing the NOTCH2NLC GGC expansion in European patients with essential tremor

Author

Liao, Calwing, primary, Akçimen, Fulya, additional, Diez-Fairen, Monica, additional, Houle, Gabrielle, additional, Ross, Jay P, additional, Schmilovich, Zoe, additional, Spiegelman, Dan, additional, Vuokila, Veikko, additional, Catoire, Hélène, additional, Meijer, Inge A, additional, Pastor, Pau, additional, Rajput, Alex, additional, Dion, Patrick A, additional, and Rouleau, Guy A, additional

Published
2020
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29. Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Mullins, Niamh, primary, Forstner, Andreas J., additional, O’Connell, Kevin S., additional, Coombes, Brandon, additional, Coleman, Jonathan R. I., additional, Qiao, Zhen, additional, Als, Thomas D., additional, Bigdeli, Tim B., additional, Børte, Sigrid, additional, Bryois, Julien, additional, Charney, Alexander W., additional, Drange, Ole Kristian, additional, Gandal, Michael J., additional, Hagenaars, Saskia P., additional, Ikeda, Masashi, additional, Kamitaki, Nolan, additional, Kim, Minsoo, additional, Krebs, Kristi, additional, Panagiotaropoulou, Georgia, additional, Schilder, Brian M., additional, Sloofman, Laura G., additional, Steinberg, Stacy, additional, Trubetskoy, Vassily, additional, Winsvold, Bendik S., additional, Won, Hong-Hee, additional, Abramova, Liliya, additional, Adorjan, Kristina, additional, Agerbo, Esben, additional, Al Eissa, Mariam, additional, Albani, Diego, additional, Alliey-Rodriguez, Ney, additional, Anjorin, Adebayo, additional, Antilla, Verneri, additional, Antoniou, Anastasia, additional, Awasthi, Swapnil, additional, Baek, Ji Hyun, additional, Bækvad-Hansen, Marie, additional, Bass, Nicholas, additional, Bauer, Michael, additional, Beins, Eva C., additional, Bergen, Sarah E., additional, Birner, Armin, additional, Bøcker Pedersen, Carsten, additional, Bøen, Erlend, additional, Boks, Marco P., additional, Bosch, Rosa, additional, Brum, Murielle, additional, Brumpton, Ben M., additional, Brunkhorst-Kanaan, Nathalie, additional, Budde, Monika, additional, Bybjerg-Grauholm, Jonas, additional, Byerley, William, additional, Cairns, Murray, additional, Casas, Miquel, additional, Cervantes, Pablo, additional, Clarke, Toni-Kim, additional, Cruceanu, Cristiana, additional, Cuellar-Barboza, Alfredo, additional, Cunningham, Julie, additional, Curtis, David, additional, Czerski, Piotr M., additional, Dale, Anders M., additional, Dalkner, Nina, additional, David, Friederike S., additional, Degenhardt, Franziska, additional, Djurovic, Srdjan, additional, Dobbyn, Amanda L., additional, Douzenis, Athanassios, additional, Elvsåshagen, Torbjørn, additional, Escott-Price, Valentina, additional, Ferrier, I. Nicol, additional, Fiorentino, Alessia, additional, Foroud, Tatiana M., additional, Forty, Liz, additional, Frank, Josef, additional, Frei, Oleksandr, additional, Freimer, Nelson B., additional, Frisén, Louise, additional, Gade, Katrin, additional, Garnham, Julie, additional, Gelernter, Joel, additional, Giørtz Pedersen, Marianne, additional, Gizer, Ian R., additional, Gordon, Scott D., additional, Gordon-Smith, Katherine, additional, Greenwood, Tiffany A., additional, Grove, Jakob, additional, Guzman-Parra, José, additional, Ha, Kyooseob, additional, Haraldsson, Magnus, additional, Hautzinger, Martin, additional, Heilbronner, Urs, additional, Hellgren, Dennis, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Holmans, Peter A., additional, Huckins, Laura, additional, Jamain, Stéphane, additional, Johnson, Jessica S., additional, Kalman, Janos L., additional, Kamatani, Yoichiro, additional, Kennedy, James L., additional, Kittel-Schneider, Sarah, additional, Knowles, James A., additional, Kogevinas, Manolis, additional, Koromina, Maria, additional, Kranz, Thorsten M., additional, Kranzler, Henry R., additional, Kubo, Michiaki, additional, Kupka, Ralph, additional, Kushner, Steven A., additional, Lavebratt, Catharina, additional, Lawrence, Jacob, additional, Leber, Markus, additional, Lee, Heon-Jeong, additional, Lee, Phil H., additional, Levy, Shawn E., additional, Lewis, Catrin, additional, Liao, Calwing, additional, Lucae, Susanne, additional, Lundberg, Martin, additional, MacIntyre, Donald J., additional, Magnusson, Sigurdur H., additional, Maier, Wolfgang, additional, Maihofer, Adam, additional, Malaspina, Dolores, additional, Maratou, Eirini, additional, Martinsson, Lina, additional, Mattheisen, Manuel, additional, McCarroll, Steven A., additional, McGregor, Nathaniel W., additional, McGuffin, Peter, additional, McKay, James D., additional, Medeiros, Helena, additional, Medland, Sarah E., additional, Millischer, Vincent, additional, Montgomery, Grant W., additional, Moran, Jennifer L., additional, Morris, Derek W., additional, Mühleisen, Thomas W., additional, O’Brien, Niamh, additional, O’Donovan, Claire, additional, Loohuis, Loes M. Olde, additional, Oruc, Lilijana, additional, Papiol, Sergi, additional, Pardiñas, Antonio F., additional, Perry, Amy, additional, Pfennig, Andrea, additional, Porichi, Evgenia, additional, Potash, James B., additional, Quested, Digby, additional, Raj, Towfique, additional, Rapaport, Mark H., additional, DePaulo, J. Raymond, additional, Regeer, Eline J., additional, Rice, John P., additional, Rivas, Fabio, additional, Rivera, Margarita, additional, Roth, Julian, additional, Roussos, Panos, additional, Ruderfer, Douglas M., additional, Sánchez-Mora, Cristina, additional, Schulte, Eva C., additional, Senner, Fanny, additional, Sharp, Sally, additional, Shilling, Paul D., additional, Sigurdsson, Engilbert, additional, Sirignano, Lea, additional, Slaney, Claire, additional, Smeland, Olav B., additional, Smith, Daniel J., additional, Sobell, Janet L., additional, Søholm Hansen, Christine, additional, Artigas, Maria Soler, additional, Spijker, Anne T., additional, Stein, Dan J., additional, Strauss, John S., additional, Świątkowska, Beata, additional, Terao, Chikashi, additional, Thorgeirsson, Thorgeir E., additional, Toma, Claudio, additional, Tooney, Paul, additional, Tsermpini, Evangelia-Eirini, additional, Vawter, Marquis P., additional, Vedder, Helmut, additional, Walters, James T. R., additional, Witt, Stephanie H., additional, Xi, Simon, additional, Xu, Wei, additional, Yang, Jessica Mei Kay, additional, Young, Allan H., additional, Young, Hannah, additional, Zandi, Peter P., additional, Zhou, Hang, additional, Zillich, Lea, additional, Psychiatry, HUNT All-In, additional, Adolfsson, Rolf, additional, Agartz, Ingrid, additional, Alda, Martin, additional, Alfredsson, Lars, additional, Babadjanova, Gulja, additional, Backlund, Lena, additional, Baune, Bernhard T., additional, Bellivier, Frank, additional, Bengesser, Susanne, additional, Berrettini, Wade H., additional, Blackwood, Douglas H. R., additional, Boehnke, Michael, additional, Børglum, Anders D., additional, Breen, Gerome, additional, Carr, Vaughan J., additional, Catts, Stanley, additional, Corvin, Aiden, additional, Craddock, Nicholas, additional, Dannlowski, Udo, additional, Dikeos, Dimitris, additional, Esko, Tõnu, additional, Etain, Bruno, additional, Ferentinos, Panagiotis, additional, Frye, Mark, additional, Fullerton, Janice M., additional, Gawlik, Micha, additional, Gershon, Elliot S., additional, Goes, Fernando S., additional, Green, Melissa J., additional, Grigoroiu-Serbanescu, Maria, additional, Hauser, Joanna, additional, Henskens, Frans, additional, Hillert, Jan, additional, Hong, Kyung Sue, additional, Hougaard, David M., additional, Hultman, Christina M., additional, Hveem, Kristian, additional, Iwata, Nakao, additional, Jablensky, Assen V., additional, Jones, Ian, additional, Jones, Lisa A., additional, S. Kahn, René, additional, Kelsoe, John R., additional, Kirov, George, additional, Landén, Mikael, additional, Leboyer, Marion, additional, Lewis, Cathryn M., additional, Li, Qingqin S., additional, Lissowska, Jolanta, additional, Lochner, Christine, additional, Loughland, Carmel, additional, Martin, Nicholas G., additional, Mathews, Carol A., additional, Mayoral, Fermin, additional, McElroy, Susan L., additional, McIntosh, Andrew M., additional, McMahon, Francis J., additional, Melle, Ingrid, additional, Michie, Patricia, additional, Milani, Lili, additional, Mitchell, Philip B., additional, Morken, Gunnar, additional, Mors, Ole, additional, Mortensen, Preben Bo, additional, Mowry, Bryan, additional, Müller-Myhsok, Bertram, additional, Myers, Richard M., additional, Neale, Benjamin M., additional, Nievergelt, Caroline M., additional, Nordentoft, Merete, additional, Nöthen, Markus M., additional, O’Donovan, Michael C., additional, Oedegaard, Ketil J., additional, Olsson, Tomas, additional, Owen, Michael J., additional, Paciga, Sara A., additional, Pantelis, Chris, additional, Pato, Carlos, additional, Pato, Michele T., additional, Patrinos, George P., additional, Perlis, Roy H., additional, Posthuma, Danielle, additional, Ramos-Quiroga, Josep Antoni, additional, Reif, Andreas, additional, Reininghaus, Eva Z., additional, Ribasés, Marta, additional, Rietschel, Marcella, additional, Ripke, Stephan, additional, Rouleau, Guy A., additional, Saito, Takeo, additional, Schall, Ulrich, additional, Schalling, Martin, additional, Schofield, Peter R., additional, Schulze, Thomas G., additional, Scott, Laura J., additional, Scott, Rodney J., additional, Serretti, Alessandro, additional, Weickert, Cynthia Shannon, additional, Smoller, Jordan W., additional, Stefansson, Hreinn, additional, Stefansson, Kari, additional, Stordal, Eystein, additional, Streit, Fabian, additional, Sullivan, Patrick F., additional, Turecki, Gustavo, additional, Vaaler, Arne E., additional, Vieta, Eduard, additional, Vincent, John B., additional, Waldman, Irwin D., additional, Weickert, Thomas W., additional, Werge, Thomas, additional, Wray, Naomi R., additional, Zwart, John-Anker, additional, Biernacka, Joanna M., additional, Nurnberger, John I., additional, Cichon, Sven, additional, Edenberg, Howard J., additional, Stahl, Eli A., additional, McQuillin, Andrew, additional, Di Florio, Arianna, additional, Ophoff, Roel A., additional, and Andreassen, Ole A., additional

Published
2020
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30. Transcriptomic Changes Resulting From STK32B Overexpression Identify Pathways Potentially Relevant to Essential Tremor

Author

Liao, Calwing, primary, Sarayloo, Faezeh, additional, Vuokila, Veikko, additional, Rochefort, Daniel, additional, Akçimen, Fulya, additional, Diamond, Simone, additional, Houle, Gabrielle, additional, Laporte, Alexandre D., additional, Spiegelman, Dan, additional, He, Qin, additional, Catoire, Hélène, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2020
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31. Multiomics Analyses Identify Genes and Pathways Relevant to Essential Tremor

Author

Liao, Calwing, primary, Sarayloo, Faezeh, additional, Rochefort, Daniel, additional, Houle, Gabrielle, additional, Akçimen, Fulya, additional, He, Qin, additional, Laporte, Alexandre D., additional, Spiegelman, Dan, additional, Poewe, Werner, additional, Berg, Daniela, additional, Müller, Stefanie, additional, Hopfner, Franziska, additional, Deuschl, Günther, additional, Kuhlenbäeumer, Gregor, additional, Rajput, Alex, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2020
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32. Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Author

Akçimen, Fulya, primary, Martins, Sandra, additional, Liao, Calwing, additional, Bourassa, Cynthia V., additional, Catoire, Hélène, additional, Nicholson, Garth A., additional, Riess, Olaf, additional, Raposo, Mafalda, additional, França, Marcondes C., additional, Vasconcelos, João, additional, Lima, Manuela, additional, Lopes-Cendes, Iscia, additional, Saraiva-Pereira, Maria Luiza, additional, Jardim, Laura B., additional, Sequeiros, Jorge, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2020
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33. Investigation of the RFC1 Repeat Expansion in a Canadian and a Brazilian Ataxia Cohort: Identification of Novel Conformations

Author

Akçimen, Fulya, primary, Ross, Jay P., additional, Bourassa, Cynthia V., additional, Liao, Calwing, additional, Rochefort, Daniel, additional, Gama, Maria Thereza Drumond, additional, Dicaire, Marie-Josée, additional, Barsottini, Orlando G., additional, Brais, Bernard, additional, Pedroso, José Luiz, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2019
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34. Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

Author

Akçimen, Fulya, primary, Martins, Sandra, additional, Liao, Calwing, additional, Bourassa, Cynthia V., additional, Catoire, Hélène, additional, Nicholson, Garth A., additional, Riess, Olaf, additional, Raposo, Mafalda, additional, França, Marcondes C., additional, Vasconcelos, João, additional, Lima, Manuela, additional, Lopes-Cendes, Iscia, additional, Saraiva-Pereira, Maria Luiza, additional, Jardim, Laura B., additional, Sequeiros, Jorge, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2019
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38. Targeted sequencing reveals expanded genetic diversity of human transfer RNAs

Author

Berg, Matthew D., primary, Giguere, Daniel J., additional, Dron, Jacqueline S., additional, Lant, Jeremy T., additional, Genereaux, Julie, additional, Liao, Calwing, additional, Wang, Jian, additional, Robinson, John F., additional, Gloor, Gregory B., additional, Hegele, Robert A., additional, O’Donoghue, Patrick, additional, and Brandl, Christopher J., additional

Published
2019
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41. Investigation of the pathogenic RFC1 repeat expansion in a Canadian and a Brazilian ataxia cohort: identification of novel conformations

Author

Akçimen, Fulya, primary, Ross, Jay P., additional, Bourassa, Cynthia V., additional, Liao, Calwing, additional, Rochefort, Daniel, additional, Gama, Maria Thereza Drumond, additional, Dicarie, Marie-Josée, additional, Barsottini, Orlando G., additional, Brais, Bernard, additional, Pedroso, José Luiz, additional, Dion, Patrick A., additional, and Rouleau, Guy A., additional

Published
2019
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44. Expanded CAG Repeats in ATXN1, ATXN2, ATXN3, and HTT in the 1000 Genomes Project.

Author

Akçimen, Fulya, Ross, Jay P., Liao, Calwing, Spiegelman, Dan, Dion, Patrick A., and Rouleau, Guy A.

Abstract

Background: Spinocerebellar ataxia types 1, 2, 3 and Huntington disease are neurodegenerative disorders caused by expanded CAG repeats. Methods: We performed an in‐silico analysis of CAG repeats in ATXN1, ATXN2, ATXN3, and HTT using 30× whole‐=genome sequencing data of 2504 samples from the 1000 Genomes Project. Results: Seven HTT‐positive, 3 ATXN2‐positive, 1 ATXN3‐positive, and 6 possibly ATXN1‐positive samples were identified. No correlation was found between the repeat sizes of the different genes. The distribution of CAG alleles varied by ethnicity. Conclusion: Our results suggest that there may be asymptomatic small expanded repeats in almost 0.5% of these populations. © 2020 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Published
2021
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45. Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.

Author

Akçimen, Fulya, Chia, Ruth, Saez‐Atienzar, Sara, Ruffo, Paola, Rasheed, Memoona, Ross, Jay P., Liao, Calwing, Ray, Anindita, Dion, Patrick A., Scholz, Sonja W., Rouleau, Guy A., and Traynor, Bryan J.

Subjects
*RESTLESS legs syndrome, *GENOMICS, *WHOLE genome sequencing, *RISK assessment, *GENETIC correlations, *URINARY urge incontinence
Abstract

Objective Methods Results Interpretation Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility.We performed a whole‐genome sequencing and genome‐wide association meta‐analysis of RLS cases (n = 9,851) and controls (n = 38,957) in 3 population‐based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE).Genome‐wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (LMX1B, rs35196838, OR 1.14, 95% CI 1.09–1.19, p value = 2.2 × 10−9). Furthermore, a transcriptome‐wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p value = 5.4 × 10−7), depression (rg = 0.35, se = 0.06, p value = 2.17 × 10−8), and intelligence (rg = −0.20, se = 0.06, p value = 4.0 × 10−4).Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Published
2024
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47. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. 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M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. 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J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. 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Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022

49. The landscape of regional missense mutational intolerance quantified from 125,748 exomes.

Author

Chao KR, Wang L, Panchal R, Liao C, Abderrazzaq H, Ye R, Schultz P, Compitello J, Grant RH, Kosmicki JA, Weisburd B, Phu W, Wilson MW, Laricchia KM, Goodrich JK, Goldstein D, Goldstein JI, Vittal C, Poterba T, Baxter S, Watts NA, Solomonson M, Tiao G, Rehm HL, Neale BM, Talkowski ME, MacArthur DG, O'Donnell-Luria A, Karczewski KJ, Radivojac P, Daly MJ, and Samocha KE

Abstract

Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within genes that are specifically intolerant of missense variation 1-12 . Here, we leverage the patterns of rare missense variation in 125,748 individuals in the Genome Aggregation Database (gnomAD) 13 against a null mutational model to identify transcripts that display regional differences in missense constraint. Missense-depleted regions are enriched for ClinVar 14 pathogenic variants, de novo missense variants from individuals with neurodevelopmental disorders (NDDs) 15,16 , and complex trait heritability. Following ClinGen calibration recommendations for the ACMG/AMP guidelines, we establish that regions with less than 20% of their expected missense variation achieve moderate support for pathogenicity. We create a missense deleteriousness metric (MPC) that incorporates regional constraint and outperforms other deleteriousness scores at stratifying case and control de novo missense variation, with a strong enrichment in NDDs. These results provide additional tools to aid in missense variant interpretation.

Published
2024
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50. Genomic analysis identifies risk factors in restless legs syndrome.

Author

Akçimen F, Chia R, Saez-Atienzar S, Ruffo P, Rasheed M, Ross JP, Liao C, Ray A, Dion PA, Scholz SW, Rouleau GA, and Traynor BJ

Abstract

Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. Here, we present a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in three population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). Genome-wide association analysis identified nine independent risk loci, of which eight had been previously reported, and one was a novel risk locus ( LMX1B , rs35196838, OR = 1.14, 95% CI = 1.09-1.19, p -value = 2.2 × 10 -9 ). A genome-wide, gene-based common variant analysis identified GLO1 as an additional risk gene ( p -value = 8.45 × 10 -7 ). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1 . A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (r g = 0.40, se = 0.08, p -value = 5.4 × 10 -7 ), depression (r g = 0.35, se = 0.06, p -value = 2.17 × 10 -8 ), and intelligence (r g = -0.20, se = 0.06, p- value = 4.0 × 10 -4 ). Our study expands the understanding of the genetic architecture of RLS and highlights the contributions of common variants to this prevalent neurological disorder., Competing Interests: Conflict of interest: None.

Published
2023
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