55 results on '"Ripke, Stephan"'
Search Results
2. Increased risk of severe clinical course of COVID-19 in carriers of HLA-C*04:01
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Weiner 3rd, January, Suwalski, Phillip, Holtgrewe, Manuel, Rakitko, Alexander, Thibeault, Charlotte, Müller, Melina, Patriki, Dimitri, Quedenau, Claudia, Krüger, Ulrike, Ilinsky, Valery, Popov, Iaroslav, Balnis, Joseph, Jaitovich, Ariel, Helbig, Elisa T., Lippert, Lena J., Stubbemann, Paula, Real, Luis M., Macías, Juan, Pineda, Juan A., Fernandez-Fuertes, Marta, Wang, Xiaomin, Karadeniz, Zehra, Saccomanno, Jacopo, Doehn, Jan-Moritz, Hübner, Ralf-Harto, Hinzmann, Bernd, Salvo, Mauricio, Blueher, Anja, Siemann, Sandra, Jurisic, Stjepan, Beer, Juerg H., Rutishauser, Jonas, Wiggli, Benedikt, Schmid, Hansruedi, Danninger, Kathrin, Binder, Ronald, Corman, Victor M., Mühlemann, Barbara, Arjun Arkal, Rao, Fragiadakis, Gabriela K., Mick, Eran, Consortium COMET, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn M., Kangelaris, Kirsten N., Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Venkataramani, Urmila, García, Federico, Zyla, Joanna, Drosten, Christian, Alice, Braun, Jones, Terry C., Suttorp, Norbert, Witzenrath, Martin, Hippenstiel, Stefan, Zemojtel, Tomasz, Skurk, Carsten, Poller, Wolfgang, Borodina, Tatiana, Study Group Pa-COVID, Ripke, Stephan, Sander, Leif E., Beule, Dieter, Landmesser, Ulf, Guettouche, Toumy, Kurth, Florian, Heidecker, Bettina, [Weiner, January] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Beule, Dieter] Charite Univ Med Berlin, Core Unit Bioinformat Berlin, Berlin Inst Hlth, DE-10178 Berlin, Germany, [Suwalski, Phillip] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Mueller, Melina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Wang, Xiaomin] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Karadeniz, Zehra] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Skurk, Carsten] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Poller, Wolfgang] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Landmesser, Ulf] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Heidecker, Bettina] Charite Univ Med Berlin, Dept Cardiol, DE-12203 Berlin, Germany, [Suwalski, Phillip] Charite, Berliner Simulat & Trainingszentrum, DE-10117 Berlin, Germany, [Holtgrewe, Manuel] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Krueger, Ulrike] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Zemojtel, Tomasz] Charite Univ Med Berlin, Berlin Inst Hlth, Core Unit Genom Berlin, DE-10178 Berlin, Germany, [Rakitko, Alexander] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Ilinsky, Valery] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Popov, Iaroslav] Genotek Ltd, Nastavnicheskii Pereulok 17-1, R-105120 Moscow, Russia, [Thibeault, Charlotte] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Helbig, Elisa T.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Lippert, Lena J.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Stubbemann, Paula] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Saccomanno, Jacopo] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Doehn, Jan-Moritz] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Huebner, Ralf-Harto] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Suttorp, Norbert] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Witzenrath, Martin] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Hippenstiel, Stefan] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Sander, Leif E.] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Kurth, Florian] Charite Univ Med Berlin, Dept Infect Dis & Resp Med Berlin, DE-10117 Berlin, Germany, [Patriki, Dimitri] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Jurisic, Stjepan] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Beer, Juerg H.] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Rutishauser, Jonas] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Wiggli, Benedikt] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Schmid, Hansruedi] Kantonsspital Baden AG, Dept Med, CH-5404 Baden, Switzerland, [Quedenau, Claudia] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Borodina, Tatiana] Max Delbrueck Ctr Mol Med Berlin, DE-13125 Berlin, Germany, [Balnis, Joseph] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Jaitovich, Ariel] Albany Med Coll, Dept Mol & Cellular Physiol, Albany, NY 12208 USA, [Real, Luis M.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Macias, Juan] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Pineda, Juan A.] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Fernandez-Fuertes, Marta] Hosp Univ Valme, Unidad Clin Enfermedades Infecciosas & Microbiol, ES-41014 Seville, Spain, [Hinzmann, Bernd] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Salvo, Mauricio] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Blueher, Anja] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Siemann, Sandra] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Guettouche, Toumy] Roche Sequencing Solut, Pleasanton, CA 94588 USA, [Danninger, Kathrin] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Binder, Ronald] Klinikum Wels Grieskirchen, Dept Cardiol & Intens Care, Wels, Austria, [Corman, Victor M.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Muehlemann, Barbara] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Drosten, Christian] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] Charite Univ Med Berlin, Inst Virol, Charitepl 1, DE-10117 Berlin, Germany, [Arkal, Rao Arjun] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Krummel, Matthew F.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, ImmunoX Initiat, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Venkataramani, Urmila] Univ Calif San Francisco, CoLabs, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA, [Fragiadakis, Gabriela K.] Univ Calif San Francisco, Dept Med, Div Rheumatol, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Calfee, Carolyn S.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Hendrickson, Carolyn M.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Div Pulm Crit Care Allergy & Sleep Med, San Francisco, CA 94143 USA, [Mick, Eran] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Langelier, Charles R.] Univ Calif San Francisco, Div Infect Dis, San Francisco, CA 94143 USA, [Mick, Eran] Chan Zuckerberg Biohub, San Francisco, CA USA, [Langelier, Charles R.] Chan Zuckerberg Biohub, San Francisco, CA USA, [Erle, David J.] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Consortium COMET] COMET COVID 19 Multiphenotyping Effect Therapies, San Francisco, CA USA, [Erle, David J.] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA, [Erle, David J.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Kangelaris, Kirsten N.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA, [Arkal, Rao Arjun] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Krummel, Matthew F.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA, [Woodruff, Prescott G.] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA, [Garcia, Federico] Hosp Univ Clin San Cecilio, Inst Invest Ibs Granada, Granada, Spain, [Zyla, Joanna] Silesian Tech Univ, Dept Data Sci & Engn, Gliwice, Poland, [Alice, Braun] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Ripke, Stephan] Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Charitepl 1, DE-10117 Berlin, Germany, [Jones, Terry C.] German Ctr Infect Res DZIF, Associated Partner Site, D-10117 Berlin, Germany, [Jones, Terry C.] Univ Cambridge, Ctr Pathogen Evolut, Dept Zool, Downing St, Cambridge CB2 3EJ, England, [Study Grp Pa-COVID] Pa COVID Study Grp, San Francisco, CA USA, [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet, Boston, MA 02114 USA, [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA, [Landmesser, Ulf] Charite, Berlin Inst Hlth, Berlin, Germany, Roche Sequencing Solutions, Inc., Swiss National Science Foundation, Berlin Institutes of Health (B.I.H.), National Institutes of Health: NIH, Silesian University of Technology grant for Support and Development of Research Potential, NIAID-NIH CEIRS contract, NIH, German Research Foundation, German Ministry of Education and Research (BMBF), Berlin Institute of Health (CM-COVID), German Research Foundation (DFG), and Open Access Publication Fund of Charite - Universitatsmedizin Berlin
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SARS-CoV-2 ,Prevention ,Major histocompatibility complex ,Human Genome ,COVID-19 ,Pneumonia ,intubation ,Human Leukocyte Antigen ,Coronavirus ,Vaccine Related ,Emerging Infectious Diseases ,Infectious Diseases ,Good Health and Well Being ,Clinical Research ,FOS: Biological sciences ,Human Leukocyte Antigen  ,Genetics ,Pneumonia & Influenza ,2.1 Biological and endogenous factors ,Viral load ,Aetiology ,Lung ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,Research Paper - Abstract
Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing urgency to identify pathophysiological characteristics leading to severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors that affect individual immune response to SARS-CoV-2. We sought to evaluate this hypothesis by conducting a multicenter study using HLA sequencing. Methods: We analyzed the association between COVID-19 severity and HLAs in 435 individuals from Germany (n = 135), Spain (n = 133), Switzerland (n = 20) and the United States (n = 147), who had been enrolled from March 2020 to August 2020. This study included patients older than 18 years, diagnosed with COVID19 and representing the full spectrum of the disease. Finally, we tested our results by meta-analysing data from prior genome-wide association studies (GWAS). Findings: We describe a potential association of HLA-C*04:01 with severe clinical course of COVID-19. Carriers of HLA-C*04:01 had twice the risk of intubation when infected with SARS-CoV-2 (risk ratio 1.5 [95% CI 1.1-2.1], odds ratio 3.5 [95% CI 1.9-6.6], adjusted p-value = 0.0074). These findings are based on data from four countries and corroborated by independent results from GWAS. Our findings are biologically plausible, as HLA-C*04:01 has fewer predicted bindings sites for relevant SARS-CoV-2 peptides compared to other HLA alleles. Interpretation: HLA-C*04:01 carrier state is associated with severe clinical course in SARS-CoV-2. Our findings suggest that HLA class I alleles have a relevant role in immune defense against SARS-CoV-2. Funding: Funded by Roche Sequencing Solutions, Inc. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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- 2021
3. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
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Mullins, Niamh, Kang, JooEun, Campos, Adrian I, Coleman, Jonathan RI, Edwards, Alexis C, Galfalvy, Hanga, Levey, Daniel F, Lori, Adriana, Shabalin, Andrey, Starnawska, Anna, Su, Mei-Hsin, Watson, Hunna J, Adams, Mark, Awasthi, Swapnil, Gandal, Michael, Hafferty, Jonathan D, Hishimoto, Akitoyo, Kim, Minsoo, Okazaki, Satoshi, Otsuka, Ikuo, Ripke, Stephan, Ware, Erin B, Bergen, Andrew W, Berrettini, Wade H, Bohus, Martin, Brandt, Harry, Chang, Xiao, Chen, Wei J, Chen, Hsi-Chung, Crawford, Steven, Crow, Scott, DiBlasi, Emily, Duriez, Philibert, Fernández-Aranda, Fernando, Fichter, Manfred M, Gallinger, Steven, Glatt, Stephen J, Gorwood, Philip, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A, Hwu, Hai-Gwo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Keel, Pamela K, Kennedy, James L, Klump, Kelly L, Li, Dong, Liao, Shih-Cheng, Lieb, Klaus, Lilenfeld, Lisa, Liu, Chih-Min, Magistretti, Pierre J, Marshall, Christian R, Mitchell, James E, Monson, Eric T, Myers, Richard M, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W, Schmahl, Christian, Sokolowski, Marcus, Strober, Michael, Thornton, Laura M, Treasure, Janet, Tsuang, Ming T, Witt, Stephanie H, Woodside, D Blake, Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Air, Tracy M, Alda, Martin, Alfredsson, Lars, Andreassen, Ole A, Anjorin, Adebayo, Appadurai, Vivek, Soler Artigas, María, Van der Auwera, Sandra, Azevedo, M Helena, Bass, Nicholas, Bau, Claiton HD, Baune, Bernhard T, Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M, Bigdeli, Tim B, Binder, Elisabeth B, Boehnke, Michael, Boks, Marco P, Bosch, Rosa, and Braff, David L
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Genetic correlation ,Genome-wide association study ,Medical and Health Sciences ,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ,Risk Factors ,Polygenicity ,Behavioral and Social Science ,Eating Disorders Working Group of the Psychiatric Genomics Consortium ,Suicide attempt ,Genetics ,German Borderline Genomics Consortium ,Humans ,2.1 Biological and endogenous factors ,Polymorphism ,Aetiology ,Attempted ,Pleiotropy ,Psychiatry ,Depressive Disorder ,MVP Suicide Exemplar Workgroup ,Mental Disorders ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Major ,Single Nucleotide ,Biological Sciences ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Brain Disorders ,Suicide ,Mental Health ,Good Health and Well Being ,VA Million Veteran Program - Abstract
BackgroundSuicide 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.MethodsWe 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.ResultsTwo 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.ConclusionsOur 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.
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- 2022
4. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
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van Rheenen, Wouter, van der Spek, Rick AA, Bakker, Mark K, van Vugt, Joke JFA, Hop, Paul J, Zwamborn, Ramona AJ, de Klein, Niek, Westra, Harm-Jan, Bakker, Olivier B, Deelen, Patrick, Shireby, Gemma, Hannon, Eilis, Moisse, Matthieu, Baird, Denis, Restuadi, Restuadi, Dolzhenko, Egor, Dekker, Annelot M, Gawor, Klara, Westeneng, Henk-Jan, Tazelaar, Gijs HP, van Eijk, Kristel R, Kooyman, Maarten, Byrne, Ross P, Doherty, Mark, Heverin, Mark, Al Khleifat, Ahmad, Iacoangeli, Alfredo, Shatunov, Aleksey, Ticozzi, Nicola, Cooper-Knock, Johnathan, Smith, Bradley N, Gromicho, Marta, Chandran, Siddharthan, Pal, Suvankar, Morrison, Karen E, Shaw, Pamela J, Hardy, John, Orrell, Richard W, Sendtner, Michael, Meyer, Thomas, Başak, Nazli, van der Kooi, Anneke J, Ratti, Antonia, Fogh, Isabella, Gellera, Cinzia, Lauria, Giuseppe, Corti, Stefania, Cereda, Cristina, Sproviero, Daisy, D'Alfonso, Sandra, Sorarù, Gianni, Siciliano, Gabriele, Filosto, Massimiliano, Padovani, Alessandro, Chiò, Adriano, Calvo, Andrea, Moglia, Cristina, Brunetti, Maura, Canosa, Antonio, Grassano, Maurizio, Beghi, Ettore, Pupillo, Elisabetta, Logroscino, Giancarlo, Nefussy, Beatrice, Osmanovic, Alma, Nordin, Angelica, Lerner, Yossef, Zabari, Michal, Gotkine, Marc, Baloh, Robert H, Bell, Shaughn, Vourc'h, Patrick, Corcia, Philippe, Couratier, Philippe, Millecamps, Stéphanie, Meininger, Vincent, Salachas, François, Mora Pardina, Jesus S, Assialioui, Abdelilah, Rojas-García, Ricardo, Dion, Patrick A, Ross, Jay P, Ludolph, Albert C, Weishaupt, Jochen H, Brenner, David, Freischmidt, Axel, Bensimon, Gilbert, Brice, Alexis, Durr, Alexandra, Payan, Christine AM, Saker-Delye, Safa, Wood, Nicholas W, Topp, Simon, Rademakers, Rosa, Tittmann, Lukas, Lieb, Wolfgang, Franke, Andre, Ripke, Stephan, Braun, Alice, and Kraft, Julia
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Male ,PARALS Consortium ,Glutamine ,Quantitative Trait Loci ,Neurodegenerative ,Medical and Health Sciences ,Rare Diseases ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,SLAGEN Consortium ,RNA-Seq ,Aetiology ,SLALOM Consortium ,Neurons ,Prevention ,Amyotrophic Lateral Sclerosis ,Human Genome ,Neurosciences ,Brain ,Neurodegenerative Diseases ,Mendelian Randomization Analysis ,Biological Sciences ,Brain Disorders ,Cholesterol ,SLAP Consortium ,Mutation ,Neurological ,Disease Progression ,Female ,ALS ,Microsatellite Repeats ,Genome-Wide Association Study ,Developmental Biology - Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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- 2021
5. Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium
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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, Schizophrenia Working Group of the Psychiatric Genomics Consortium, and Fanous, Ayman H
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Adult ,Cigarettes per day ,Nerve Tissue Proteins ,Smoking initiation ,Medical and Health Sciences ,Substance Misuse ,Tobacco ,Behavioral and Social Science ,Genetics ,Humans ,GWAS ,Genetic Predisposition to Disease ,Polymorphism ,Pleiotropy ,Psychiatry ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Tobacco Smoke and Health ,Prevention ,Smoking ,Human Genome ,Psychology and Cognitive Sciences ,Membrane Proteins ,Genomics ,Single Nucleotide ,Serious Mental Illness ,Brain Disorders ,Phenotype ,Mental Health ,Good Health and Well Being ,Schizophrenia ,Genome-Wide Association Study ,Biotechnology - 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.
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- 2021
6. Differential predictors for alcohol use in adolescents as a function of familial risk
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Tschorn, Mira, Lorenz, Robert C., O’Reilly, Paul F., Reichenberg, Abraham, Quinlan, Erin B., Flor, Herta, Grigis, Antoine, Garavan, Hugh, Ittermann, Bernd, Papadopoulos Orfanos, Dimitri, Poustka, Luise, Millenet, Sabina, Smolka, Michael N., Whelan, Robert, Schumann, Gunter, Rapp, Michael A., Robbins, Trevor, Dalley, Jeffrey, Subramaniam, Naresh, Theobald, David, Mann, Karl, Bach, Christiane, Struve, Maren, Banaschewski, Tobias, Rietschel, Marcella, Spanagel, Rainer, Nees, Frauke, Fauth-Bühler, Mira, Grimmer, Yvonne, Lathrop, Mark, Heinz, Andreas, Albrecht, Lisa, Ivanov, Nikolay, Strache, Nicole, Rapp, Michael, Ströhle, Andreas, Reuter, Jan, Gallinat, Jürgen, Walter, Henrik, Gemmeke, Isabel, Genauck, Alexander, Parchetka, Caroline, Weiß, Katharina, Kruschwitz, Johann, Raffaelli, Bianca, Isci, Alev, Daedelow, Laura, Barbot, Alexis, Thyreau, Benjamin, Schwartz, Yannick, Lalanne, Christophe, Frouin, Vincent, Orfanos, Dimitri Papadopoulos, Rogers, John, Ireland, James, Lanzerath, Dirk, Feng, Jianfeng, Martinot, Jean-Luc, Bricaud, Zuleima, Briand, Fanny Gollier, LemaÎtre, Hervé, Miranda, Ruben, Artiges, Eric, Massicotte, Jessica, Martinot, Marie-Laure Paillère, Vulser, Helene, Pentillä, Jani, Filippi, Irina, Galinowski, André, Bezivin, Pauline, Cattrell, Anna, Jia, Tianye, Desrivières, Sylvane, Werts, Helen, Topper, Lauren, Reed, Laurence, Andrew, Chris, Mallik, Catherine, Ruggeri, Barbara, Nymberg, Charlotte, Barker, Gareth, Conrod, Patricia J., Smith, Lindsay, Loth, Eva, Havatzias, Stephanie, Shekarrizi, Sheyda, Kitson, Emily, Robinson, Alice, Hall, Deborah, Rubino, Chiara, Wright, Hannah, Stueber, Kerstin, Hanratty, Eanna, Kennedy, Eleanor, De Carvahlo, Fabiana Mesquita, Stringaris, Argyris, Robert, Gabriel, Ing, Alex, Macare, Christine, Xu, Bing, Yu, Tao, Quinlan, Erin Burke, Constant, Patrick, Aydin, Semiha, Brühl, Ruediger, Ihlenfeld, Albrecht, Walaszek, Bernadeta, Smolka, Michael, Hübner, Thomas, Müller, Kathrin, Ripke, Stephan, Jurk, Sarah, Mennigen, Eva, Schmidt, Dirk, Vetter, Nora, Ziesch, Veronika, Fröhner, Juliane H., Bokde, Arun L. W., Carter, Daniel, Walsh, Emily, O’Driscoll, Susanne, Agan, Maria Leonora Fatimah, McMorrow, Mairead, Nugent, Sinead, Connolly, Colm, Dooley, Eoin, Cremen, Clodagh, Jones, Jennifer, O’Keefe, John, O’Connor, Martin, Poline, Jean-Baptiste, Büchel, Christian, Bromberg, Uli, Fadai, Tahmine, Yacubian, Juliana, Schneider, Sophia, Lobatchewa, Maria, Lawrence, Claire, Newman, Craig, Head, Kay, Heym, Nadja, Gowland, Penny, Stedman, Alicia, Kaviani, Mehri, Taplin, Susannah, Stephens, Dai, Paus, Tomáš, Pausova, Zdenka, Tahmasebi, Amir, Banaschewski, Tobias [0000-0003-4595-1144], Bokde, Arun L. W. [0000-0003-0114-4914], Quinlan, Erin B. [0000-0003-2927-1632], Desrivières, Sylvane [0000-0002-9120-7060], Gowland, Penny [0000-0002-4900-4817], Martinot, Jean-Luc [0000-0002-0136-0388], Artiges, Eric [0000-0003-4461-7646], Nees, Frauke [0000-0002-7796-8234], Papadopoulos Orfanos, Dimitri [0000-0002-1242-8990], Fröhner, Juliane H. [0000-0002-8493-6396], Smolka, Michael N. [0000-0001-5398-5569], Walter, Henrik [0000-0002-9403-6121], Heinz, Andreas [0000-0001-5405-9065], Rapp, Michael A. [0000-0003-0106-966X], and Apollo - University of Cambridge Repository
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631/208 ,article ,59/36 ,45/23 ,631/378 ,631/477 ,692/699/476/5 - Abstract
Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.
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- 2021
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- View/download PDF
7. Differential predictors for alcohol use in adolescents as a function of familial risk
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Tschorn, Mira, Lorenz, Robert C., O’Reilly, Paul F., Reichenberg, Abraham, Banaschewski, Tobias, Bokde, Arun L. W., Quinlan, Erin B., Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Ittermann, Bernd, Martinot, Jean-Luc, Artiges, Eric, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Poustka, Luise, Millenet, Sabina, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Heinz, Andreas, Rapp, Michael A., Robbins, Trevor, Dalley, Jeffrey, Subramaniam, Naresh, Theobald, David, Mann, Karl, Bach, Christiane, Struve, Maren, Rietschel, Marcella, Spanagel, Rainer, Fauth-Bühler, Mira, Grimmer, Yvonne, Lathrop, Mark, Albrecht, Lisa, Ivanov, Nikolay, Strache, Nicole, Rapp, Michael, Ströhle, Andreas, Reuter, Jan, Gallinat, Jürgen, Gemmeke, Isabel, Genauck, Alexander, Parchetka, Caroline, Weiß, Katharina, Kruschwitz, Johann, Raffaelli, Bianca, Isci, Alev, Daedelow, Laura, Barbot, Alexis, Thyreau, Benjamin, Schwartz, Yannick, Lalanne, Christophe, Frouin, Vincent, Orfanos, Dimitri Papadopoulos, Rogers, John, Ireland, James, Lanzerath, Dirk, Feng, Jianfeng, Bricaud, Zuleima, Briand, Fanny Gollier, LemaÎtre, Hervé, Miranda, Ruben, Massicotte, Jessica, Martinot, Marie-Laure Paillère, Vulser, Helene, Pentillä, Jani, Filippi, Irina, Galinowski, André, Bezivin, Pauline, Cattrell, Anna, Jia, Tianye, Werts, Helen, Topper, Lauren, Reed, Laurence, Andrew, Chris, Mallik, Catherine, Ruggeri, Barbara, Nymberg, Charlotte, Barker, Gareth, Conrod, Patricia J., Smith, Lindsay, Loth, Eva, Havatzias, Stephanie, Shekarrizi, Sheyda, Kitson, Emily, Robinson, Alice, Hall, Deborah, Rubino, Chiara, Wright, Hannah, Stueber, Kerstin, Hanratty, Eanna, Kennedy, Eleanor, de Carvahlo, Fabiana Mesquita, Stringaris, Argyris, Robert, Gabriel, Ing, Alex, Macare, Christine, Xu, Bing, Yu, Tao, Quinlan, Erin Burke, Constant, Patrick, Aydin, Semiha, Brühl, Ruediger, Ihlenfeld, Albrecht, Walaszek, Bernadeta, Smolka, Michael, Hübner, Thomas, Müller, Kathrin, Ripke, Stephan, Jurk, Sarah, Mennigen, Eva, Schmidt, Dirk, Vetter, Nora, Ziesch, Veronika, Carter, Daniel, Walsh, Emily, O’Driscoll, Susanne, Agan, Maria Leonora Fatimah, McMorrow, Mairead, Nugent, Sinead, Connolly, Colm, Dooley, Eoin, Cremen, Clodagh, Jones, Jennifer, O’Keefe, John, O’Connor, Martin, Poline, Jean-Baptiste, Büchel, Christian, Bromberg, Uli, Fadai, Tahmine, Yacubian, Juliana, Schneider, Sophia, Lobatchewa, Maria, Lawrence, Claire, Newman, Craig, Head, Kay, Heym, Nadja, Stedman, Alicia, Kaviani, Mehri, Taplin, Susannah, Stephens, Dai, Paus, Tomáš, Pausova, Zdenka, Tahmasebi, Amir, Banaschewski, Tobias [0000-0003-4595-1144], Bokde, Arun LW [0000-0003-0114-4914], Quinlan, Erin B [0000-0003-2927-1632], Desrivières, Sylvane [0000-0002-9120-7060], Gowland, Penny [0000-0002-4900-4817], Martinot, Jean-Luc [0000-0002-0136-0388], Artiges, Eric [0000-0003-4461-7646], Nees, Frauke [0000-0002-7796-8234], Papadopoulos Orfanos, Dimitri [0000-0002-1242-8990], Fröhner, Juliane H [0000-0002-8493-6396], Smolka, Michael N [0000-0001-5398-5569], Walter, Henrik [0000-0002-9403-6121], Heinz, Andreas [0000-0001-5405-9065], Rapp, Michael A [0000-0003-0106-966X], and Apollo - University of Cambridge Repository
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Adolescent ,Alcohol Drinking ,RJ ,media_common.quotation_subject ,Addiction ,Impulsivity ,Article ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,HV ,Reward ,Risk Factors ,medicine ,Genetics ,Personality ,Psychology ,Humans ,Genetic Predisposition to Disease ,Family history ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,media_common ,Extraversion and introversion ,Alcohol Use Disorders Identification Test ,Cognition ,medicine.disease ,030227 psychiatry ,Substance abuse ,Psychiatry and Mental health ,Alcoholism ,Cohort ,Impulsive Behavior ,medicine.symptom ,030217 neurology & neurosurgery ,Clinical psychology ,Neuroscience - Abstract
Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.
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- 2021
8. Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients
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Aschenbrenner, Anna C, Mouktaroudi, Maria, Saridaki, Maria, McHardy, Alice, Mertes, Christian, Nöthen, Markus, Nürnberg, Peter, Ohler, Uwe, Ossowski, Stephan, Overmann, Jörg, Pfeffer, Klaus, Poetsch, Anna R, Pühler, Alfred, Knoll, Rainer, Rajewsky, Nikolaus, Ralser, Markus, Rieß, Olaf, Ripke, Stephan, Nunes da Rocha, Ulisses, Rosenstiel, Philip, Saliba, Antoine-Emmanuel, Sander, Leif Erik, Sawitzki, Birgit, Schiffer, Philipp, Pecht, Tal, Schneider, Wulf, Schulte, Eva-Christina, Schultze, Joachim L, Sczyrba, Alexander, Singh, Yogesh, Sonnabend, Michael, Stegle, Oliver, Stoye, Jens, Theis, Fabian, Vehreschild, Janne, Kapellos, Theodore S, Vogel, Jörg, von Kleist, Max, Walker, Andreas, Walter, Jörn, Wieczorek, Dagmar, Winkler, Sylke, Ziebuhr, John, Doulou, Sarandia, Kröger, Charlotte, Herbert, Miriam, Holsten, Lisa, Horne, Arik, Gemünd, Ioanna D, Krämer, Benjamin, Rovina, Nikoletta, Agrawal, Shobhit, Dahm, Kilian, van Uelft, Martina, Drews, Anna, Lenkeit, Lena, Bruse, Niklas, Gerretsen, Jelle, Gierlich, Jannik, Becker, Matthias, Oestreich, Marie, Händler, Kristian, Kraut, Michael, Theis, Heidi, Mengiste, Simachew, De Domenico, Elena, Schulte-Schrepping, Jonas, Seep, Lea, Raabe, Jan, Hoffmeister, Christoph, ToVinh, Michael, Antonakos, Nikolaos, Keitel, Verena, Rieke, Gereon, Talevi, Valentina, Skowasch, Dirk, Aziz, N. Ahmad, Pickkers, Peter, van de Veerdonk, Frank L, Netea, Mihai G, Kox, Matthijs, Nuesch-Germano, Melanie, Breteler, Monique M B, Nattermann, Jacob, Koutsoukou, Antonia, Giamarellos-Bourboulis, Evangelos J, Ulas, Thomas, Initiative, German COVID-19 Omics, Altmüller, Janine, Angelov, Angel, Bals, Robert, Bartholomäus, Alexander, Gkizeli, Konstantina, Becker, Anke, Bitzer, Michael, Bonifacio, Ezio, Bork, Peer, Casadei, Nicolas, Clavel, Thomas, Colome-Tatche, Maria, Diefenbach, Andreas, Dilthey, Alexander, Fischer, Nicole, Bonaguro, Lorenzo, Förstner, Konrad, Franzenburg, Sören, Frick, Julia-Stefanie, Gabernet, Gisela, Gagneur, Julien, Ganzenmüller, Tina, Göpel, Siri, Goesmann, Alexander, Hain, Torsten, Heimbach, André, Reusch, Nico, Hummel, Michael, Iftner, Angelika, Iftner, Thomas, Janssen, Stefan, Kalinowski, Jörn, Kallies, René, Kehr, Birte, Keller, Andreas, Kim-Hellmuth, Sarah, Klein, Christoph, Baßler, Kevin, Kohlbacher, Oliver, Köhrer, Karl, Korbel, Jan, Kühnert, Denise, Kurth, Ingo, Landthaler, Markus, Li, Yang, Ludwig, Kerstin, Makarewicz, Oliwia, and Marz, Manja
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Cancer Research ,Neutrophils ,virology [COVID-19] ,cytology [Neutrophils] ,Drug repurposing ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,lcsh:Medicine ,chemistry [RNA] ,Severity of Illness Index ,pathology [COVID-19] ,Transcriptome ,0302 clinical medicine ,Genetics (clinical) ,Whole blood ,immunology [Neutrophils] ,Principal Component Analysis ,0303 health sciences ,metabolism [Neutrophils] ,Up-Regulation ,3. Good health ,Co-expression analysis ,Phenotype ,medicine.anatomical_structure ,metabolism [RNA] ,030220 oncology & carcinogenesis ,Molecular disease phenotypes ,Molecular Medicine ,Technology Platforms ,lcsh:QH426-470 ,blood [RNA] ,Down-Regulation ,drug therapy [COVID-19] ,Granulocyte ,Antiviral Agents ,03 medical and health sciences ,Immune system ,All institutes and research themes of the Radboud University Medical Center ,Severity of illness ,Genetics ,medicine ,Humans ,ddc:610 ,Molecular Biology ,030304 developmental biology ,Sequence Analysis, RNA ,business.industry ,Research ,lcsh:R ,Drug Repositioning ,Case-control study ,Blood transcriptomics ,COVID-19 ,Human genetics ,COVID-19 Drug Treatment ,therapeutic use [Antiviral Agents] ,lcsh:Genetics ,Respiratory failure ,Cardiovascular and Metabolic Diseases ,Case-Control Studies ,Immunology ,RNA ,Stratification ,business ,Granulocytes - Abstract
Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.
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- 2021
9. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
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Munn-Chernoff, Melissa A, Johnson, Emma C, Chou, Yi-Ling, Coleman, Jonathan RI, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C
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Drug Abuse (NIDA Only) ,Substance-Related Disorders ,Eating Disorders ,substance use ,Medical and Health Sciences ,Linkage Disequilibrium ,Feeding and Eating Disorders ,Substance Misuse ,Alcohol Use and Health ,Risk Factors ,Clinical Research ,2.3 Psychological ,mental disorders ,Tobacco ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Polymorphism ,Nutrition ,Depressive Disorder ,Tobacco Smoke and Health ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Substance Abuse ,Major ,Tobacco Use Disorder ,Single Nucleotide ,genetic correlation ,Brain Disorders ,Alcoholism ,Good Health and Well Being ,Phenotype ,Mental Health ,Schizophrenia ,social and economic factors ,Genome-Wide Association Study - Abstract
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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- 2021
10. The IMAGEN study: a decade of imaging genetics in adolescents
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Mascarell Maričić, Lea, Walter, Henrik, Rosenthal, Annika, Ripke, Stephan, Quinlan, Erin Burke, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Bromberg, Uli, Büchel, Christian, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Itterman, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Smolka, Michael N., Fröhner, Juliane H., Whelan, Robert, Kaminski, Jakob, Schumann, Gunter, Heinz, Andreas, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bruehl, Ruediger, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Fadai, Tahmine, Gallinat, Jürgen, Briand, Fanny Gollier, Gowland, Penny, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ireland, James, Ittermann, Bernd, Jia, Tianye, Lathrop, Mark, Lanzerath, Dirk, Lawrence, Claire, Lemaitre, Hervé, Lüdemann, Katharina, Macare, Christine, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mennigen, Eva, de Carvahlo, Fabiana Mesquita, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Paillere, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Poline, Jean-Baptiste, Rapp, Michael, Robert, Gabriel, Reuter, Jan, Rietschel, Marcella, Robbins, Trevor, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schumann, MarkGunter, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Topper, Lauren, Williams, Steve, Yacubian, Juliana, Zilbovicius, Monica, Wong, C. Peng, Lubbe, Steven, Martinez-Medina, Lourdes, Fernandes, Alinda, and Tahmasebi, Amir
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Time Factors ,Adolescent ,Imaging genetics ,Brain Structure and Function ,Neuroimaging ,Cohort Studies ,Cellular and Molecular Neuroscience ,Reward ,Genetics ,Humans ,Psychology ,Multicenter Studies as Topic ,Generalizability theory ,Molecular Biology ,Reproducibility of Results ,Small sample ,Anticipation ,Psychiatry and Mental health ,Sample size determination ,Adolescent Behavior ,Cohort ,Brain size ,Perspective ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,Clinical psychology ,Neuroscience - Abstract
Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.
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- 2020
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11. Classical Human Leukocyte Antigen Alleles And C4 Haplotypes Are Not Significantly Associated With Depression
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Glanville, Kylie P., Coleman, Jonathan R.I., Hanscombe, Ken B., Euesden, Jack, Choi, Shing Wan, Purves, Kirstin L., Breen, Gerome, Air, Tracy M., Andlauer, Till F.M., Baune, Bernhard T., Binder, Elisabeth B., Blackwood, Douglas H.R., Boomsma, Dorret I., Buttenschøn, Henriette N., Colodro-Conde, Lucía, Dannlowski, Udo, Direk, Nese, Dunn, Erin C., Forstner, Andreas J., de Geus, Eco J.C., Grabe, Hans J., Hamilton, Steven P., Jones, Ian, Jones, Lisa A., Knowles, James A., Kutalik, Zoltán, Levinson, Douglas F., Lewis, Glyn, Lind, Penelope A., Lucae, Susanne, Magnusson, Patrik K., McGuffin, Peter, McIntosh, Andrew M., Milaneschi, Yuri, Mors, Ole, Mostafavi, Sara, Müller-Myhsok, Bertram, Pedersen, Nancy L., Penninx, Brenda W.J.H., Potash, James B., Preisig, Martin, Ripke, Stephan, Shi, Jianxin, Shyn, Stanley I., Smoller, Jordan W., Streit, Fabian, Sullivan, Patrick F., Tiemeier, Henning, Uher, Rudolf, Van der Auwera, Sandra, Weissman, Myrna M., O'Reilly, Paul F., Lewis, Cathryn M., Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T.F., Bigdeli, Tim B., Bryois, Julien, Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Dolan, Conor V., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., and Foo, Jerome C.
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- 2020
- Full Text
- View/download PDF
12. Author Correction: A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
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Wightman, Douglas P., Jansen, Iris E., Savage, Jeanne E., Shadrin, Alexey A., Bahrami, Shahram, Holland, Dominic, Rongve, Arvid, Børte, Sigrid, Winsvold, Bendik S., Drange, Ole Kristian, Martinsen, Amy E., Skogholt, Anne Heidi, Willer, Cristen, Bråthen, Geir, Bosnes, Ingunn, Nielsen, Jonas Bille, Fritsche, Lars G., Thomas, Laurent F., Pedersen, Linda M., Gabrielsen, Maiken E., Johnsen, Marianne Bakke, Meisingset, Tore Wergeland, Zhou, Wei, Proitsi, Petroula, Hodges, Angela, Dobson, Richard, Velayudhan, Latha, Heilbron, Karl, Auton, Adam, Agee, Michelle, Aslibekyan, Stella, Babalola, Elizabeth, Bell, Robert K., Bielenberg, Jessica, Bryc, Katarzyna, Bullis, Emily, Cameron, Briana, Coker, Daniella, Partida, Gabriel Cuellar, Dhamija, Devika, Das, Sayantan, Elson, Sarah L., Filshtein, Teresa, Fletez-Brant, Kipper, Fontanillas, Pierre, Freyman, Will, Gandhi, Pooja M., Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Kukar, Katelyn, Lane, Vanessa, Lin, Keng-Han, Lowe, Maya, Luff, Marie K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Micheletti, Steven J., Moreno, Meghan E., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., O’Connell, Jared, Petrakovitz, Aaron A., Poznik, G. David, Schumacher, Morgan, Shastri, Anjali J., Shelton, Janie F., Shi, Jingchunzi, Shringarpure, Suyash, Tian, Chao, Tran, Vinh, Tung, Joyce Y., Wang, Xin, Wang, Wei, Weldon, Catherine H., Wilton, Peter, Sealock, Julia M., Davis, Lea K., Pedersen, Nancy L., Reynolds, Chandra A., Karlsson, Ida K., Magnusson, Sigurdur, Stefansson, Hreinn, Thordardottir, Steinunn, Jonsson, Palmi V., Snaedal, Jon, Zettergren, Anna, Skoog, Ingmar, Kern, Silke, Waern, Margda, Zetterberg, Henrik, Blennow, Kaj, Stordal, Eystein, Hveem, Kristian, Zwart, John-Anker, Athanasiu, Lavinia, Selnes, Per, Saltvedt, Ingvild, Sando, Sigrid B., Ulstein, Ingun, Djurovic, Srdjan, Fladby, Tormod, Aarsland, Dag, Selbæk, Geir, Ripke, Stephan, Stefansson, Kari, Andreassen, Ole A., and Posthuma, Danielle
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Genetics ,Published Erratum ,MEDLINE ,Genome-wide association study ,Disease ,Biology - Abstract
In the version of this Article initially published, the author list and affiliations were incomplete. Karl Heilbron and Adam Auton, both with 23andMe, Inc., have been added to the author list. Further, the location for the 23andMe Research Team, now reading “Sunnyvale, CA” initially appeared as Mountain View, CA. The changes have been made to the online version of the paper. *A list of authors and their affiliations appears online.
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- 2021
13. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
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Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan RI, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Anorexia Nervosa Genetics Initiative, Hanscombe, Ken B, Purves, Kirstin L, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Adan, Roger AH, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver SP, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien JH, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klareskog, Lars, Klump, Kelly L, Knudsen, Gun Peggy S, and La Via, Maria C
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Adult ,Male ,Anorexia Nervosa ,Eating Disorders ,Quantitative Trait Loci ,Medical and Health Sciences ,Body Mass Index ,Metabolic Diseases ,Clinical Research ,Anorexia Nervosa Genetics Initiative ,Eating Disorders Working Group of the Psychiatric Genomics Consortium ,Genetics ,Humans ,Genetic Predisposition to Disease ,Nutrition ,Pediatric ,Mental Disorders ,Prevention ,Human Genome ,Genomics ,Biological Sciences ,Prognosis ,Serious Mental Illness ,Brain Disorders ,Anorexia ,Phenotype ,Mental Health ,Case-Control Studies ,Female ,Genome-Wide Association Study ,Developmental Biology - Abstract
Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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- 2019
14. GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
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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, M.R.C.Psych, 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, Dr.Med.Sc, 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, Dipl.-Psych, 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, and Kahn, René S
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Male ,Multifactorial Inheritance ,Bipolar Disorder ,Polygenic Risk Scoring ,Medical and Health Sciences ,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ,Psychiatric Genomics Consortium ,Risk Factors ,2.3 Psychological ,Genetics ,Dipl.-Psych ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Attempted ,Psychiatry ,Dr.Med.Sc ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Depressive Disorder ,Mood Disorders ,Depression ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Major ,Serious Mental Illness ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Brain Disorders ,Suicide ,Mental Health ,Good Health and Well Being ,Case-Control Studies ,Schizophrenia ,Female ,M.R.C.Psych ,social and economic factors ,Genome-Wide Association Study - 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.
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- 2019
15. Publisher Correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
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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, GERAD1 Consortium, CRESTAR Consortium, Collier, David A, Rujescu, Dan, Kirov, George, Owen, Michael J, O'Donovan, Michael C, and Walters, James TR
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CRESTAR Consortium ,Biological Sciences ,GERAD1 Consortium ,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.
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- 2019
16. Genome-wide association study identifies 30 loci associated with bipolar disorder
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Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders
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Male ,Bipolar Disorder ,Medical and Health Sciences ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,eQTLGen Consortium ,Depressive Disorder ,Systems Biology ,Human Genome ,Major ,Single Nucleotide ,Biological Sciences ,Serious Mental Illness ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Brain Disorders ,Mental Health ,Psychotic Disorders ,Genetic Loci ,Case-Control Studies ,Schizophrenia ,Female ,BIOS Consortium ,Genome-Wide Association Study ,Developmental Biology - Abstract
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P
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- 2019
17. Genome-wide association study identifies 30 loci associated with bipolar disorder
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Stahl, Eli A, Breen, Gerome, Forstner, Andreas J, McQuillin, Andrew, Ripke, Stephan, Trubetskoy, Vassily, Mattheisen, Manuel, Wang, Yunpeng, Coleman, Jonathan RI, Gaspar, Héléna A, de Leeuw, Christiaan A, Steinberg, Stacy, Pavlides, Jennifer M Whitehead, Trzaskowski, Maciej, Byrne, Enda M, Pers, Tune H, Holmans, Peter A, Richards, Alexander L, Abbott, Liam, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D, Anjorin, Adebayo, Antilla, Verneri, Awasthi, Swapnil, Badner, Judith A, Bækvad-Hansen, Marie, Barchas, Jack D, Bass, Nicholas, Bauer, Michael, Belliveau, Richard, Bergen, Sarah E, Pedersen, Carsten Bøcker, Bøen, Erlend, Boks, Marco P, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Bybjerg-Grauholm, Jonas, Byerley, William, Casas, Miquel, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W, Chen, Danfeng, Churchhouse, Claire, Clarke, Toni-Kim, Coryell, William, Craig, David W, Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M, Dale, Anders M, de Jong, Simone, Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Djurovic, Srdjan, Dobbyn, Amanda L, Dumont, Ashley, Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Fischer, Sascha B, Flickinger, Matthew, Foroud, Tatiana M, Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B, Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Pedersen, Marianne Giørtz, Goldstein, Jaqueline, Gordon, Scott D, Gordon-Smith, Katherine, Green, Elaine K, Green, Melissa J, Greenwood, Tiffany A, Grove, Jakob, Guan, Weihua, Guzman-Parra, José, Hamshere, Marian L, Hautzinger, Martin, Heilbronner, Urs, Herms, Stefan, Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S, and Juréus, Anders
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Male ,Bipolar Disorder ,Medical and Health Sciences ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,eQTLGen Consortium ,Depressive Disorder ,Systems Biology ,Human Genome ,Major ,Single Nucleotide ,Biological Sciences ,Serious Mental Illness ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,Brain Disorders ,Mental Health ,Psychotic Disorders ,Genetic Loci ,Case-Control Studies ,Schizophrenia ,Female ,BIOS Consortium ,Genome-Wide Association Study ,Developmental Biology - Abstract
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P
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- 2019
18. Identification of common genetic risk variants for autism spectrum disorder
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Grove, Jakob, Ripke, Stephan, Als, Thomas D, Mattheisen, Manuel, Walters, Raymond K, Won, Hyejung, Pallesen, Jonatan, Agerbo, Esben, Andreassen, Ole A, Anney, Richard, Awashti, Swapnil, Belliveau, Rich, Bettella, Francesco, Buxbaum, Joseph D, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Christensen, Jane H, Churchhouse, Claire, Dellenvall, Karin, Demontis, Ditte, De Rubeis, Silvia, Devlin, Bernie, Djurovic, Srdjan, Dumont, Ashley L, Goldstein, Jacqueline I, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Hope, Sigrun, Howrigan, Daniel P, Huang, Hailiang, Hultman, Christina M, Klei, Lambertus, Maller, Julian, Martin, Joanna, Martin, Alicia R, Moran, Jennifer L, Nyegaard, Mette, Nærland, Terje, Palmer, Duncan S, Palotie, Aarno, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, dPoterba, Timothy, Poulsen, Jesper Buchhave, Pourcain, Beate St, Qvist, Per, Rehnström, Karola, Reichenberg, Abraham, Reichert, Jennifer, Robinson, Elise B, Roeder, Kathryn, Roussos, Panos, Saemundsen, Evald, Sandin, Sven, Satterstrom, F Kyle, Davey Smith, George, Stefansson, Hreinn, Steinberg, Stacy, Stevens, Christine R, Sullivan, Patrick F, Turley, Patrick, Walters, G Bragi, Xu, Xinyi, Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium, BUPGEN, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Stefansson, Kari, Geschwind, Daniel H, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Neale, Benjamin M, Daly, Mark J, and Børglum, Anders D
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Male ,Multifactorial Inheritance ,Adolescent ,Autism Spectrum Disorder ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Denmark ,behavioral disciplines and activities ,23andMe Research Team ,Medical and Health Sciences ,Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium ,2.3 Psychological ,Risk Factors ,mental disorders ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Aetiology ,Polymorphism ,Child ,Preschool ,Pediatric ,Prevention ,Human Genome ,Single Nucleotide ,Biological Sciences ,Brain Disorders ,Mental Health ,Phenotype ,Case-Control Studies ,BUPGEN ,Female ,social and economic factors ,Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium ,Biotechnology ,Genome-Wide Association Study ,Developmental Biology - Abstract
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
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- 2019
19. Gwas Of Suicide Attempt In Psychiatric Disorders And Association With Major Depression Polygenic Risk Scores
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Mullins, Niamh, Bigdeli, Tim B., Børglum, Anders D., Coleman, Jonathan R.I., Demontis, Ditte, Mehta, Divya, Power, Robert A., Ripke, Stephan, Stahl, Eli A., Starnawska, Anna, Anjorin, Adebayo, M.R.C.Psych, Corvin, Aiden, Sanders, Alan R., Forstner, Andreas J., Reif, Andreas, Koller, Anna C., Świątkowska, Beata, Baune, Bernhard T., Müller-Myhsok, Bertram, Penninx, Brenda W.J.H., Pato, Carlos, Zai, Clement, Rujescu, Dan, Hougaard, David M., Quested, Digby, Levinson, Douglas F., Binder, Elisabeth B., Byrne, Enda M., Agerbo, Esben, Dr.Med.Sc, 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 T.R., 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, Dipl.-Psych, Weissman, Myrna M., Wray, Naomi R., Bass, Nicholas, Craddock, Nicholas, Smeland, Olav B., Andreassen, Ole A., and Mors, Ole
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- 2019
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20. Migraine polygenic risk score associates with efficacy of migraine-specific drugs
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Kogelman, Lisette JA, Esserlind, Ann-Louise, Christensen, Anne Francke, Awasthi, Swapnil, Ripke, Stephan, Ingason, Andres, Davidsson, Olafur B, Erikstrup, Christian, Hjalgrim, Henrik, Ullum, Henrik, Olesen, Jes, Hansen, Thomas Folkmann, Gudbjartsson, Daniel, Gastafsson, Omar, Stefansson, Kari, Stefansson, Hreinn, Porsteinsdottir, Unnur, Andersen, Steffen, Banasik, Karina, Brunak, Soren, Buil, Alfonso, Burgdorf, Kristoffer, Gregor, Jemec, Jennum, Poul, Nielsen, Kasper Rene, Nyegaard, Mette, Paarup, Helene Mariana, Pedersen, Ole Birger, Sorensen, Erik, Werge, Thomas, Anttila, Verneri, Artto, Ville, Belin, Andrea Carmine, de Boer, Irene, Boomsma, Dorret I, Borte, Sigrid, Chasman, Daniel I, Cherkas, Lynn, Cormand, Bru, Cuenca-Leon, Ester, Davey-Smith, George, Dichgans, Martin, van Duijn, Cornelia, Esko, Tonu, Ferrari, Michel, Frants, Rune R, Freilinger, Tobias, Furlotte, Nick, Gormley, Padhraig, Griffiths, Lyn, Hamalainen, Eija, Hiekkala, Marjo, Ikram, M Arfan, Jarvelin, Marjo-Riitta, Kajanne, Risto, Kallela, Mikko, Kaprio, Jaakko, Kaunisto, Mari, Kubisch, Christian, Kurki, Mitja, Kurth, Tobias, Launer, Lenore, Lehtimaki, Terho, Lessel, Davor, Ligthart, Lannie, Litterman, Nadia, van den Maagdenberg, Arn, Macaya, Alfons, Malik, Rainer, Mangino, Massimo, McMahon, George, Muller-Myhsok, Bertram, Neale, Benjamin M, Northover, Carrie, Nyholt, Dale R, Palotie, Aarno, Palta, Priit, Pedersen, Linda, Pedersen, Nancy, Posthuma, Danielle, Pozo-Rosich, Patricia, Pressman, Alice, Raitakari, Olli, Schurks, Markus, Sintas, Celia, Steinberg, Stacy, Strachan, David, Terwindt, Gisela, Vila-Pueyo, Marta, Wessman, Maija, Winsvold, Bendik S, Zhao, Huiying, Zwart, John-Anker, Consortium, DBDS Genomic, Consortium, Int Headache Genetics, Neurologian yksikkö, HUS Helsinki and Uusimaa Hospital District, HUS Neurocenter, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Research Programs Unit, and Aarno Palotie / Principal Investigator
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0301 basic medicine ,medicine.medical_specialty ,SUSCEPTIBILITY LOCI ,PHARMACOGENOMICS ,Triptans ,Logistic regression ,Article ,3124 Neurology and psychiatry ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,SCHIZOPHRENIA ,Medicine ,Migraine treatment ,METAANALYSIS ,Genetics (clinical) ,business.industry ,1184 Genetics, developmental biology, physiology ,3112 Neurosciences ,Area under the curve ,Odds ratio ,medicine.disease ,Confidence interval ,3. Good health ,030104 developmental biology ,Migraine ,Cohort ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ObjectiveTo assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response.MethodsWe interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome.ResultsA twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response.ConclusionsThe migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine.
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- 2019
21. Analysis of shared heritability in common disorders of the brain
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Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, and Furlotte, Nicholas
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Brain Diseases ,General Science & Technology ,Mental Disorders ,Human Genome ,Neurosciences ,Genetic Variation ,Brain Disorders ,Quantitative Trait ,Phenotype ,Rare Diseases ,Mental Health ,Risk Factors ,Clinical Research ,Neurological ,Brainstorm Consortium ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Aetiology ,Heritable ,Genome-Wide Association Study - Abstract
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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- 2018
22. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
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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, GERAD1 Consortium, CRESTAR Consortium, Collier, David A, Rujescu, Dan, Kirov, George, Owen, Michael J, O'Donovan, Michael C, and Walters, James TR
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Inheritance Patterns ,Lethal ,Medical and Health Sciences ,Gene Frequency ,Genetic ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Genetic Predisposition to Disease ,Aetiology ,Polymorphism ,Selection ,Alleles ,CRESTAR Consortium ,Human Genome ,Single Nucleotide ,Biological Sciences ,Serious Mental Illness ,GERAD1 Consortium ,Brain Disorders ,Mental Health ,Good Health and Well Being ,Genes ,Genetic Loci ,Case-Control Studies ,Schizophrenia ,Biotechnology ,Genome-Wide Association Study ,Developmental Biology - Abstract
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.
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- 2018
23. Genome-wide Association Analyses Identify 44 Risk Variants And Refine The Genetic Architecture Of Major Depression
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eQTLGen, 23andMe, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Wray, Naomi R., Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till M. F., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan F. T., Bigdeli, Tim B., Binder, Elisabeth B., Blackwood, Douglas R. H., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan I. R., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Crowley, Cheynna A., Dashti, Hassan S., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Eriksson, Nicholas, Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Giusti-Rodriguez, Paola, Goes, Fernando S., Gordon, Scott D., Grove, Jakob, Hall, Lynsey S., Hannon, Eilis, Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Hu, Ming, Hyde, Craig L., Ising, Marcus, Jansen, Rick, Jin, Fulai, Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltán, Lane, Jacqueline M., Li, Yihan, Li, Yun, Lind, Penelope A., Liu, Xiaoxiao, Lu, Leina, MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, and Weissman, Myrna M.
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- 2018
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24. Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis
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van Hulzen, Kimm JE, Scholz, Claus J, Franke, Barbara, Ripke, Stephan, Klein, Marieke, McQuillin, Andrew, Sonuga-Barke, Edmund J, PGC ADHD Working Group, Kelsoe, John R, Landén, Mikael, Andreassen, Ole A, PGC Bipolar Disorder Working Group, Lesch, Klaus-Peter, Weber, Heike, Faraone, Stephen V, Arias-Vasquez, Alejandro, and Reif, Andreas
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Pediatric ,Psychiatry ,Bipolar Disorder ,PGC ADHD Working Group ,cross-disorder meta-analysis ,Human Genome ,Psychology and Cognitive Sciences ,PGC Bipolar Disorder Working Group ,Comorbidity ,Biological Sciences ,genetic correlation ,Attention Deficit Hyperactivity Disorder (ADHD) ,Medical and Health Sciences ,Brain Disorders ,Attention-deficit/hyperactivity disorder ,Mental Health ,Good Health and Well Being ,Attention Deficit Disorder with Hyperactivity ,Genetics ,Humans ,GWAS ,2.1 Biological and endogenous factors ,genetic overlap ,Aetiology ,Genome-Wide Association Study - Abstract
BackgroundAttention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD.MethodsGenome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks.ResultsWe found a significant single nucleotide polymorphism-based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull = .64, p = 3.13 × 10-14; rGrestricted = .71, p = 4.09 × 10-16). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47 × 10-8; prs11756438 = 4.36 × 10-8) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 = 2.11 × 10-8) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue.ConclusionsThe single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.
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- 2017
25. Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations
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Van Hemert, Albert M., Porteous, David J., O'Donovan, Michael C., McIntosh, Andrew M., Lewis, Glyn, Hayward, Caroline, Traylor, Matthew, Thomson, Pippa A., Tansey, Katherine E., Smith, Daniel J., Owen, Michael J., O'Reilly, Paul F., McGuffin, Peter, Marchini, Jonathan, MacIntyre, Donald J., Kretzschmar, Warren W., Hall, Lynsey S., Gaspar, Helena A., Escott-Price, Valentina, Eley, Thalia C., Deary, Ian J., Davies, Gail, Craddock, Nick, Coleman, Jonathan R.I., Clarke, Toni-Kim, Cai, Na, Blackwood, Douglas H.R., Adams, Mark J., Rivera, Margarita, Mullins, Niamh, Lewis, Cathryn, Kan, Carol, Dehghan, Abbas, Breen, Gerome, Sullivan, Patrick F., Borglum, Anders D., Levinson, Douglas F., Werge, Thomas, Weissman, Myrna M., Volzke, Henry, Uher, Rudolf, Tiemeier, Henning, Stefansson, Kari, Smoller, Jordan W., Schulze, Thomas G., Schaefer, Catherine, Potash, James B., Trubetskoy, Vassily, Treutlein, Jens, Thorgeirsson, Thorgeir E., Thompson, Wesley, Teismann, Henning, Steinberg, Stacy, Stefansson, Hreinn, Smit, Johannes H., Sinnamon, Grant C.B., Sigurdsson, Engilbert, Shyn, Stanley I., Shi, Jianxin, Shen, Ling, Schulte, Eva C., Schoevers, Robert, Mirza, Saira Saeed, Riley, Brien P., Rice, John P., Qvist, Per, Quiroz, Jorge A., Posthuma, Danielle, Pettersson, Erik, Peterson, Roseann E., Pedersen, Marianne Giortz, Pedersen, Carsten Bocker, Painter, Jodie N., Oskarsson, Hogni, Nyholt, Dale R., Nivard, Michel G., Ng, Bernard, Mostafavi, Sara, Montgomery, Grant W., Mondimore, Francis M., Milani, Lili, Mihailov, Evelin, Middeldorp, Christel M., Mehta, Divya, Medland, Sarah E., McGrath, Patrick, Mbarek, Hamdi, Maier, Wolfgang, Maier, Robert M., MacKinnon, Dean F., Lind, Penelope A., Li, Yihan, Kutalik, Zoltan, Krogh, Jesper, Kraft, Julia, Kohane, Isaac S., Knowles, James A., Jorgenson, Eric, Jansen, Rick, Ising, Marcus, Hougaard, David M., Hottenga, Jouke-Jan, Horn, Carsten, Hoffmann, Per, Hickie, Ian B., Herms, Stefan, Hansen, Thomas F., Hansen, Christine Soholm, Grove, Jakob, Gordon, Scott D., Goes, Fernando S., Frank, Josef, Finucane, Hilary K., Kiadeh, Farnush Farhadi Hassan, Dunn, Erin C., Dolan, Conor V., Direk, Nese, Derks, Eske M., Degenhardt, Franziska, Crawford, Gregory E., Couvy-Duchesne, Baptiste, Colodro-Conde, Lucia, Christensen, Jane Hvarregaard, Castelao, Enrique, Bybjerg-Grauholm, Jonas, Buttenschon, Henriette N., Bryois, Julien, Bigdeli, Tim B., Beekman, Aartjan T.F., Bakvad-Hansen, Marie, Bacanu, Silviu-Alin, Andlauer, Till F.M., Air, Tracy M., Agerbo, Esben, Abdellaoui, Abdel, Byrne, Enda M., Mattheisen, Manuel, Ripke, Stephan, Penninx, Brenda W.J.H., Boomsma, Dorret I., Wray, Naomi R., Van Der Auwera, Sandra, Teumer, Alexander, Strohmaier, Jana, Streit, Fabian, Rietschel, Marcella, Preisig, Martin, Pistis, Giorgio, Nauck, Matthias, Homuth, Georg, Grabe, Hans J., Forstner, Andreas J., Baune, Bernhard T., Peyrot, Wouter J., Lamers, Femke, Milaneschi, Yuri, Gill, Michael, Binder, Elisabeth B., Trzaskowski, Maciej, Perlis, Roy H., Pedersen, Nancy L., Paciga, Sara A., Nothen, Markus M., Nordentoft, Merete, Muller-Myhsok, Bertram, Mortensen, Preben Bo, Mors, Ole, Metspalu, Andres, Martin, Nicholas G., Magnusson, Patrik K., Madden, Pamela A.F., Lucae, Susanne, Li, Qingqin S., Kloiber, Stefan, Kendler, Kenneth S., Heath, Andrew C., Hamilton, Steven P., Esko, Tonu, Domschke, Katharina, Domenici, Enrico, DePaulo, J. Raymond, De Geus, E.J.C., Dannlowski, Udo, Cichon, Sven, Arolt, Volker, Zhang, Futao, Yang, Jian, Xi, Hualin S., Wu, Yang, Witt, Stephanie H., Willemsen, Gonneke, Wellmann, Jurgen, Weinsheimer, Shantel Marie, Webb, Bradley T., Wang, Yunpeng, Visscher, Peter M., Viktorin, Alexander, Umbricht, Daniel, Uitterlinden, Andre G., Berger, Klaus, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Psychiatry, APH - Digital Health, Biological Psychology, Clinical Psychology, APH - Methodology, Epidemiology, Urology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Medical Informatics, and Immunology
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Netherlands Twin Register (NTR) ,Adult ,Male ,medicine.medical_specialty ,International Cooperation ,Population ,Genome-wide association study ,Overweight ,Weight Gain ,behavioral disciplines and activities ,Body Mass Index ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Internal medicine ,mental disorders ,medicine ,Journal Article ,Humans ,Genetic Predisposition to Disease ,Obesity ,Psychiatry ,education ,Problem Solving ,Depression (differential diagnoses) ,Original Investigation ,Craving ,Psychiatric Status Rating Scales ,education.field_of_study ,Depressive Disorder, Major ,Odds ratio ,medicine.disease ,030227 psychiatry ,Multicenter Study ,Diagnostic and Statistical Manual of Mental Disorders ,Psychiatry and Mental health ,C-Reactive Protein ,Cohort ,Major depressive disorder ,Female ,medicine.symptom ,Psychology ,Body mass index ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
© 2017 American Medical Association. All rights reserved.IMPORTANCE The association between major depressive disorder (MDD) and obesitymay stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. OBJECTIVE To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). DESIGN, SETTING, AND PATIENTS This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. MAIN OUTCOMES AND MEASURES Lifetime DSM-IV MDDwas diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. RESULTS Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9%male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95%CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95%CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95%CI, 1.06-1.12; P = 1.7 × 10-3). CONCLUSIONS AND RELEVANCE The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability.
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- 2017
26. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
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Goyette, Philippe, Boucher, Gabrielle, Mallon, Dermot, Ellinghaus, Eva, Jostins, Luke, Huang, Hailiang, Ripke, Stephan, Gusareva, Elena S., Annese, Vito, Hauser, Stephen L., Oksenberg, Jorge R., Thomsen, Ingo, Leslie, Stephen, Daly, Mark J., Van Steen, Kristel, Duerr, Richard H., Barrett, Jeffrey C., Mcgovern, Dermot P. B., Schumm, L. Philip, Traherne, James A., Carrington, Mary N., Kosmoliaptsis, Vasilis, Karlsen, Tom H., Franke, Andre, Rioux, John D., Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Anderson, Carl A., Andrews, Jane M., Aumais, Guy, Baidoo, Leonard, Baldassano, Robert N., Balschun, Tobias, Bampton, Peter A., Barclay, Murray, Bayless, Theodore M., Bethge, Johannes, Bis, Joshua C., Bitton, Alain, Brand, Stephan, Brant, Steven R., Buning, Carsten, Chew, Angela, Cho, Judy H., Cleynen, Isabelle, Cohain, Ariella, Croft, Anthony, D'Amato, Mauro, Danese, Silvio, De Jong, Dirk, De Vos, Martine, Denapiene, Goda, Denson, Lee A., Devaney, Kathy L., Dewit, Olivier, D'Inca, Renata, Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Essers, Jonah, Ferguson, Lynnette R., Festen, Eleonora A., Fleshner, Philip, Florin, Tim, Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jurgen, Green, Todd, Griffiths, Anne M., Guthery, Stephen L., Hakonarson, Hakon, Halfvarson, Jonas, Hanigan, Katherine, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hayward, Nicholas K., Hedl, Matija, Henderson, Paul, Xinli, Hu, Hui, Ken Y., Imielinski, Marcin, Ippoliti, Andrew, Jonaitis, Laimas, Kennedy, Nicholas A., Khan, Mohammed Azam, Kiudelis, Gediminas, Kugathasan, Subra, Kupcinskas, Limas, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lee, James C., Lees, Charlie W., Leja, Marcis, Van Limbergen, Johan, Lionetti, Paolo, Liu, Jimmy Z., Louis, Edouard, Mahy, Gillian, Mansfield, John, Massey, Dunecan, Mathew, Christopher G., Milgrom, Raquel, Mitrovic, Mitja, Montgomery, Grant, Mowat, Craig, Newman, Wwilliam, Aylwin, Ng, Siew C., Ng, Evelyn Ng, Sok Meng, Nikolaus, Susanna, Ning, Kaida, Nothen, Markus, Oikonomou, Ioannis, Palmieri, Orazio, Parkes, Miles, Phillips, Anne, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Proctor, Deborah D., Radford Smith, Graham, Rahier, Jean Francois, Raychaudhur, Soumya, Regueiro, Miguel, Rieder, Florian, Roberts, Rebecca, Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schadt, Eric E., Schreiber, Stefan, Scott, Regan, Seielstad, Mark, Sharma, Yashoda, Silverberg, Mark S., Simms, Lisa A., Skieceviciene, Jurgita, Spain, Sarah L., Steinhart, A. Hillary, Stempak, Joanne M., Stronati, Laura, Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kirstin M., Ter Velde, Anje, Theatre, Emilie, Torkvist, Leif, Tremelling, Mark, Van Der Meulen, Andrea, Van Sommeren, Suzanne, Vasiliauskas, Eric, Vermeire, Severine, Verspaget, Hein W., Walters, Thomas, Wwang, Kai, Wwang, Ming Hsi, Wweersma, Rinse K., Wei, Zhi, Whiteman, David, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhang, Hu, Zhang, Wwei, Zhao, Hongyu, Zhao, Zhen Z., Gastroenterology and Hepatology, Traherne, James [0000-0002-6003-8559], Kosmoliaptsis, Vasilis [0000-0001-7298-1387], and Apollo - University of Cambridge Repository
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Heterozygote ,Genotype ,Genotyping Techniques ,Genetic Linkage ,Ulcerative ,Human leukocyte antigen ,Biology ,Major histocompatibility complex ,Polymorphism, Single Nucleotide ,Article ,Primary sclerosing cholangitis ,Major Histocompatibility Complex ,Alleles ,Chromosome Mapping ,Colitis, Ulcerative ,Crohn Disease ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,HLA-DRB1 Chains ,Humans ,Inflammatory Bowel Diseases ,Phenotype ,Genetics ,medicine ,HLA-DR ,Polymorphism ,Colitis ,HLA-DRB1 ,Crohn's disease ,Single Nucleotide ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Immunology ,biology.protein - Abstract
Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
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- 2015
27. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depressive disorder
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Wray, Naomi R, Ripke, Stephan, Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M, Abdellaoui, Abdel, Adams, Mark J, Agerbo, Esben, Air, Tracy M, Andlauer, Till F M, Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T F, Bigdeli, Tim B, Binder, Elisabeth B, Blackwood, Douglas H R, 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, Crowley, Cheynna A, Dashti, Hassan S, Davies, Gail, Deary, Ian J, Degenhardt, Franziska, Derks, Eske M, Direk, Nese, Dolan, Conor V, Dunn, Erin C, Eley, Thalia C, Eriksson, Nicholas, Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K, Forstner, Andreas J, Frank, Josef, Gaspar, Héléna A, Gill, Michael, Giusti-Rorínguez, Paola, Goes, Fernando S, Gordon, Scott D, Grove, Jakob, Hall, Lynsey S, Hansen, Christine Søholm, Hansen, Thomas F, Herms, Stefan, Hickie, Ian B, Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M, Hu, Ming, Hyde, Craig L, Ising, Marcus, Jansen, Rick, Jin, Fulai, Jorgenson, Eric, Knowles, James A, Kohane, Isaac S, Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kutalik, Zoltan, Lane, Jacqueline M, Li, Yihan, Li, Yun, Lind, Penelope A, Liu, Xiaoxiao, Lu, Leina, MacIntyre, Donald J, MacKinnon, Dean F, Maier, Robert M, Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E, Mehta, Divya, Middeldorp, Christel M, Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M, Montgomery, Grant W, Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G, Nyholt, Dale R, O’Reilly, Paul F, Oskarsson, Hogni, Owen, Michael J, Painter, Jodie N, Bøcker, Carsten, Pedersen, Marianne Giørtz, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J, Pistis, Giorgio, Posthuma, Danielle, Purcell, Shaun M, Quiroz, Jorge A, Qvist, Per, Rice, John P, Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Saxena, Richa, Schoevers, Robert, Schulte, Eva C, Shen, Ling, Shi, Jianxin, Shyn, Stanley I, Sigurdsson, Engilbert, Sinnamon, Grant C B, Smit, Johannes H, Smith, Daniel J, Stefansson, Hreinn, Steinberg, Stacy, Stockmeier, Craig A, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E, Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa a, Thorgeirsson, Thorgeir E, Tian, Chao, Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G, Umbricht, Daniel, Auwera, Sandra Van der, Hemert, Albert M van, Viktorin, Alexander, Visscher, Peter M, Wang, Yunpeng, Webb, Bradley T., 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, EJC, DePaulo, J Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tönu, Grabe, Hans J, Hamilton, Steven P, Hayward, Caroline, Heath, Andrew C, Hinds, David A, Kendler, Kenneth S, Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S, Lucae, Susanne, Madden, Pamela AF, Magnusson, Patrik K, Martin, Nicholas G, McIntosh, Andrew M, Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, Nöthen, Markus M, O’Donovan, Michael C, Paciga, Sara A, Pedersen, Nancy L, Penninx, Brenda WJH, Perlis, Roy H, Porteous, David J, Potash, James B, Preisig, Martin, Rietschel, Marcella, Schaefer, Catherine, Schulze, Thomas G, Smoller, Jordan W, Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M, Werge, Thomas, Winslow, Ashley R, Lewis, Cathryn M, Levinson, Douglas F, Breen, Gerome, Børglum, Anders D, and Sullivan, Patrick F
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0303 health sciences ,business.industry ,Genome-wide association study ,medicine.disease ,Bioinformatics ,behavioral disciplines and activities ,Genetic architecture ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Schizophrenia ,mental disorders ,medicine ,Etiology ,Autism ,Major depressive disorder ,business ,030217 neurology & neurosurgery ,Depression (differential diagnoses) ,Anterior cingulate cortex ,030304 developmental biology - Abstract
Major depressive disorder (MDD) is a notably complex illness with a lifetime prevalence of 14%.1 It is often chronic or recurrent and is thus accompanied by considerable morbidity, excess mortality, substantial costs, and heightened risk of suicide.2-7 MDD is a major cause of disability worldwide.8 We conducted a genome-wide association (GWA) meta-analysis in 130,664 MDD cases and 330,470 controls, and identified 44 independent loci that met criteria for statistical significance. We present extensive analyses of these results which provide new insights into the nature of MDD. The genetic findings were associated with clinical features of MDD, and implicated prefrontal and anterior cingulate cortex in the pathophysiology of MDD (regions exhibiting anatomical differences between MDD cases and controls). Genes that are targets of antidepressant medications were strongly enriched for MDD association signals (P=8.5×10−10), suggesting the relevance of these findings for improved pharmacotherapy of MDD. Sets of genes involved in gene splicing and in creating isoforms were also enriched for smaller MDD GWA P-values, and these gene sets have also been implicated in schizophrenia and autism. Genetic risk for MDD was correlated with that for many adult and childhood onset psychiatric disorders. Our analyses suggested important relations of genetic risk for MDD with educational attainment, body mass, and schizophrenia: the genetic basis of lower educational attainment and higher body mass were putatively causal for MDD whereas MDD and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for MDD, and a continuous measure of risk underlies the observed clinical phenotype. MDD is not a distinct entity that neatly demarcates normalcy from pathology but rather a useful clinical construct associated with a range of adverse outcomes and the end result of a complex process of intertwined genetic and environmental effects. These findings help refine and define the fundamental basis of MDD.
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- 2017
28. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders
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Weiner, Daniel J, Wigdor, Emilie M, Ripke, Stephan, Walters, Raymond K, Kosmicki, Jack A, Grove, Jakob, Samocha, Kaitlin E, Goldstein, Jacqueline I, Okbay, Aysu, Bybjerg-Grauholm, Jonas, Werge, Thomas, Hougaard, David M, Taylor, Jacob, iPSYCH-Broad Autism Group, Psychiatric Genomics Consortium Autism Group, Skuse, David, Devlin, Bernie, Anney, Richard, Sanders, Stephan J, Bishop, Somer, Mortensen, Preben Bo, Børglum, Anders D, Smith, George Davey, Daly, Mark J, and Robinson, Elise B
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Adult ,Male ,Multifactorial Inheritance ,genetic structures ,Autism Spectrum Disorder ,Autism ,Intellectual and Developmental Disabilities (IDD) ,Intelligence ,Ethnic Groups ,behavioral disciplines and activities ,Medical and Health Sciences ,Cohort Studies ,Risk Factors ,Intellectual Disability ,mental disorders ,Genetics ,Ethnicity ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Aetiology ,Child ,Behavioral ,Genetic Association Studies ,Sequence Deletion ,Family Health ,Pediatric ,Psychiatric Genomics Consortium Autism Group ,Prevention ,Genetic Variation ,Biological Sciences ,Brain Disorders ,Phenotype ,Mental Health ,Good Health and Well Being ,Schizophrenia ,Educational Status ,Female ,iPSYCH-Broad Autism Group ,2.4 Surveillance and distribution ,Developmental Biology - Abstract
Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
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- 2017
29. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
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Marshall, Christian R, Howrigan, Daniel P, Merico, Daniele, Thiruvahindrapuram, Bhooma, Wu, Wenting, Greer, Douglas S, Antaki, Danny, Shetty, Aniket, Holmans, Peter A, Pinto, Dalila, Gujral, Madhusudan, Brandler, William M, Malhotra, Dheeraj, Wang, Zhouzhi, Fajarado, Karin V Fuentes, Maile, Michelle S, Ripke, Stephan, Agartz, Ingrid, Albus, Margot, Alexander, Madeline, Amin, Farooq, Atkins, Joshua, Bacanu, Silviu A, Belliveau, Richard A, Bergen, Sarah E, Bertalan, Marcelo, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Bulik-Sullivan, Brendan, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Cairns, Murray J, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberley D, Cheng, Wei, Cloninger, C Robert, Cohen, David, Cormican, Paul, Craddock, Nick, Crespo-Facorro, Benedicto, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farh, Kai-How, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedman, Joseph I, Forstner, Andreas J, Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Gershon, Elliot S, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I, Gratten, Jacob, de Haan, Lieuwe, Hamshere, Marian L, Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M, Henskens, Frans A, Herms, Stefan, Hirschhorn, Joel N, Hoffmann, Per, Hofman, Andrea, Huang, Hailiang, Ikeda, Masashi, and Joa, Inge
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Genetic Markers ,Male ,CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium ,Genotype ,DNA Copy Number Variations ,Medical and Health Sciences ,Clinical Research ,Risk Factors ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Aetiology ,Psychosis Endophenotypes International Consortium ,Prevention ,Human Genome ,Biological Sciences ,Serious Mental Illness ,Brain Disorders ,Mental Health ,Genetic Loci ,Case-Control Studies ,Schizophrenia ,Female ,Genome-Wide Association Study ,Biotechnology ,Developmental Biology - Abstract
Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
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- 2017
30. Local genetic effects on gene expression across 44 human tissues
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Aguet, François, Brown, Andrew A., Castel, Stephane E., Davis, Joe R., Mohammadi, Pejman, Segrè, Ayellet V., Zappala, Zachary, Abell, Nathan S., Frésard, Laure, Gamazon, Eric R., Gelfand, Ellen, Gloudemans, Michael J., He, Yuan, Hormozdiari, Farhad, Li, Xiao, Li, Xin, Liu, Boxiang, Garrido-Martín, Diego, Ongen, Halit, Palowitch, John J., Park, YoSon, Peterson, Christine B., Quon, Gerald, Ripke, Stephan, Shabalin, Andrey A., Shimko, Tyler C., Strober, Benjamin J., Sullivan, Timothy J., Teran, Nicole A., Tsang, Emily K., Zhang, Hailei, Zhou, Yi-Hui, Battle, Alexis, Bustamonte, Carlos D., Cox, Nancy J., Engelhardt, Barbara E., Eskin, Eleazar, Getz, Gad, Kellis, Manolis, Li, Gen, MacArthur, Daniel G., Nobel, Andrew B., Sabbati, Chiara, Wen, Xiaoquan, Wright, Fred A., Lappalainen, Tuuli, Ardlie, Kristin G., Dermitzakis, Emmanouil T., Brown, Christopher D., and Montgomery, Stephen B.
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Genetics ,Regulation of gene expression ,0303 health sciences ,Genomics ,Functional impact ,Computational biology ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,Expression quantitative trait loci ,Identification (biology) ,Functional genomics ,Gene ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Expression quantitative trait locus (eQTL) mapping provides a powerful means to identify functional variants influencing gene expression and disease pathogenesis. We report the identification of cis-eQTLs from 7,051 post-mortem samples representing 44 tissues and 449 individuals as part of the Genotype-Tissue Expression (GTEx) project. We find a cis-eQTL for 88% of all annotated protein-coding genes, with one-third having multiple independent effects. We identify numerous tissue-specific cis-eQTLs, highlighting the unique functional impact of regulatory variation in diverse tissues. By integrating large-scale functional genomics data and state-of-the-art fine-mapping algorithms, we identify multiple features predictive of tissue-specific and shared regulatory effects. We improve estimates of cis-eQTL sharing and effect sizes using allele specific expression across tissues. Finally, we demonstrate the utility of this large compendium of cis-eQTLs for understanding the tissue-specific etiology of complex traits, including coronary artery disease. The GTEx project provides an exceptional resource that has improved our understanding of gene regulation across tissues and the role of regulatory variation in human genetic diseases.
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- 2016
31. Publisher Correction: Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
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Pardiñas, Antonio F, Holmans, Peter, Han, Jun, Nothen, Markus, Goate, Alison, Cruchaga, Carlos, Nowotny, Petra, Morris, John C, Mayo, Kevin, Williams, Julie, Achilla, Evanthia, Agerbo, Esben, Hubbard, Leon, Barr, Cathy L, Böttger, Theresa Wimberly, Breen, Gerome, Cohen, Dan, Collier, David A, Curran, Sarah, Dempster, Emma, Dima, Danai, Sabes-Figuera, Ramon, Flanagan, Robert J, Lynham, Amy, Frangou, Sophia, Frank, Josef, Gasse, Christiane, Gaughran, Fiona, Giegling, Ina, Grove, Jakob, Hannon, Eilis, Hartmann, Annette M, Heißerer, Barbara, Helthuis, Marinka, Mantripragada, Kiran, Horsdal, Henriette Thisted, Ingimarsson, Oddur, Jollie, Karel, Kennedy, James L, Köhler, Ole, Konte, Bettina, Lang, Maren, Legge, Sophie E, Lewis, Cathryn, MacCabe, James, Rees, Elliott, Malhotra, Anil K, McCrone, Paul, Meier, Sandra M, Mill, Jonathan, Mors, Ole, Mortensen, Preben Bo, O'Donovan, Michael C, Owen, Michael J, Pedersen, Carsten B, MacCabe, James H, Rietschel, Marcella, Rujescu, Dan, Schwalber, Ameli, Sigurdsson, Engilbert, Sørensen, Holger J, Spencer, Benjamin, Stefansson, Hreinn, Støvring, Henrik, Strohmaier, Jana, Sullivan, Patrick, McCarroll, Steven A, Vassos, Evangelos, Verbelen, Moira, Walters, James T R, Werge, Thomas, Baune, Bernhard T, Byrne, Enda M, Pocklington, Andrew J, 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, Escott-Price, Valentina, Huckins, Laura M, Ruderfer, Douglas M, Santiago, Enrique, Sklar, Pamela, Stahl, Eli A, Won, Hyejung, Als, Thomas D, Andreassen, Ole A, Bækvad-Hansen, Marie, Ripke, Stephan, Pedersen, Carsten Bøcker, Børglum, Anders D, Bybjerg-Grauholm, Jonas, Djurovic, Srdjan, Durmishi, Naser, Pedersen, Marianne Giørtz, Golimbet, Vera, Hougaard, David M, Carrera, Noa, Mattheisen, Manuel, Molden, Espen, Nordentoft, Merete, Pejovic-Milovancevic, Milica, Silagadze, Teimuraz, Hansen, Christine Søholm, Stefansson, Kari, Steinberg, Stacy, Tosato, Sarah, Consortium, GERAD1, Consortium, CRESTAR, Kirov, George, Bishop, Sophie, Harold, Denise, Sims, Rebecca, Gerrish, Amy, Chapman, Jade, Abraham, Richard, Hollingworth, Paul, Pahwa, Jaspreet, Denning, Nicola, Cameron, Darren, Thomas, Charlene, Taylor, Sarah, Powell, John, Proitsi, Petroula, Lupton, Michelle, Lovestone, Simon, Passmore, Peter, Craig, David, McGuinness, Bernadette, Johnston, Janet, Hamshere, Marian L, Todd, Stephen, Maier, Wolfgang, Jessen, Frank, Heun, Reiner, Schurmann, Britta, Ramirez, Alfredo, Becker, Tim, Herold, Christine, Lacour, Andre, and Drichel, Dmitriy
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0303 health sciences ,03 medical and health sciences ,0302 clinical medicine ,ddc:570 ,Genetics ,Biology ,Humanities ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Author(s): Pardinas, 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; Baekvad-Hansen, Marie; Mortensen, Preben Bo; Pedersen, Carsten Bocker; Borglum, Anders D; Bybjerg-Grauholm, Jonas; Djurovic, Srdjan; Durmishi, Naser; Pedersen, Marianne Giortz; Golimbet, Vera; Grove, Jakob; Hougaard, David M; Mattheisen, Manuel; Molden, Espen; Mors, Ole; Nordentoft, Merete; Pejovic-Milovancevic, Milica; Sigurdsson, Engilbert; Silagadze, Teimuraz; Hansen, Christine Soholm; Stefansson, Kari; Stefansson, Hreinn; Steinberg, Stacy; Tosato, Sarah; Werge, Thomas; GERAD1 Consortium; CRESTAR Consortium; Collier, David A; Rujescu, Dan; Kirov, George; Owen, Michael J; O'Donovan, Michael C; Walters, James TR | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2019
32. Polygenic transmission and complex neuro developmental network for attention deficit hyperactivity disorder: Genome-wide association study of both common and rare variants
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Yang, Li, Neale, Benjamin M., Liu, Lu, Lee, S. Hong, Wray, Naomi R., Ji, Ning, Li, Haimei, Qian, Qiujin, Wang, Dongliang, Li, Jun, Faraone, Stephen V., Wang, Yufeng, Doyle, Alysa, Reif, Andreas, Rothenberger, Aribert, Franke, Barbara, Sonuga-Barke, Edmund J.S., Steinhausen, Hans-Christoph, Buitelaar, Jan K, Kuntsi, Jonna, Biederman, Joseph, Lesch, Klaus Peter, Kent, Lindsey, Asherson, Philip, Oades, Robert D., Loo, Sandra K., Nelson, Stanley F., Smalley, Susan L., Banaschewski, Tobias, Vasquez, Alejandro Arias, Todorov, Alexandre, Charach, A., Miranda, Ana, Warnke, Andreas, Thapar, Anita, Cormand, B., Freitag, Christine, Mick, Eric, Mulas, Fernando, Middleton, Frank, Hakonarson, Hakon, Pálmason, Haukur, Schäfer, Helmut, Roeyers, Herbert, McGough, James J., Romanos, Jasmin, Crosbie, J., Meyer, Jobst, Ramos-Qiroga, J.A., Sergeant, Joseph A, Elia, Josephine, Langely, Kate, Nisenbaum, Laura, Romanos, Marcel, Daly, Mark, Ribases, M., Gill, Michael, O’Donovan, Michael, Owen, Michael, Casas, M., Bayes, M., Lambregts-Rommelse, Nanda, Williams, Nigel, Holmans, Peter, Anney, Richard J.L., Ebstein, Richard, Schachar, R., Medland, Sarah E., Ripke, Stephan, Walitza, Susanne, Nguyen, Thuy Trang, Renner, Tobias J., Hu, Xiaolan, Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: MHeNs School for Mental Health and Neuroscience, Yang, Li, Neale, Benjamin M, Liu, Lu, Lee, S Hong, Wray, Naomi R, Ji, Ning, Li, Haimei, Qian, Qiujin, Wang, Dongliang, Li, Jun, Faraone, Stephen V, Wang, Yufeng, and Psychiatric GWAS Consortium: ADHD Subgroup
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Male ,Adolescent ,DCN MP - Plasticity and memory ,Medizin ,SNP ,Single-nucleotide polymorphism ,Genome-wide association study ,DCN PAC - Perception action and control ,Biology ,Polymorphism, Single Nucleotide ,Article ,Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3] ,Correlation ,single nucleotide polymorphisms ,Cellular and Molecular Neuroscience ,Polymorphism (computer science) ,attention-deficit hyperactivity disorder ,mental disorders ,medicine ,ddc:61 ,Humans ,ADHD ,GWAS ,Attention deficit hyperactivity disorder ,Genetic Predisposition to Disease ,DCN PAC - Perception action and control NCEBP 9 - Mental health ,ddc:610 ,Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters ,Copy-number variation ,Child ,Genetics (clinical) ,Genetics & Heredity ,Psychiatry ,Genetics ,neurodevelopment ,pathway ,Case-control study ,Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3] ,medicine.disease ,genetic architecture ,Genetic architecture ,Psychiatry and Mental health ,polygenic disorders ,Attention Deficit Disorder with Hyperactivity ,Case-Control Studies ,Female ,Genome-Wide Association Study - Abstract
Attention-deficit hyperactivity disorder (ADHD) is a complex polygenic disorder. This study aimed to discover common and rare DNA variants associated with ADHD in a large homogeneous Han Chinese ADHD case-control sample. The sample comprised 1,040 cases and 963 controls. All cases met DSM-IV ADHD diagnostic criteria. We used the Affymetrix6.0 array to assay both single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Genome-wide association analyses were performed using PLINK. SNP-heritability and SNP-genetic correlations with ADHD in Caucasians were estimated with genome-wide complex trait analysis (GCTA). Pathway analyses were performed using the Interval enRICHment Test (INRICH), the Disease Association Protein-Protein Link Evaluator (DAPPLE), and the Genomic Regions Enrichment of Annotations Tool (GREAT). We did not find genome-wide significance for single SNPs but did find an increased burden of large, rare CNVs in the ADHD sample (P=0.038). SNP-heritability was estimated to be 0.42 (standard error, 0.13, P=0.0017) and the SNP-genetic correlation with European Ancestry ADHD samples was 0.39 (SE 0.15, P=0.0072). The INRICH, DAPPLE, and GREAT analyses implicated several gene ontology cellular components, including neuron projections and synaptic components, which are consistent with a neurodevelopmental pathophysiology for ADHD. This study suggested the genetic architecture of ADHD comprises both common and rare variants. Some common causal variants are likely to be shared between Han Chinese and Caucasians. Complex neurodevelopmental networks may underlie ADHD's etiology. (c) 2013 Wiley Periodicals, Inc. Refereed/Peer-reviewed
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- 2013
33. Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection
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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, Collier, David A, Rujescu, Dan, Kirov, George, Owen, Michael J, ODonovan, Michael C, and Walters, James T R
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Genetics ,0303 health sciences ,education.field_of_study ,Candidate gene ,Mechanism (biology) ,Population ,Genome-wide association study ,Biology ,medicine.disease ,Genetic architecture ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Schizophrenia ,medicine ,education ,030217 neurology & neurosurgery ,Loss function ,ERBB4 ,030304 developmental biology - Abstract
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide such insight. We report the largest single cohort genome-wide association study of schizophrenia (11,260 cases and 24,542 controls) and through meta-analysis with existing data we identify 50 novel GWAS loci. Using gene-wide association statistics we implicate an additional set of 22 novel associations that map onto a single gene. We show for the first time that the common variant association signal is highly enriched among genes that are intolerant to loss of function mutations and that variants in these genes persist in the population despite the low fecundity associated with the disorder through the process of background selection. Associations point to novel areas of biology (e.g. metabotropic GABA-B signalling and acetyl cholinesterase), reinforce those implicated in earlier GWAS studies (e.g. calcium channel function), converge with earlier rare variants studies (e.g. NRXN1, GABAergic signalling), identify novel overlaps with autism (e.g. RBFOX1, FOXP1, FOXG1), and support early controversial candidate gene hypotheses (e.g. ERBB4 implicating neuregulin signalling). We also demonstrate the involvement of six independent central nervous system functional gene sets in schizophrenia pathophysiology. These findings provide novel insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation intolerant genes and suggest a mechanism by which common risk variants are maintained in the population.
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- 2016
34. Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers
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Stein, Murray B, Chen, Chia-Yen, Ursano, Robert J, Cai, Tianxi, Gelernter, Joel, Heeringa, Steven G, Jain, Sonia, Jensen, Kevin P, Maihofer, Adam X, Mitchell, Colter, Nievergelt, Caroline M, Nock, Matthew K, Neale, Benjamin M, Polimanti, Renato, Ripke, Stephan, Sun, Xiaoying, Thomas, Michael L, Wang, Qian, Ware, Erin B, Borja, Susan, Kessler, Ronald C, Smoller, Jordan W, and Army Study to Assess Risk and Resilience in Servicemembers (STARRS) Collaborators
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Adult ,Male ,Chromosomes ,Cohort Studies ,Young Adult ,Clinical Research ,2.3 Psychological ,Genetics ,Humans ,Psychology ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,Stress Disorders ,Other Medical and Health Sciences ,Pair 19 ,Inflammatory and immune system ,Human Genome ,Single Nucleotide ,Post-Traumatic Stress Disorder (PTSD) ,Anxiety Disorders ,Brain Disorders ,Military Personnel ,Mental Health ,Good Health and Well Being ,Genetic Loci ,Case-Control Studies ,Post-Traumatic ,Female ,Cognitive Sciences ,Pair 5 ,social and economic factors ,Carrier Proteins ,Army Study to Assess Risk and Resilience in Servicemembers (STARRS) Collaborators ,Human ,Genome-Wide Association Study - Abstract
ImportancePosttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity.ObjectiveTo discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS).Design, setting, and participantsTwo coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015.Main outcomes and measuresAssociation analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated.ResultsThe NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10-8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10-8) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10-8) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.Conclusions and relevanceIn the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.
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- 2016
35. New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis
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Lee, S Hong, Byrne, Enda M, Hultman, Christina M, Kähler, Anna, Vinkhuyzen, Anna AE, Ripke, Stephan, Andreassen, Ole A, Frisell, Thomas, Gusev, Alexander, Hu, Xinli, Karlsson, Robert, Mantzioris, Vasilis X, McGrath, John J, Mehta, Divya, Stahl, Eli A, Zhao, Qiongyi, Kendler, Kenneth S, Sullivan, Patrick F, Price, Alkes L, O'Donovan, Michael, Okada, Yukinori, Mowry, Bryan J, Raychaudhuri, Soumya, Wray, Naomi R, Schizophrenia Working Group of the Psychiatric Genomics Consortium and Rheumatoid Arthritis Consortium International, Schizophrenia Working Group of the Psychiatric Genomics Consortium Authors, Byerley, William, Cahn, Wiepke, Cantor, Rita M, Cichon, Sven, Cormican, Paul, Curtis, David, Djurovic, Srdjan, Escott-Price, Valentina, Gejman, Pablo V, Georgieva, Lyudmila, Giegling, Ina, Hansen, Thomas F, Ingason, Andrés, Kim, Yunjung, Konte, Bettina, Lee, Phil H, McIntosh, Andrew, McQuillin, Andrew, Morris, Derek W, Nöthen, Markus M, O'Dushlaine, Colm, Olincy, Ann, Olsen, Line, Pato, Carlos N, Pato, Michele T, Pickard, Benjamin S, Posthuma, Danielle, Rasmussen, Henrik B, Rietschel, Marcella, Rujescu, Dan, Schulze, Thomas G, Silverman, Jeremy M, Thirumalai, Srinivasa, Werge, Thomas, Schizophrenia Working Group of the Psychiatric Genomics Consortium Collaborators, Agartz, Ingrid, Amin, Farooq, Azevedo, Maria H, Bass, Nicholas, Black, Donald W, Blackwood, Douglas HR, Bruggeman, Richard, Buccola, Nancy G, Choudhury, Khalid, Cloninger, Robert C, Corvin, Aiden, Craddock, Nicholas, Daly, Mark J, Datta, Susmita, Donohoe, Gary J, Duan, Jubao, Dudbridge, Frank, Fanous, Ayman, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Gill, Michael, Gurling, Hugh, De Haan, Lieuwe, Hamshere, Marian L, Hartmann, Annette M, Holmans, Peter A, Kahn, René S, Keller, Matthew C, Kenny, Elaine, Kirov, George K, Krabbendam, Lydia, Krasucki, Robert, Lawrence, Jacob, Lencz, Todd, Levinson, Douglas F, Lieberman, Jeffrey A, and Lin, Dan-Yu
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Adult ,Male ,Rheumatoid Arthritis Consortium International Collaborators ,Adolescent ,Epidemiology ,Autoimmune Disease ,Cohort Studies ,Young Adult ,Clinical Research ,Rheumatoid ,Genetics ,Schizophrenia Working Group of the Psychiatric Genomics Consortium Authors ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,Arthritis ,Inflammatory and immune system ,Human Genome ,Statistics ,Genetic Variation ,Single Nucleotide ,Middle Aged ,Schizophrenia Working Group of the Psychiatric Genomics Consortium Collaborators ,Serious Mental Illness ,Brain Disorders ,Rheumatoid Arthritis Consortium International Authors ,Cross-Sectional Studies ,Mental Health ,Schizophrenia Working Group of the Psychiatric Genomics Consortium and Rheumatoid Arthritis Consortium International ,Schizophrenia ,Public Health and Health Services ,Female ,Gene-Environment Interaction ,Genome-Wide Association Study - Abstract
BackgroundA long-standing epidemiological puzzle is the reduced rate of rheumatoid arthritis (RA) in those with schizophrenia (SZ) and vice versa. Traditional epidemiological approaches to determine if this negative association is underpinned by genetic factors would test for reduced rates of one disorder in relatives of the other, but sufficiently powered data sets are difficult to achieve. The genomics era presents an alternative paradigm for investigating the genetic relationship between two uncommon disorders.MethodsWe use genome-wide common single nucleotide polymorphism (SNP) data from independently collected SZ and RA case-control cohorts to estimate the SNP correlation between the disorders. We test a genotype X environment (GxE) hypothesis for SZ with environment defined as winter- vs summer-born.ResultsWe estimate a small but significant negative SNP-genetic correlation between SZ and RA (-0.046, s.e. 0.026, P = 0.036). The negative correlation was stronger for the SNP set attributed to coding or regulatory regions (-0.174, s.e. 0.071, P = 0.0075). Our analyses led us to hypothesize a gene-environment interaction for SZ in the form of immune challenge. We used month of birth as a proxy for environmental immune challenge and estimated the genetic correlation between winter-born and non-winter born SZ to be significantly less than 1 for coding/regulatory region SNPs (0.56, s.e. 0.14, P = 0.00090).ConclusionsOur results are consistent with epidemiological observations of a negative relationship between SZ and RA reflecting, at least in part, genetic factors. Results of the month of birth analysis are consistent with pleiotropic effects of genetic variants dependent on environmental context.
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- 2015
36. Joint Analysis Of Psychiatric Disorders Increases Accuracy Of Risk Prediction For Schizophrenia, Bipolar Disorder, And Major Depressive Disorder
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Maier, Robert, Moser, Gerhard, Chen, Guo-Bo, Ripke, Stephan, Coryell, William, Potash, James B., Scheftner, William A., Shi, Jianxin, Weissman, Myrna M., Hultman, Christina M., Landén, Mikael, Levinson, Douglas F., Kendler, Kenneth S., Smoller, Jordan W., Wray, Naomi R., Lee, S. Hong, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A., Anjorin, Adebayo, Anney, Richard, Arking, Dan E., Asherson, Philip, Azevedo, Maria H., Backlund, Lena, Badner, Judith A., Bailey, Anthony J., Banaschewski, Tobias, Barchas, Jack D., Barnes, Michael R., Barrett, Thomas B., Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah E., Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B., Black, Donald W., Blackwood, Douglas H.R., Bloss, Cinnamon S., Boehnke, Michael, Boomsma, Dorret I., Breen, Gerome, Breuer, René, Bruggeman, Richard, Buccola, Nancy G., Buitelaar, Jan K., Bunney, William E., Buxbaum, Joseph D., Byerley, William F., Caesar, Sian, Cahn, Wiepke, Cantor, Rita M., Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C. Robert, Collier, David A., Cook, Edwin H., Coon, Hilary, Cormand, Bru, Cormican, Paul, Corvin, Aiden, Coryell, William H., Craddock, Nicholas, Craig, David W., Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L., Curtis, David, Czamara, Darina, Daly, Mark J., Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J., Degenhardt, Franziska, Devlin, Bernie, Djurovic, Srdjan, Donohoe, Gary J., Doyle, Alysa E., Duan, Jubao, and Dudbridge, Frank
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- 2015
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37. Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7
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Foroud, Tatiana, Lai, Dongbing, Koller, Daniel, Van't Hof, Femke, Kurki, Mitja I, Anderson, Craig S, Brown, Robert D, Connolly, Edward Sander, Eriksson, Johan G, Flaherty, Matthew, Fornage, Myriam, von Und Zu Fraunberg, Mikael, Gaál, Emília I, Laakso, Aki, Hernesniemi, Juha, Huston, John, Jääskeläinen, Juha E, Kiemeney, Lambertus A, Kivisaari, Riku, Kleindorfer, Dawn, Ko, Nerissa, Lehto, Hanna, Mackey, Jason, Meissner, Irene, Moomaw, Charles J, Mosley, Thomas H, Moskala, Marek, Niemelä, Mika, Palotie, Aarno, Pera, Joanna, Rinkel, Gabriel, Ripke, Stephan, Rouleau, Guy, Ruigrok, Ynte, Sauerbeck, Laura, Słowik, Agnieszka, Vermeulen, Sita H, Woo, Daniel, Worrall, Bradford B, Broderick, Joseph, and Familial Intracranial Aneurysm Study Investigators
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Adult ,Male ,chromosomes ,pair 7 ,Clinical Sciences ,Cardiorespiratory Medicine and Haematology ,White People ,Cohort Studies ,Genetics ,Humans ,2.1 Biological and endogenous factors ,human ,Polymorphism ,Aetiology ,Aged ,genome-wide association study ,Neurology & Neurosurgery ,Whites ,Familial Intracranial Aneurysm Study Investigators ,Human Genome ,Neurosciences ,Intracranial Aneurysm ,Single Nucleotide ,Middle Aged ,Brain Disorders ,Stroke ,Female ,Biotechnology - Abstract
Background and purposeCommon variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk.MethodsInitial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest.ResultsGenome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P
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- 2014
38. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases
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Gusev, Alexander, Lee, S Hong, Trynka, Gosia, Finucane, Hilary, Vilhjálmsson, Bjarni J, Xu, Han, Zang, Chongzhi, Ripke, Stephan, Bulik-Sullivan, Brendan, Stahl, Eli, Schizophrenia Working Group of the Psychiatric Genomics Consortium, SWE-SCZ Consortium, Kähler, Anna K, Hultman, Christina M, Purcell, Shaun M, McCarroll, Steven A, Daly, Mark, Pasaniuc, Bogdan, Sullivan, Patrick F, Neale, Benjamin M, Wray, Naomi R, Raychaudhuri, Soumya, and Price, Alkes L
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Genetics & Heredity ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Prevention ,Human Genome ,Inheritance Patterns ,Genetic Variation ,Biological Sciences ,Regulatory Elements ,Medical and Health Sciences ,Open Reading Frames ,Inborn ,Genetic ,Genetic Diseases ,Models ,SWE-SCZ Consortium ,Genetics ,Humans ,Computer Simulation ,Transcriptional ,Genome-Wide Association Study - Abstract
Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of hg(2) from imputed SNPs (5.1× enrichment; p = 3.7× 10(-17)) and 38% (SE = 4%) of hg(2) from genotyped SNPs (1.6× enrichment, p = 1.0× 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained
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- 2014
39. Polygenic dissection of diagnosis and clinical dimensions of bipolar disorder and schizophrenia
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Ruderfer, Douglas M, Fanous, Ayman H, Ripke, Stephan, McQuillin, Andrew, Amdur, Richard L, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Cross-Disorder Working Group of the Psychiatric Genomics Consortium, Gejman, Pablo V, O'Donovan, Michael C, Andreassen, Ole A, Djurovic, Srdjan, Hultman, Christina M, Kelsoe, John R, Jamain, Stephane, Landén, Mikael, Leboyer, Marion, Nimgaonkar, Vishwajit, Nurnberger, John, Smoller, Jordan W, Craddock, Nick, Corvin, Aiden, Sullivan, Patrick F, Holmans, Peter, Sklar, Pamela, and Kendler, Kenneth S
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Bipolar Disorder ,Cell Cycle Proteins ,polygenic ,Medical and Health Sciences ,Phosphatidylinositol 3-Kinases ,Odds Ratio ,Genetics ,Humans ,2.1 Biological and endogenous factors ,cross disorder ,Genetic Predisposition to Disease ,Polymorphism ,Aetiology ,clinical symptoms ,Psychiatry ,Schizophrenia Working Group of the Psychiatric Genomics Consortium ,Cross-Disorder Working Group of the Psychiatric Genomics Consortium ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Nuclear Proteins ,Single Nucleotide ,Statistical ,Biological Sciences ,Serious Mental Illness ,Bipolar Disorder Working Group of the Psychiatric Genomics Consortium ,L-Type ,bipolar ,Brain Disorders ,schizophrenia ,Phenotype ,Mental Health ,Case-Control Studies ,Schizophrenic Psychology ,Calcium Channels ,Factor Analysis ,Genome-Wide Association Study - Abstract
Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically.
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- 2014
40. No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis
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Goris, An, van Setten, Jessica, Diekstra, Frank, Ripke, Stephan, Patsopoulos, Nikolaos A, Sawcer, Stephen J, International Multiple Sclerosis Genetics Consortium, van Es, Michael, Australia and New Zealand MS Genetics Consortium, Andersen, Peter M, Melki, Judith, Meininger, Vincent, Hardiman, Orla, Landers, John E, Brown, Robert H, Shatunov, Aleksey, Leigh, Nigel, Al-Chalabi, Ammar, Shaw, Christopher E, Traynor, Bryan J, Chiò, Adriano, Restagno, Gabriella, Mora, Gabriele, Ophoff, Roel A, Oksenberg, Jorge R, Van Damme, Philip, Compston, Alastair, Robberecht, Wim, Dubois, Bénédicte, van den Berg, Leonard H, De Jager, Philip L, Veldink, Jan H, and de Bakker, Paul IW
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Genetics & Heredity ,Multiple Sclerosis ,Amyotrophic Lateral Sclerosis ,Human Genome ,Neurosciences ,Comorbidity ,Single Nucleotide ,Neurodegenerative ,Biological Sciences ,Autoimmune Disease ,Medical and Health Sciences ,International Multiple Sclerosis Genetics Consortium ,Brain Disorders ,Rare Diseases ,Clinical Research ,Neurological ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Genetic Predisposition to Disease ,Australia and New Zealand MS Genetics Consortium ,Polymorphism ,ALS ,Aetiology - Abstract
Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.
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- 2014
41. Genome-wide association analysis identifies 13 new risk loci for schizophrenia
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Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Kähler, Anna K, Akterin, Susanne, Bergen, Sarah E, Collins, Ann L, Crowley, James J, Fromer, Menachem, Kim, Yunjung, Lee, Sang Hong, Magnusson, Patrik KE, Sanchez, Nick, Stahl, Eli A, Williams, Stephanie, Wray, Naomi R, Xia, Kai, Bettella, Francesco, Borglum, Anders D, Bulik-Sullivan, Brendan K, Cormican, Paul, Craddock, Nick, de Leeuw, Christiaan, Durmishi, Naser, Gill, Michael, Golimbet, Vera, Hamshere, Marian L, Holmans, Peter, Hougaard, David M, Kendler, Kenneth S, Lin, Kuang, Morris, Derek W, Mors, Ole, Mortensen, Preben B, Neale, Benjamin M, O'Neill, Francis A, Owen, Michael J, Milovancevic, Milica Pejovic, Posthuma, Danielle, Powell, John, Richards, Alexander L, Riley, Brien P, Ruderfer, Douglas, Rujescu, Dan, Sigurdsson, Engilbert, Silagadze, Teimuraz, Smit, August B, Stefansson, Hreinn, Steinberg, Stacy, Suvisaari, Jaana, Tosato, Sarah, Verhage, Matthijs, Walters, James T, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Douglas F, Gejman, Pablo V, Laurent, Claudine, Mowry, Bryan J, O'Donovan, Michael C, Pulver, Ann E, Schwab, Sibylle G, Wildenauer, Dieter B, Dudbridge, Frank, Shi, Jianxin, Albus, Margot, Alexander, Madeline, Campion, Dominique, Cohen, David, Dikeos, Dimitris, Duan, Jubao, Eichhammer, Peter, Godard, Stephanie, Hansen, Mark, Lerer, F Bernard, Liang, Kung-Yee, Maier, Wolfgang, Mallet, Jacques, Nertney, Deborah A, Nestadt, Gerald, Norton, Nadine, Papadimitriou, George N, Ribble, Robert, Sanders, Alan R, Silverman, Jeremy M, Walsh, Dermot, Williams, Nigel M, Wormley, Brandon, Psychosis Endophenotypes International Consortium, Arranz, Maria J, Bakker, Steven, Bender, Stephan, Bramon, Elvira, and Collier, David
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Sweden ,Male ,Wellcome Trust Case Control Consortium 2 ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Case-Control Studies ,Schizophrenia ,Multicenter Genetic Studies of Schizophrenia Consortium ,Humans ,Mental health ,Genetic Predisposition to Disease ,Female ,Polymorphism ,Psychosis Endophenotypes International Consortium ,Genome-Wide Association Study ,Developmental Biology - Abstract
Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.
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- 2013
42. Rare complete knockouts in humans: population distribution and significant role in autism spectrum disorders
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Lim, Elaine T, Raychaudhuri, Soumya, Sanders, Stephan J, Stevens, Christine, Sabo, Aniko, MacArthur, Daniel G, Neale, Benjamin M, Kirby, Andrew, Ruderfer, Douglas M, Fromer, Menachem, Lek, Monkol, Liu, Li, Flannick, Jason, Ripke, Stephan, Nagaswamy, Uma, Muzny, Donna, Reid, Jeffrey G, Hawes, Alicia, Newsham, Irene, Wu, Yuanqing, Lewis, Lora, Dinh, Huyen, Gross, Shannon, Wang, Li-San, Lin, Chiao-Feng, Valladares, Otto, Gabriel, Stacey B, dePristo, Mark, Altshuler, David M, Purcell, Shaun M, NHLBI Exome Sequencing Project, State, Matthew W, Boerwinkle, Eric, Buxbaum, Joseph D, Cook, Edwin H, Gibbs, Richard A, Schellenberg, Gerard D, Sutcliffe, James S, Devlin, Bernie, Roeder, Kathryn, and Daly, Mark J
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Male ,Child Development Disorders ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Loss of Heterozygosity ,Chromosomes ,Linkage Disequilibrium ,Risk Factors ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Psychology ,NHLBI Exome Sequencing Project ,Aetiology ,Child ,Preschool ,Pervasive ,Demography ,Pediatric ,Neurology & Neurosurgery ,Homozygote ,Human Genome ,Neurosciences ,Genetic Variation ,Brain Disorders ,Mental Health ,Case-Control Studies ,Female ,Cognitive Sciences ,Gene Deletion ,Human - Abstract
To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (≤ 5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudoautosomal regions on the X chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together, these results provide compelling evidence that rare autosomal and X chromosome complete gene knockouts are important inherited risk factors for ASD.
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- 2013
43. Genome-wide association study of clinical dimensions of schizophrenia: polygenic effect on disorganized symptoms
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Fanous, Ayman H, Zhou, Baiyu, Aggen, Steven H, Bergen, Sarah E, Amdur, Richard L, Duan, Jubao, Sanders, Alan R, Shi, Jianxin, Mowry, Bryan J, Olincy, Ann, Amin, Farooq, Cloninger, C Robert, Silverman, Jeremy M, Buccola, Nancy G, Byerley, William F, Black, Donald W, Freedman, Robert, Dudbridge, Frank, Holmans, Peter A, Ripke, Stephan, Gejman, Pablo V, Kendler, Kenneth S, Levinson, Douglas F, and Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium
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Male ,Multifactorial Inheritance ,Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium ,Medical and Health Sciences ,Linkage Disequilibrium ,Clinical Research ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Polymorphism ,Aetiology ,Psychiatric Status Rating Scales ,Psychiatry ,Prevention ,Human Genome ,Psychology and Cognitive Sciences ,Single Nucleotide ,Statistical ,Serious Mental Illness ,Brain Disorders ,Mental Health ,Good Health and Well Being ,Case-Control Studies ,Schizophrenia ,Schizophrenic Psychology ,Female ,Factor Analysis ,Genome-Wide Association Study ,Biotechnology - Abstract
ObjectiveMultiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia.MethodBased on the Lifetime Dimensions of Psychosis Scale ratings of 2,454 case subjects of European ancestry from the Molecular Genetics of Schizophrenia (MGS) sample, three symptom factors (positive, negative/disorganized, and mood) were identified with exploratory factor analysis. Quantitative scores for each factor from a confirmatory factor analysis were analyzed for association with 696,491 single-nucleotide polymorphisms (SNPs) using linear regression, with correction for age, sex, clinical site, and ancestry. Polygenic score analysis was carried out to determine whether case and comparison subjects in 16 Psychiatric GWAS Consortium (PGC) schizophrenia samples (excluding MGS samples) differed in scores computed by weighting their genotypes by MGS association test results for each symptom factor.ResultsNo genome-wide significant associations were observed between SNPs and factor scores. Most of the SNPs producing the strongest evidence for association were in or near genes involved in neurodevelopment, neuroprotection, or neurotransmission, including genes playing a role in Mendelian CNS diseases, but no statistically significant effect was observed for any defined gene pathway. Finally, polygenic scores based on MGS GWAS results for the negative/disorganized factor were significantly different between case and comparison subjects in the PGC data set; for MGS subjects, negative/disorganized factor scores were correlated with polygenic scores generated using case-control GWAS results from the other PGC samples.ConclusionsThe polygenic signal that has been observed in cross-sample analyses of schizophrenia GWAS data sets could be in part related to genetic effects on negative and disorganized symptoms (i.e., core features of chronic schizophrenia).
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- 2012
44. Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans
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McLaren, Paul J, Ripke, Stephan, Pelak, Kimberly, Weintrob, Amy C, Patsopoulos, Nikolaos A, Jia, Xiaoming, Erlich, Rachel L, Lennon, Niall J, Kadie, Carl M, Heckerman, David, Gupta, Namrata, Haas, David W, Deeks, Steven G, Pereyra, Florencia, Walker, Bruce D, de Bakker, Paul IW, and International HIV Controllers Study
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African Americans ,Genetics & Heredity ,International HIV Controllers Study ,Genetic Variation ,HIV Infections ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Black or African American ,Infectious Diseases ,HLA-B Antigens ,HLA Antigens ,HIV-1 ,Genetics ,Humans ,HIV/AIDS ,2.1 Biological and endogenous factors ,Polymorphism ,Aetiology ,Infection ,Disease Resistance - Abstract
A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n = 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B*57:03 [odds ratio (OR) = 5.1; P= 3.4 × 10(-18)] and B*81:01 (OR = 4.8; P= 1.3 × 10(-9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P = 1.2 × 10(-21)) and explains the signal of several HLA-B alleles, including B*57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P= 2.8 × 10(-15)) in the canonical F pocket, position 63 in the B pocket (P= 1.5 × 10(-3)) and the non-pocket position 245 (P= 8.8 × 10(-10)), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control.
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- 2012
45. Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis
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Xie, Gang, Roshandel, Delnaz, Sherva, Richard, Monach, Paul A., Lu, Emily Yue, Kung, Tabitha, Carrington, Keisha, Zhang, Steven S., Pulit, Sara L., Ripke, Stephan, Carette, Simon, Dellaripa, Paul F., Edberg, Jeffrey C., Hoffman, Gary S., Khalidi, Nader, Langford, Carol A., Mahr, Alfred D., St.Clair, E. William, Seo, Philip, Specks, Ulrich, Spiera, Robert F., Stone, John H., Ytterberg, Steven R., Raychaudhuri, Soumya, de Bakker, Paul I. W., Farrer, Lindsay A., Amos, Christopher I., Merkel, Peter A., and Siminovitch, Katherine A.
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Adult ,Male ,Genotype ,Granulomatosis with Polyangiitis ,Semaphorins ,Polymorphism, Single Nucleotide ,Article ,Major Histocompatibility Complex ,Gene Frequency ,Haplotypes ,Humans ,Female ,Genetic Predisposition to Disease ,Alleles ,Genetic Association Studies ,HLA-DP beta-Chains ,Genome-Wide Association Study - Abstract
To identify genetic determinants of granulomatosis with polyangiitis (Wegener's) (GPA).We carried out a genome-wide association study (GWAS) of 492 GPA cases and 1,506 healthy controls (white subjects of European descent), followed by replication analysis of the most strongly associated signals in an independent cohort of 528 GPA cases and 1,228 controls.Genome-wide significant associations were identified in 32 single-nucleotide polymorphic (SNP) markers across the HLA region, the majority of which were located in the HLA-DPB1 and HLA-DPA1 genes encoding the class II major histocompatibility complex (MHC) DPβ chain 1 and DPα chain 1 proteins, respectively. Peak association signals in these 2 genes, emanating from SNPs rs9277554 (for DPβ chain 1) and rs9277341 (DPα chain 1) were strongly replicated in an independent cohort (in the combined analysis of the initial cohort and the replication cohort, P = 1.92 × 10(-50) and 2.18 × 10(-39) , respectively). Imputation of classic HLA alleles and conditional analyses revealed that the SNP association signal was fully accounted for by the classic HLA-DPB1*04 allele. An independent single SNP, rs26595, near SEMA6A (the gene for semaphorin 6A) on chromosome 5, was also associated with GPA, reaching genome-wide significance in a combined analysis of the GWAS and replication cohorts (P = 2.09 × 10(-8) ).We identified the SEMA6A and HLA-DP loci as significant contributors to risk for GPA, with the HLA-DPB1*04 allele almost completely accounting for the MHC association. These two associations confirm the critical role of immunogenetic factors in the development of GPA.
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- 2012
46. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
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Jostins, Luke, Ripke, Stephan, Weersma, Rinse K., Duerr, Richard H., Mcgovern, Dermot P., Hui, Ken Y., Lee, James C., Philip Schumm, L., Sharma, Yashoda, Anderson, Carl A., Essers, Jonah, Mitrovic, Mitja, Ning, Kaida, Cleynen, Isabelle, Theatre, Emilie, Spain, Sarah L., Raychaudhuri, Soumya, Goyette, Philippe, Wei, Zhi, Abraham, Clara, Achkar, Jean Paul, Ahmad, Tariq, Amininejad, Leila, Ananthakrishnan, Ashwin N., Andersen, Vibeke, Andrews, Jane M., Baidoo, Leonard, Balschun, Tobias, Bampton, Peter A., Bitton, Alain, Boucher, Gabrielle, Brand, Stephan, Büning, Carsten, Cohain, Ariella, Cichon, Sven, D'Amato, Mauro, De Jong, Dirk, Devaney, Kathy L., Dubinsky, Marla, Edwards, Cathryn, Ellinghaus, David, Ferguson, Lynnette R., Franchimont, Denis, Fransen, Karin, Gearry, Richard, Georges, Michel, Gieger, Christian, Glas, Jürgen, Haritunians, Talin, Hart, Ailsa, Hawkey, Chris, Hedl, Matija, Xinli, Hu, Karlsen, Tom H., Kupcinskas, Limas, Kugathasan, Subra, Latiano, Anna, Laukens, Debby, Lawrance, Ian C., Lees, Charlie W., Louis, Edouard, Mahy, Gillian, Mansfield, John, Morgan, Angharad R., Mowat, Craig, Newman, William, Palmieri, Orazio, Ponsioen, Cyriel Y., Potocnik, Uros, Prescott, Natalie J., Regueiro, Miguel, Rotter, Jerome I., Russell, Richard K., Sanderson, Jeremy D., Sans, Miquel, Satsangi, Jack, Schreiber, Stefan, Simms, Lisa A., Sventoraityte, Jurgita, Targan, Stephan R., Taylor, Kent D., Tremelling, Mark, Verspaget, Hein W., De Vos, Martine, Wijmenga, Cisca, Wilson, David C., Winkelmann, Juliane, Xavier, Ramnik J., Zeissig, Sebastian, Zhang, Bin, Zhang, Clarence K., Zhao, Hongyu, Silverberg, Mark S., Annese, Vito, Hakonarson, Hakon, Brant, Steven R., Radford Smith, Graham, Mathew, Christopher G., Rioux, John D., Schadt, Eric E., Daly, Mark J., Franke, Andre, Parkes, Miles, Vermeire, Severine, Barrett, Jeffrey C., Cho, Judy H., Barclay, M, Peyrin Biroulet, L, Chamaillard, M, Colombel, Jf, Cottone, M, Croft, A, D'Incà, R, Halfvarson J, Hanigan K, Henderson, P, Hugot, Jp, Karban, A, Kennedy, Na, Khan, Ma, Lémann, M, Levine, A, Massey, D, Milla, M, Montgomery, Gw, Ng, Sm, Oikonomou, I, Peeters, H, Proctor, Dd, Rahier, Jf, Roberts, R, Rutgeerts, P, Seibold, F, Stronati, Laura, Taylor, Km, Törkvist, L, Ublick, K, Van Limbergen, J, Van Gossum, A, Vatn, Mh, Zhang, H, Zhang, W, Andrews, Jm, Bampton, Pa, Florin, Th, Gearry, R, Krishnaprasad, K, Lawrance, Ic, Mahy, G, Radford Smith, G, Roberts, Rl, Simms, La, Amininijad, L, Cleynen, I, Dewit, O, Franchimont, D, Georges, M, Laukens, D, Theatre, E, Vermeire, S, Aumais, G, Baidoo, L, Barrie AM 3rd, Beck, K, Bernard, Ej, Binion, Dg, Bitton, A, Brant, Sr, Cho, Jh, Cohen, A, Croitoru, K, Daly, Mj, Datta, Lw, Deslandres, C, Duerr, Rh, Dutridge, D, Ferguson, J, Fultz, J, Goyette, P, Greenberg, Gr, Haritunians, T, Jobin, G, Katz, S, Lahaie, Rg, Mcgovern, Dp, Nelson, L, Ning, K, Paré, P, Regueiro, Md, Rioux, Jd, Ruggiero, E, Schumm, L, Schwartz, M, Scott, R, Sharma, Y, Silverberg, Ms, Spears, D, Steinhart, A, Stempak, Jm, Swoger, Jm, Tsagarelis, C, Zhang, C, Zhao, H, Aerts, J, Ahmad, T, Arbury, H, Attwood, A, Auton, A, Ball, Sg, Balmforth, Aj, Barnes, C, Barrett, Jc, Barroso, I, Barton, A, Bennett, Aj, Bhaskar, S, Blaszczyk, K, Bowes, J, Brand, Oj, Braund, Ps, Bredin, F, Breen, G, Brown, Mj, Bruce, In, Bull, J, Burren, Os, Burton, J, Byrnes, J, Caesar, S, Cardin, N, Clee, Cm, Coffey, Aj, Connell, Jm, Conrad, Df, Cooper, Jd, Dominiczak, Af, Downes, K, Drummond, He, Dudakia, D, Dunham, A, Ebbs, B, Eccles, D, Edkins, S, Edwards, C, Elliot, A, Emery, P, Evans, Dm, Evans, G, Eyre, S, Farmer, A, Ferrier, In, Flynn, E, Forbes, A, Forty, L, Franklyn, Ja, Frayling, Tm, Freathy, Rm, Giannoulatou, E, Gibbs, P, Gilbert, P, Gordon Smith, K, Gray, E, Green, E, Groves, Cj, Grozeva, D, Gwilliam, R, Hall, A, Hammond, N, Hardy, M, Harrison, P, Hassanali, N, Hebaishi, H, Hines, S, Hinks, A, Hitman, Ga, Hocking, L, Holmes, C, Howard, E, Howard, P, Howson, Jm, Hughes, D, Hunt, S, Isaacs, Jd, Jain, M, Jewell, Dp, Johnson, T, Jolley, Jd, Jones, Ir, Jones, La, Kirov, G, Langford, Cf, Lango Allen, H, Lathrop, Gm, Lee, J, Lee, Kl, Lees, C, Lewis, K, Lindgren, Cm, Maisuria Armer, M, Maller, J, Mansfield, J, Marchini, Jl, Martin, P, Massey, Dc, Mcardle, Wl, Mcguffin, P, Mclay, Ke, Mcvean, G, Mentzer, A, Mimmack, Ml, Morgan, Ae, Morris, Ap, Mowat, C, Munroe, Pb, Myers, S, Newman, W, Nimmo, Er, O'Donovan, Mc, Onipinla, A, Ovington, Nr, Owen, Mj, Palin, K, Palotie, A, Parnell, K, Pearson, R, Pernet, D, Perry, Jr, Phillips, A, Plagnol, V, Prescott, Nj, Prokopenko, I, Quail, Ma, Rafelt, S, Rayner, Nw, Reid, Dm, Renwick, A, Ring, Sm, Robertson, N, Robson, S, Russell, E, St Clair, D, Sambrook, Jg, Sanderson, Jd, Sawcer, Sj, Schuilenburg, H, Scott, Ce, Seal, S, Shaw Hawkins, S, Shields, Bm, Simmonds, Mj, Smyth, Dj, Somaskantharajah, E, Spanova, K, Steer, S, Stephens, J, Stevens, He, Stirrups, K, Stone, Ma, Strachan, Dp, Su, Z, Symmons, Dp, Thompson, Jr, Thomson, W, Tobin, Md, Travers, Me, Turnbull, C, Vukcevic, D, Wain, Lv, Walker, M, Walker, Nm, Wallace, C, Warren Perry, M, Watkins, Na, Webster, J, Weedon, Mn, Wilson, Ag, Woodburn, M, Wordsworth, Bp, Yau, C, Young, Ah, Zeggini, E, Brown, Ma, Burton, Pr, Caulfield, Mj, Compston, A, Farrall, M, Gough, Sc, Hall, As, Hattersley, At, Hill, Av, Mathew, Cg, Pembrey, M, Satsangi, J, Stratton, Mr, Worthington, J, Hurles, Me, Duncanson, A, Ouwehand, Wh, Parkes, M, Rahman, N, Todd, Ja, Samani, Nj, Kwiatkowski, Dp, Mccarthy, Mi, Craddock, N, Deloukas, P, Donnelly, P, Blackwell, Jm, Bramon, E, Casas, Jp, Corvin, A, Jankowski, J, Markus, Hs, Palmer, Cn, Plomin, R, Rautanen, A, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Pirinen, M, Strange, A, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
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Genome-wide association study ,Disease ,SUSCEPTIBILITY ,Inflammatory bowel disease ,NUMBER ,0302 clinical medicine ,Crohn Disease ,NETWORK ,Genetics ,0303 health sciences ,Multidisciplinary ,Genomics ,Ulcerative colitis ,3. Good health ,Colitis, Ulcerative ,Genetic Predisposition to Disease ,Genome, Human ,Haplotypes ,Humans ,Inflammatory Bowel Diseases ,Mycobacterium ,Mycobacterium Infections ,Mycobacterium tuberculosis ,Phenotype ,Polymorphism, Single Nucleotide ,Reproducibility of Results ,Genome-Wide Association Study ,Host-Pathogen Interactions ,IRGM ,Medical genetics ,030211 gastroenterology & hepatology ,EXPRESSION ,medicine.medical_specialty ,Immunology ,Biology ,Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2] ,TUBERCULOSIS ,03 medical and health sciences ,Medical research ,medicine ,Allele ,METAANALYSIS ,030304 developmental biology ,HYPER-IGE SYNDROME ,MUTATIONS ,medicine.disease ,RISK LOCI ,Genetic architecture ,digestive system diseases - Abstract
Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations(1). Genome-wide association studies and subsequent meta-analyses of these two diseases(2,3) as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy(4), in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases(5). Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.
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- 2012
47. P-194 YI A Model Integrating Genetic and Environmental Factors Can Differentiate Crohnʼs Disease from Ulcerative Colitis
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Fiocchi Claudio, Wang Ming-Hsi, Rebert Nancy, Achkar Jean Paul, Duerr Richard, and Ripke Stephan
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medicine.medical_specialty ,business.industry ,Internal medicine ,Gastroenterology ,medicine ,Immunology and Allergy ,Disease ,medicine.disease ,business ,Ulcerative colitis - Published
- 2014
48. Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia
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Anney, Richard J. L., Ripke, Stephan, Anttila, Verneri, Grove, Jakob, Holmans, Peter, Huang, Hailiang, Klei, Lambertus, Lee, Phil H., Medland, Sarah E., and Neale, Benjam
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Heritability ,Genome-wide association study ,Meta-analysis ,Genetic correlation ,mental disorders ,Neurodevelopment ,Schizophrenia ,Autism spectrum disorder ,Gene-set analysis ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit ,3. Good health - Abstract
Background Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR)
49. Mapping the human genetic architecture of COVID-19
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Niemi, Mari E. K., Karjalainen, Juha, Liao, Rachel G., Daly, Mark, Ganna, Andrea, Pathak, Gita A., Andrews, Shea J., Kanai, Masahiro, Veerapen, Kumar, Fernandez-Cadenas, Israel, Schulte, Eva C., Striano, Pasquale, Marttila, Minttu, Minica, Camelia, Marouli, Eirini, Karim, Mohd Anisul, Wendt, Frank R., Savage, Jeanne, Sloofman, Laura, Butler-Laporte, Guillaume, Kim, Han-Na, Kanoni, Stavroula, Okada, Yukinori, Byun, Jinyoung, Han, Younghun, Uddin, Mohammed Jashim, Smith, George Davey, Willer, Cristen J., Buxbaum, Joseph D., Mehtonen, Juha, Finucane, Hilary, Cordioli, Mattia, Martin, Alicia R., Zhou, Wei, Pasaniuc, Bogdan, Julienne, Hanna, Aschard, Hugues, Shi, Huwenbo, Yengo, Loic, Polimanti, Renato, Ghoussaini, Maya, Schwartzentruber, Jeremy, Dunham, Ian, Chwialkowska, Karolina, Francescatto, Margherita, Trankiem, Amy, Balaconis, Mary K., Davis, Lea, Lee, Sulggi, Priest, James, Renieri, Alessandra, Sankaran, Vijay G., Van Heel, David, Deelen, Patrick, Richards, J. Brent, Nakanishi, Tomoko, Biesecker, Les, Kerchberger, V. Eric, Baillie, J. Kenneth, Mari, Francesca, Bernasconi, Anna, Baillie, Stefano Ceri, Canakoglu, Arif, Wolford, Brooke, Faucon, Annika, Dutta, Atanu Kumar, Schurmann, Claudia, Harry, Emi, Birney, Ewan, Nguyen, Huy, Nasir, Jamal, Kaunisto, Mari, Solomonson, Matthew, Dueker, Nicole, Vadgama, Nirmal, Limou, Sophie, Rahmouni, Souad, Mbarek, Hamdi, Darwish, Dima, Uddin, Md Mesbah, Albertos, Raquel, P��rez-Tur, Jordi, Li, Ruolin, Folkersen, Lasse, Moltke, Ida, Koelling, Nils, Teumer, Alexander, Kousathanas, Athanasios, Utrilla, Alicia, Verdugo, Ricardo A., Z��rate, Ruth, Medina-G��mez, Carolina, G��mez-Cabrero, David, Carnero-Montoro, Elena, Cadilla, Carmen L., Moreno-Estrada, Andr��s, Garmendia, Adriana, Moya, Leire, Sedaghati-Khayat, Bahar, Boua, Palwend�� Romuald, Fav��, Marie-Julie, Francioli, Laurent, Lema��on, Audrey, Migeotte, Isabelle, Patel, Sanjay, Varnai, Reka, Szentpeteri, Jozsef L., Sipeky, Csilla, Colombo, Francesca, Von Hohenstaufen, Kathrin, Lio, Pietro, Vallerga, Costanza, Wang, Qingbo, Tanigawa, Yosuke, Im, Hogune, Han, Chulho, Song, Han, Lim, Jiwoo, Lee, Younhe, Kim, Sugyeong, Im, Sangyoon, Atanasovska, Biljana, Ahmad, Hajar Fauzan, Boer, Cindy, Jansen, Philip, Franke, Lude, Kaja, El��bieta, Pasko, Dorota, Kennis-Szilagyi, Ingrid, Kornilov, Sergey A., Prijatelj, Vid, Proki��, Ivana, Sivanadhan, Ilangkumaran, Perumal, Sarala, Esmaeeli, Sahar, Pearson, Nathaniel M., Auton, Adam, Shelton, Janie F., Shastri, Anjali J., Filshtein-Sonmez, Teresa, Coker, Daniella, Symons, Antony, Esparza-Gordillo, Jorge, Aslibekyan, Stella, O���Connell, Jared, Ye, Chelsea, Weldon, Catherine H., Perera, Minoli, O���Leary, Kevin, Tuck, Matthew, O���Brien, Travis, Meltzer, David, O���Donnell, Peter, Nutescu, Edith, Yang, Guang, Alarcon, Cristina, Herrmann, Stefanie, Mazurek, Sophia, Banagan, Jeff, Hamidi, Zacharia, Barbour, April, Raffat, Noora, Moreno, Diana, Friedman, Paula, Ferwerda, Bart, Van De Beek, Diederik, Brouwer, Matthijs C., Vlaar, Alexander P. J., Wiersinga, W. Joost, Posthuma, Danielle, Tissink, Elleke, Koos Zwinderman, A. H., Uffelmann, Emil, Van Agtmael, Michiel, Algera, Anne Geke, Van Baarle, Frank, Bax, Diane, Beudel, Martijn, Jan Bogaard, Harm, Bomers, Marije, Bonta, Peter I., Bos, Lieuwe, Botta, Michela, De Brabander, Justin, De Bree, Godelieve, De Bruin, Sanne, Bugiani, Marianna, Bulle, Esther, Chouchane, Osoul, Cloherty, Alex, Dongelmans, Dave, Elbers, Paul, Fleuren, Lucas, Geerlings, Suzanne, Geerts, Bart, Geijtenbeek, Theo, Girbes, Armand, Goorhuis, Bram, Grobusch, Martin P., Hafkamp, Florianne, Hagens, Laura, Hamann, Jorg, Harris, Vanessa, Hemke, Robert, Hermans, Sabine M., Heunks, Leo, Hollmann, Markus, Horn, Janneke, Hovius, Joppe W., De Jong, Menno D., Koning, Rutger, Van Mourik, Niels, Nellen, Jeannine, Nossent, Esther J., Paulus, Frederique, Peters, Edgar, Van Der Poll, Tom, Preckel, Bennedikt, Prins, Jan M., Raasveld, Jorinde, Reijnders, Tom, Schinkel, Michiel, Schultz, Marcus J., Schuurman, Alex, Sigaloff, Kim, Smit, Marry, Stijnis, Cornelis S., Stilma, Willemke, Teunissen, Charlotte, Thoral, Patrick, Tsonas, Anissa, Van Der Valk, Marc, Veelo, Denise, De Vries, Heder, Van Vugt, Mich��le, Wouters, Dorien, Minnaar, Ren�� P., Kromhout, Adrie, Van Uffelen, Kees W. J., Wolterman, Ruud A., Roberts, Genevieve, Park, Danny, Ball, Catherine A., Coignet, Marie, McCurdy, Shannon, Knight, Spencer, Partha, Raghavendran, Rhead, Brooke, Zhang, Miao, Berkowitz, Nathan, Gaddis, Michael, Noto, Keith, Ruiz, Luong, Pavlovic, Milos, Hong, Eurie L., Rand, Kristin, Girshick, Ahna, Guturu, Harendra, Baltzell, Asher Haug, Guntz, Julien, Beguin, Yves, Pigazzini, Sara, Nkambule, Lindokuhle, Bouysran, Youssef, Busson, Adeline, Peyrassol, Xavier, Wilkin, Fran��oise, Pichon, Bruno, Smits, Guillaume, Vandernoot, Isabelle, Goffard, Jean-Christophe, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gilles, Guiot, Julien, Jadot, Laurent, Azarzar, Samira, Dellot, Patricia, Gofflot, St��phanie, Claassen, Sabine, Bertrand, Axelle, Parzibut, Gilles, Clarinval, Mathilde, Moermans, Catherine, Malaise, Olivier, El Kandoussi, Kamilia, Thonon, Rapha��l, Huynen, Pascale, Mesdagh, Alyssia, Melo, Sofia, Jacques, Nicolas, Di Valentin, Emmanuel, Giroule, Fran��ois, Collignon, Alice, Radermecker, Coraline, Lebrun, Marielle, Per��e, H��l��ne, Latour, Samuel, Barada, Olivia, Sanchez, Judit, Josse, Claire, Boujemla, Bouchra, Meunier, Margot, Mariavelle, Emeline, Anania, Sandy, Gazon, H��l��ne, Juszczak, Danusia, Fadeur, Marjorie, Camby, S��verine, Meuris, Christelle, Thys, Marie, Jacques, Jessica, Henket, Monique, L��onard, Philippe, Frippiat, Frederic, Giot, Jean-Baptiste, Sauvage, Anne-Sophie, Von Frenckell, Christian, Mni, Myriam, W��ry, Marie, Staderoli, Alicia, Belhaj, Yasmine, Lambermont, Bernard, Morrison, David R., Mooser, Vincent, Forgetta, Vincenzo, Li, Rui, Ghosh, Biswarup, Laurent, Laetitia, Belisle, Alexandre, Henry, Danielle, Abdullah, Tala, Adeleye, Olumide, Mamlouk, Noor, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Vulesevic, Branka, Bouab, Meriem, Guzman, Charlotte, Petitjean, Louis, Tselios, Chris, Xue, Xiaoqing, Afilalo, Jonathan, Afilalo, Marc, Oliveira, Maureen, Brenner, Bluma, Brassard, Nathalie, Durand, Madeleine, Schurr, Erwin, Lepage, Pierre, Ragoussis, Jiannis, Auld, Daniel, Chass��, Micha��l, Kaufmann, Daniel E., Lathrop, G. Mark, Adra, Darin, Davis, Lea K., Cox, Nancy J., Below, Jennifer E., Sealock, Julia M., Faucon, Annika B., Shuey, Megan M., Polikowsky, Hannah G., Petty, Lauren E., Shaw, Douglas M., Chen, Hung-Hsin, Zhu, Wanying, Ludwig, Kerstin U., Schr��der, Julia, Maj, Carlo, Rolker, Selina, N��then, Markus M., Fazaal, Julia, Keitel, Verena, Jensen, Bj��rn-Erik Ole, Feldt, Torsten, Kurth, Ingo, Marx, Nikolaus, Dreher, Michael, Pink, Isabell, Cornberg, Markus, Illig, Thomas, Lehmann, Clara, Schommers, Philipp, Augustin, Max, Rybniker, Jan, Knopp, Lisa, Eggermann, Thomas, Volland, Sonja, Altm��ller, Janine, Berger, Marc M., Brenner, Thorsten, Hinney, Anke, Witzke, Oliver, Bals, Robert, Herr, Christian, Ludwig, Nicole, Walter, J��rn, Fuchsberger, Christian, Pattaro, Cristian, De Grandi, Alessandro, Pramstaller, Peter, Emmert, David, Melotti, Roberto, Foco, Luisa, Mascalzoni, Deborah, G��gele, Martin, Domingues, Francisco, Hicks, Andrew, Gignoux, Christopher R., Wicks, Stephen J., Crooks, Kristy, Barnes, Kathleen C., Daya, Michelle, Shortt, Jonathan, Rafaels, Nicholas, Chavan, Sameer, Goldstein, David B., Kiryluk, Krzysztof, Sengupta, Soumitra, Chung, Wendy, Reilly, Muredach P., Khan, Atlas, Wang, Chen, Povysil, Gundula, Bhardwaj, Nitin, Gharavi, Ali G., Ionita-Laza, Iuliana, Shang, Ning, O���Byrne, Sheila M., Nandakumar, Renu, Menon, Amritha, So, Yat S., Hod, Eldad, Pendrick, Danielle, Park, Soo-Kyung, Kim, Hyung-Lae, Kang, Chang Kyung, Lee, Hyo-Jung, Song, Kyoung-Ho, Jae Yoon, Kyung, Paik, Nam-Jong, Seok, Woojin, Yoon, Heejun, Joo, Eun-Jeong, Chang, Yoosoo, Ryu, Seungho, Park, Wan Beom, Su Park, Jeong, Un Park, Kyoung, Ham, Sin Young, Jung, Jongtak, Kim, Eu Suk, Kim, Hong Bin, Ellinghaus, David, Degenhardt, Frauke, C��ceres, Mario, Juzenas, Simonas, Lenz, Tobias L., Albillos, Agust��n, Juli��, Antonio, Heidecker, Bettina, Garcia, Federico, Kurth, Florian, Tran, Florian, Hanses, Frank, Zoller, Heinz, Holter, Jan C., Fern��ndez, Javier, Sander, Leif Erik, Rosenstiel, Philip, Koehler, Philipp, De Cid, Rafael, Asselta, Rosanna, Schreiber, Stefan, Hehr, Ute, Prati, Daniele, Baselli, Guido, Valenti, Luca, Bujanda, Luis, Banales, Jesus M., Duga, Stefano, D���Amato, Mauro, Romero-G��mez, Manuel, Buti, Maria, Invernizzi, Pietro, Franke, Andre, Hov, Johannes R., Karlsen, Tom H., Folseraas, Trine, Maya-Miles, Douglas, Teles, Ana, Azuure, Clinton, Wacker, Eike Matthias, Uellendahl-Werth, Florian, ElAbd, Hesham, Arora, Jatin, Lerga-Jaso, Jon, Wienbrandt, Lars, R��hlemann, Malte Christoph, Wendorff, Mareike, Vadla, May Sissel, Lenning, Ole Bernt, ��zer, Onur, Myhre, Ronny, Raychaudhuri, Soumya, Tanck, Anja, Gassner, Christoph, Hemmrich-Stanisak, Georg, K��ssens, Jan, Figuera Basso, Maria E., Schulzky, Martin, Wittig, Michael, Braun, Nicole, Wesse, Tanja, Albrecht, Wolfgang, Yi, Xiaoli, Ortiz, Aaron Blandino, Chercoles, Adolfo Garrido, Ruiz, Agust��n, Mantovani, Alberto, Holten, Aleksander Rygh, Mayer, Alena, Cherubini, Alessandro, Protti, Alessandro, Aghemo, Alessio, Gerussi, Alessio, Ramirez, Alfredo, Braun, Alice, Barreira, Ana, Lleo, Ana, Kildal, Anders Benjamin, Gl��ck, Andreas, Nolla, Anna Carreras, Latiano, Anna, Dyrhol-Riise, Anne Ma, Muscatello, Antonio, Voza, Antonio, Rando-Segura, Ariadna, Solier, Aurora, Karina, Banasik, Cortes, Beatriz, Mateos, Beatriz, Nafria-Jimenez, Beatriz, Schaefer, Benedikt, Bellinghausen, Carla, Ferrando, Carlos, Quereda, Carmen, Skurk, Carsten, Thibeault, Charlotte, Spinner, Christoph D., Lange, Christoph, Hu, Cinzia, Cappadona, Claudio, Bianco, Cristiana, Sancho, Cristina, Lihaug Hoff, Dag Arne, Galimberti, Daniela, Jim��nez, David, Pesta��a, David, Toapanta, David, Azzolini, Elena, Scarpini, Elio, Helbig, Elisa T., Urrechaga, Eloisa, Paraboschi, Elvezia Maria, Pontali, Emanuele, Reverter, Enric, Navas, Enrique, Arana, Eunate, S��nchez, F��lix Garc��a, Ceriotti, Ferruccio, Malvestiti, Francesco, Mesonero, Francisco, Pezzoli, Gianni, Lamorte, Giuseppe, Neb, Holger, My, Ilaria, Hern��ndez, Isabel, De Rojas, Itziar, Galv��n-Femenia, Iv��n, Heyckendorf, Jan, Badia, Joan Ramon, Schneider, Jochen, Goikoetxea, Josune, Kraft, Julia, M��ller, Karl Erik, Gaede, Karoline I., Garcia-Etxebarria, Koldo, Tonby, Kristian, Heggelund, Lars, Izquierdo-Sanchez, Laura, Sumoy, Lauro, Lippert, Lena J., Terranova, Leonardo, Garbarino, Lucia, T��llez, Luis, Roade, Luisa, Ostadreza, Mahnoosh, Intxausti, Maider, Kogevinas, Manolis, Guti��rrez-Stampa, Mar��a A., Vehreschild, Maria J. G. T., Marqui��, Marta, Castoldi, Massimo, Cecconi, Maurizio, Boada, Merc��, Seilmaier, Michael J., Mazzocco, Michela, Rodr��guez-Gand��a, Miguel, Ayo, Natale Imaz, Blay, Natalia, Mart��nez, Nilda, Cornely, Oliver A., Palmieri, Orazio, Tentorio, Paolo, Rodrigues, Pedro M., Espa��a, Pedro P., Hoffmann, Per, Bacher, Petra, Suwalski, Phillip, De Pablo, Ra��l, Nieto, Rosa, Badalamenti, Salvatore, Ciesek, Sandra, Bombace, Sara, Wilfling, Sibylle, Brunak, S��ren, Heilmann-Heimbach, Stefanie, Ripke, Stephan, Bahmer, Thomas, Landmesser, Ulf, Protzer, Ulrike, Rimoldi, Valeria, Skogen, Vegard, Andrade, Victor, Moreno, Victor, Poller, Wolfgang, Farre, Xavier, Wang, Xiaomin, Khodamoradi, Yascha, Karadeniz, Zehra, De Salazar, Adolfo, Palom, Adriana, Garcia-Fernandez, Alba-Estela, Blanco-Grau, Albert, Zanella, Alberto, Bandera, Alessandra, Nebel, Almut, Biondi, Andrea, Caballero-Garralda, Andrea, Gori, Andrea, Lind, Andreas, Fracanzani, Anna Ludovica, Peschuck, Anna, Pesenti, Antonio, De La Horra, Carmen, Milani, Chiara, Paccapelo, Cinzia, Angelini, Claudio, Cea, Cristina, Mu��iz-Diaz, Eduardo, Sandoval, Elena, Calder��n, Enrique J., Sollig��rd, Erik, Aziz, F��tima, Martinelli-Boneschi, Filippo, Peyvandi, Flora, Blasi, Francesco, Medrano, Francisco J., Rodriguez-Frias, Francisco, M��ller, Fredrik, Grasselli, Giacomo, Costantino, Giorgio, Cardamone, Giulia, Foti, Giuseppe, Matullo, Giuseppe, Kurihara, Hayato, Afset, Jan Egil, Dam��s, Jan Kristian, Ampuero, Javier, Mart��n, Javier, Erdmann, Jeanette, Bergan, Jonas, Goerg, Siegfried, Ferrusqu��a-Acosta, Jose, Quero, Jose Hern��ndez, Delgado, Juan, Guerrero, Juan M., Risnes, Kari, Bettini, Laura Rachele, Moreira, Leticia, Gustad, Lise Tuset, Santoro, Luigi, Scudeller, Luigia, Riveiro-Barciela, Mar, Schaefer, Marco, Carrabba, Maria, Valsecchi, Maria G., Hernandez-Tejero, Mar��a, Acosta-Herrera, Marialbert, D���Angi��, Mariella, Baldini, Marina, Cazzaniga, Marina, Ciccarelli, Michele, Bocciolone, Monica, Miozzo, Monica, Chueca, Natalia, Montano, Nicola, Faverio, Paola, Preatoni, Paoletta, Bonfanti, Paolo, Omodei, Paolo, Castro, Pedro, Ferrer, Ricard, Gualtierotti, Roberta, Gallego-Dur��n, Roc��o, Morilla, Rub��n, Haider, Sammra, Marsal, Sara, Aneli, Serena, Pelusi, Serena, Bosari, Silvano, Aliberti, Stefano, Dudman, Susanne, Zheng, Tenghao, Pumarola, Tomas, Cejudo, Trinidad Gonzalez, Monzani, Valter, Friaza, Vicente, Peter, Wolfgang, Dopazo, Ximo, May, Sandra, Grimsrud, Marit M., Gudbjartsson, Daniel F., Stefansson, Kari, Sulem, Patrick, Sveinbjornsson, Gardar, Melsted, Pall, Norddahl, Gudmundur, Swerford Moore, Kristjan Helgi, Thorsteinsdottir, Unnur, Holm, Hilma, Alarc��n-Riquelme, Marta E., Bernardo, David, Mart��nez-Bueno, Manuel, Rello, Silvia Rojo, Magi, Reedik, Milani, Lili, Metspalu, Andres, Laisk, Triin, L��ll, Kristi, Lepamets, Maarja, Esko, T��nu, Reimann, Ene, Naaber, Paul, Laane, Edward, Pesukova, Jaana, Peterson, P��rt, Kisand, Kai, Tabri, Jekaterina, Allos, Raili, Hensen, Kati, Starkopf, Joel, Ringmets, Inge, Tamm, Anu, Kallaste, Anne, Alavere, Helene, Metsalu, Kristjan, Puusepp, Mairo, Kristiansson, Kati, Koskelainen, Sami, Perola, Markus, Donner, Kati, Kivinen, Katja, Palotie, Aarno, Rivolta, Carlo, Bochud, Pierre-Yves, Bibert, St��phanie, Boillat, No��mie, Nussle, Semira Gonseth, Albrich, Werner, Quinodoz, Mathieu, Kamdar, Dhryata, Suh, No��mie, Neofytos, Dionysios, Erard, V��ronique, Voide, Cathy, Bochud, P. Y., Rivolta, C., Bibert, S., Quinodoz, M., Kamdar, D., Neofytos, D., Erard, V., Voide, C., Friolet, R., Vollenweider, P., Pagani, J. L., Oddo, M., Zu Bentrup, F. Meyer, Conen, A., Clerc, O., Marchetti, O., Guillet, A., Guyat-Jacques, C., Foucras, S., Rime, M., Chassot, J., Jaquet, M., Viollet, R. Merlet, Lannepoudenx, Y., Portopena, L., Desgranges, F., Filippidis, P., Gu��ry, B., Haefliger, D., Kampouri, E. E., Manuel, O., Munting, A., Papadimitriou-Olivgeris, M., Regina, J., Rochat-Stettler, L., Suttels, V., Tadini, E., Tschopp, J., Van Singer, M., Viala, B., Boillat-Blanco, N., Brahier, T., H��gli, O., Meuwly, J. Y., Pantet, O., Nussle, S. Gonseth, Bochud, M., D���Acremont, V., Younes, S. Estoppey, Albrich, W. C., Suh, N., Cerny, A., O���Mahony, L., Von Mering, C., Frischknecht, M., Kleger, G.-R., Filipovic, M., Kahlert, C. R., Wozniak, H., Negro, T. Rochat, Pugin, J., Bouras, K., Knapp, C., Egger, T., Perret, A., Montillier, P., Di Bartolomeo, C., Barda, B., Carreras, Anna, Galv��n-Femen��a, Iv��n, Farr��, Xavier, Cort��s, Beatriz, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Garcia-Aymerich, Judith, Casta��o-Vinyals, Gemma, Doba��o, Carlota, Gori, Marco, Mondelli, Mario Umberto, Castelli, Francesco, Vaghi, Massimo, Rusconi, Stefano, Montagnani, Francesca, Bargagli, Elena, Franchi, Federico, Mazzei, Maria Antonietta, Cantarini, Luca, Tacconi, Danilo, Feri, Marco, Scala, Raffaele, Spargi, Genni, Nencioni, Cesira, Bandini, Maria, Caldarelli, Gian Piero, Spagnesi, Maurizio, Canaccini, Anna, Ognibene, Agostino, D���Arminio Monforte, Antonella, Girardis, Massimo, Antinori, Andrea, Francisci, Daniela, Schiaroli, Elisabetta, Scotton, Pier Giorgio, Panese, Sandro, Scaggiante, Renzo, Monica, Matteo Della, Capasso, Mario, Fiorentino, Giuseppe, Castori, Marco, Aucella, Filippo, Di Biagio, Antonio, Masucci, Luca, Valente, Serafina, Mandal��, Marco, Zucchi, Patrizia, Giannattasio, Ferdinando, Coviello, Domenico A., Mussini, Cristina, Bosio, Giancarlo, Tavecchia, Luisa, Crotti, Lia, Rizzi, Marco, La Rovere, Maria Teresa, Sarzi-Braga, Simona, Bussotti, Maurizio, Ravaglia, Sabrina, Artuso, Rosangela, Perrella, Antonio, Romani, Davide, Bergomi, Paola, Catena, Emanuele, Vincenti, Antonella, Ferri, Claudio, Grassi, Davide, Pessina, Gloria, Tumbarello, Mario, Di Pietro, Massimo, Sabrina, Ravaglia, Luchi, Sauro, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Paciosi, Francesco, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, De Vivo, Oreste, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, Perticaroli, Valentina, Furini, Simone, Dei, Simona, Benetti, Elisa, Picchiotti, Nicola, Sanarico, Maurizio, Ceri, Stefano, Pinoli, Pietro, Raimondi, Francesco, Biscarini, Filippo, Stella, Alessandra, Bergomi, Mattia, Zguro, Kristina, Capitani, Katia, Tanfoni, Marco, Fallerini, Chiara, Daga, Sergio, Baldassarri, Margherita, Fava, Francesca, Frullanti, Elisa, Valentino, Floriana, Doddato, Gabriella, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Croci, Susanna, Meloni, Ilaria, Mencarelli, Maria Antonietta, Lo Rizzo, Caterina, Pinto, Anna Maria, Beligni, Giada, Tommasi, Andrea, Di Sarno, Laura, Palmieri, Maria, Carriero, Miriam Lucia, Alaverdian, Diana, Iuso, Nicola, Inchingolo, Gabriele, Busani, Stefano, Bruno, Raffaele, Vecchia, Marco, Belli, Mary Ann, Mantovani, Stefania, Ludovisi, Serena, Quiros-Roldan, Eugenia, Antoni, Melania Degli, Zanella, Isabella, Siano, Matteo, Emiliozzi, Arianna, Fabbiani, Massimiliano, Rossetti, Barbara, Zanelli, Giacomo, Bergantini, Laura, D���Alessandro, Miriana, Cameli, Paolo, Bennet, David, Anedda, Federico, Marcantonio, Simona, Scolletta, Sabino, Guerrini, Susanna, Conticini, Edoardo, Frediani, Bruno, Spertilli, Chiara, Donati, Alice, Guidelli, Luca, Corridi, Marta, Croci, Leonardo, Piacentini, Paolo, Desanctis, Elena, Cappelli, Silvia, Verzuri, Agnese, Anemoli, Valentina, Pancrazi, Alessandro, Lorubbio, Maria, Merlini, Esther, Miraglia, Federica Gaia, Venturelli, Sophie, Cossarizza, Andrea, Vergori, Alessandra, Gabrieli, Arianna, Riva, Agostino, Andretta, Francesca, Gatti, Francesca, Parisi, Saverio Giuseppe, Baratti, Stefano, Piscopo, Carmelo, Russo, Roberta, Andolfo, Immacolata, Iolascon, Achille, Carella, Massimo, Merla, Giuseppe, Squeo, Gabriella Maria, Raggi, Pamela, Marciano, Carmen, Perna, Rita, Bassetti, Matteo, Sanguinetti, Maurizio, Giorli, Alessia, Salerni, Lorenzo, Parravicini, Pierpaolo, Menatti, Elisabetta, Trotta, Tullio, Coiro, Gabriella, Lena, Fabio, Martinelli, Enrico, Mancarella, Sandro, Gabbi, Chiara, Maggiolo, Franco, Ripamonti, Diego, Bachetti, Tiziana, Suardi, Claudia, Parati, Gianfranco, Bott��, Giordano, Di Domenico, Paolo, Rancan, Ilaria, Bianchi, Francesco, Colombo, Riccardo, Van Heel, David A., Hunt, Karen A., Trembath, Richard C., Huang, Qin Qin, Martin, Hilary C., Mason, Dan, Trivedi, Bhavi, Wright, John, Finer, Sarah, Griffiths, Christopher J., Akhtar, Shaheen, Anwar, Mohammad, Arciero, Elena, Ashraf, Samina, Breen, Gerome, Chung, Raymond, Curtis, Charles J., Chowdhury, Maharun, Colligan, Grainne, Deloukas, Panos, Durham, Ceri, Griffiths, Chris, Hurles, Matt, Hussain, Shapna, Islam, Kamrul, Khan, Ahsan, Khan, Amara, Lavery, Cath, Lee, Sang Hyuck, Lerner, Robin, MacArthur, Daniel, MacLaughlin, Bev, Martin, Hilary, Miah, Shefa, Newman, Bill, Safa, Nishat, Tahmasebi, Farah, Smith, Albert V., Boughton, Andrew P., Li, Kevin W., LeFaive, Jonathon, Annis, Aubrey, Jannes, Cinthia E., Krieger, Jose E., Pereira, Alexandre C., Velho, Mariliza, Marques, Emanuelle, Lima, Isabella Ramos, Tada, Mauricio Teruo, Valino, Karina, McCarthy, Mark, Rosenberger, Carrie, Lee, Jong Eun, Chang, Diana, Hammer, Christian, Hunkapiller, Julie, Mahajan, Anubha, Pendergrass, Sarah, Sucheston-Campbell, Lara, Yaspan, Brian, Lee, Hyun Soo, Shin, Eunsoon, Jang, Hye Yoon, Kim, Sunmie, Kym, Sungmin, Kim, Yeon-Sook, Jeong, Hyeongseok, Kwon, Ki Tae, Kim, Shin-Woo, Kim, Jin Yong, Jang, Young Rock, Kim, Hyun Ah, Lee, Ji Yeon, Lee, Jeong Eun, Lee, Shinwon, Choe, Kang-Won, Kang, Yu Min, Jee, Sun Ha, Jung, Keum Ji, Parikh, Victoria, Ashley, Euan, Wheeler, Matthew, Rivas, Manuel, Bustamante, Carlos, Pinksy, Benjamin, Febbo, Phillip, Farh, Kyle, Schroth, Gary P., DeSouza, Francis, Dalton, Karen, Christle, Jeff, Deboever, Christopher, Szalma, S��ndor, Rubinacci, Simone, Delaneau, Olivier, Gorzynski, John, De Jong, Hannah, Sutton, Shirley, Youlton, Nathan, Joshi, Ruchi, Jimenez-Morales, David, Hughes, Christopher, Amar, David, Ioannidis, Alex, Hershman, Steve, Kirillova, Anna, Seo, Kinya, Huang, Yong, Shoura, Massa, Hammond, Nathan, Watson, Nathaniel, Raja, Archana, Huang, ChunHong, Sahoo, Malaya, Wang, Hannah, Zhen, Jimmy, Rakitko, Alexander, Ilinsky, Valery, Yermakovich, Danat, Popov, Iaroslav, Chernitsov, Alexander, Kovalenko, Elena, Krasnenko, Anna, Plotnikov, Nikolay, Stetsenko, Ivan, Kim, Anna, Cirulli, Elizabeth T., Schiabor Barrett, Kelly M., Bolze, Alexandre, White, Simon, Washington, Nicole L., Lu, James T., Riffle, Stephen, Tanudjaja, Francisco, Wang, Xueqing, Ramirez, Jimmy M., Leonetti, Nicole, Sandoval, Efren, Neveux, Iva, Dabe, Shaun, Grzymski, Joseph J., Esteban Mi��ano, Juan Ignacio, Aguirre, Luis A., L��pez-Collazo, Eduardo, De La Mata Pazos, Manuel, Cerrato, Luciano, Lozano-Rodr��guez, Roberto, Avenda��o-Ortiz, Jos��, Arcos, Ver��nica Terr��n, Montalb��n-Hern��ndez, Karla Marina, Quiroga, Jaime Valent��n, Pascual-Iglesias, Alejandro, Maroun-Eid, Charbel, Mart��n-Quir��s, Alejandro, Namkoong, Ho, Imoto, Seiya, Katayama, Kazuhiko, Fukunaga, Koichi, Kitagawa, Yuko, Sato, Toshiro, Hasegawa, Naoki, Kumanogoh, Atsushi, Kimura, Akinori, Ai, Masumi, Tokunaga, Katsushi, Kanai, Takanori, Miyano, Satoru, Ogawa, Seishi, Edahiro, Ryuya, Sonehara, Kyuto, Shirai, Yuya, Ishii, Makoto, Kabata, Hiroki, Masaki, Katsunori, Kamata, Hirofumi, Ikemura, Shinnosuke, Chubachi, Shotaro, Okamori, Satoshi, Terai, Hideki, Tanaka, Hiromu, Morita, Atsuho, Lee, Ho, Asakura, Takanori, Sasaki, Junichi, Morisaki, Hiroshi, Uwamino, Yoshifumi, Nanki, Kosaku, Mikami, Yohei, Tomono, Kazunori, Kato, Kazuto, Matsuda, Fumihiko, Takahashi, Meiko, Hizawa, Nobuyuki, Takeda, Yoshito, Hirata, Haruhiko, Shiroyama, Takayuki, Miyawaki, Satoru, Suzuki, Ken, Maeda, Yuichi, Nii, Takuro, Noda, Yoshimi, Niitsu, Takayuki, Adachi, Yuichi, Enomoto, Takatoshi, Amiya, Saori, Hara, Reina, Takahashi, Kunihiko, Anzai, Tatsuhiko, Hasegawa, Takanori, Ito, Satoshi, Koike, Ryuji, Endo, Akifumi, Uchimura, Yuji, Miyazaki, Yasunari, Honda, Takayuki, Tateishi, Tomoya, Tohda, Shuji, Ichimura, Naoya, Sonobe, Kazunari, Sassa, Chihiro, Nakajima, Jun, Nannya, Yasuhito, Omae, Yosuke, Takahashi, Kazuhisa, Harada, Norihiro, Hiki, Makoto, Takagi, Haruhi, Nakamura, Ai, Tagaya, Etsuko, Kawana, Masatoshi, Arimura, Ken, Ishiguro, Takashi, Takayanagi, Noboru, Isono, Taisuke, Takaku, Yotaro, Takano, Kenji, Anan, Ryusuke, Nakajima, Yukiko, Nakano, Yasushi, Nishio, Kazumi, Ueda, Soichiro, Hayashi, Reina, Tateno, Hiroki, Hase, Isano, Yoshida, Shuichi, Suzuki, Shoji, Mitamura, Keiko, Saito, Fumitake, Ueda, Tetsuya, Azuma, Masanori, Nagasaki, Tadao, Yasui, Yoshinori, Hasegawa, Yoshinori, Mutoh, Yoshikazu, Yoshiyama, Takashi, Shoko, Tomohisa, Kojima, Mitsuaki, Adachi, Tomohiro, Ishikawa, Motonao, Takahashi, Kenichiro, Watanabe, Kazuyoshi, Manabe, Tadashi, Ito, Fumimaro, Fukui, Takahiro, Funatsu, Yohei, Koh, Hidefumi, Hirai, Yoshihiro, Kawashima, Hidetoshi, Narita, Atsuya, Niwa, Kazuki, Sekikawa, Yoshiyuki, Saito, Fukuki, Yoshiya, Kazuhisa, Yoshihara, Tomoyuki, Suzuki, Yusuke, Nakayama, Sohei, Masuzawa, Keita, Nishi, Koichi, Nishitsuji, Masaru, Tani, Maiko, Inoue, Takashi, Hirano, Toshiyuki, Kobayashi, Keigo, Miyazawa, Naoki, Kimura, Yasuhiro, Sado, Reiko, Ogura, Takashi, Kitamura, Hideya, Murohashi, Kota, Nakachi, Ichiro, Baba, Rie, Arai, Daisuke, Fuke, Satoshi, Saito, Hiroshi, Kuwahara, Naota, Fujiwara, Akiko, Okada, Takenori, Baba, Tomoya, Noda, Junya, Mashimo, Shuko, Yagi, Kazuma, Shiomi, Tetsuya, Hashiguchi, Mizuha, Odani, Toshio, Mochimaru, Takao, Oyamada, Yoshitaka, Mori, Nobuaki, Izumi, Namiki, Nagata, Kaoru, Taki, Reiko, Murakami, Koji, Yamada, Mitsuhiro, Sugiura, Hisatoshi, Hayashi, Kentaro, Shimizu, Tetsuo, Gon, Yasuhiro, Fujitani, Shigeki, Tsuchida, Tomoya, Yoshida, Toru, Kagaya, Takashi, Kita, Toshiyuki, Sakagami, Satoru, Kimizuka, Yoshifumi, Kawana, Akihiko, Nakamura, Yoshihiko, Ishikura, Hiroyasu, Takata, Tohru, Kikuchi, Takahide, Taniyama, Daisuke, Nakamura, Morio, Kodama, Nobuhiro, Kaneyama, Yasunari, Maeda, Shunsuke, Nagasaki, Yoji, Okamoto, Masaki, Ishihara, Sayoko, Ito, Akihiro, Chihara, Yusuke, Takeuchi, Mayumi, Onoi, Keisuke, Hashimoto, Naozumi, Wakahara, Keiko, Ando, Akira, Masuda, Makoto, Wakabayashi, Aya, Watanabe, Hiroki, Sageshima, Hisako, Nakada, Taka-Aki, Abe, Ryuzo, Shimada, Tadanaga, Kawamura, Kodai, Ichikado, Kazuya, Nishiyama, Kenta, Yamasaki, Masaki, Hashimoto, Satoru, Kusaka, Yu, Ohba, Takehiko, Isogai, Susumu, Takada, Minoru, Kanda, Hidenori, Komase, Yuko, Sano, Fumiaki, Asano, Koichiro, Oguma, Tsuyoshi, Harada, Masahiro, Takahashi, Takeshi, Shibusawa, Takayuki, Abe, Shinji, Kono, Yuta, Togashi, Yuki, Izumo, Takehiro, Inomata, Minoru, Awano, Nobuyasu, Ogawa, Shinichi, Ogata, Tomouki, Ishihara, Shoichiro, Kanehiro, Arihiko, Ozaki, Shinji, Fuchimoto, Yasuko, Kitagawa, Yuichiro, Yoshida, Shozo, Ogura, Shinji, Nishiyama, Kei, Yoshida, Kousuke, Beppu, Satoru, Fukuyama, Satoru, Eriguchi, Yoshihiro, Yonekawa, Akiko, Inoue, Yoshiaki, Yamagata, Kunihiro, Chiba, Shigeru, Narumoto, Osamu, Nagai, Hideaki, Ooshima, Nobuharu, Motegi, Mitsuru, Sagara, Hironori, Tanaka, Akihiko, Ohta, Shin, Shibata, Yoko, Tanino, Yoshinori, Sato, Yuki, Yamada, Yuichiro, Hashino, Takuya, Shinoki, Masato, Iwagoe, Hajime, Imamura, Tomonori, Umeda, Akira, Shimada, Hisato, Endo, Mayu, Hayashi, Shinichi, Takahashi, Mai, Nakano, Shigefumi, Yatomi, Masakiyo, Maeno, Toshitaka, Ishii, Tomoo, Utsugi, Mitsuyoshi, Ono, Akihiro, Kanaoka, Kensuke, Ihara, Shoichi, Komuta, Kiyoshi, Boezen, Marike, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., Van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Obeidat, Ma���en, Hern��ndez Cordero, Ana I., Sin, Don D., Boss��, Yohan, Joubert, Philippe, Hao, Ke, Nickle, David, Timens, Wim, Van Den Berge, Maarten, Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Z��llner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Tess, Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O���Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Aris, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Jan Hottenga, Jouke, Bartels, Meike, De Geus, Eco J. C., Nivard, Michel G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Zara, Federico, Salpietro, Vincenzo, Scala, Marcello, Iacomino, Michele, Scudieri, Paolo, Bocciardi, Renata, Minetti, Carlo, Riva, Antonella, Vari, Maria Stella, Rahier, Jean-Fran��ois, Giorgio, Elisa, Carli, Diana, Louis, Edouad, Bulik, Cynthia M., Land��n, Mikael, Brusco, Alfredo, Ferrero, Giovanni Battista, Madia, Francesca, Fund��n, Bengt, Ismail, Said I., Saad, Chadi, Al-Sarraj, Yaser, Badji, Radja Messai, Al-Muftah, Wadha, Al Thani, Asma, Afifi, Nahla, Klovins, Janis, Rovite, Vita, Rescenko, Raimonds, Peculis, Raitis, Ustinova, Monta, Zeberg, Hugo, Frithiof, Robert, Hultstr��m, Michael, Lipcsey, Miklos, Johnson, Ruth, Geschwind, Daniel H., Freimer, Nelson, Butte, Manish J., Ding, Yi, Chiu, Alec, Chang, Timothy S., Boutros, Paul, Moutsianas, Loukas, Caulfield, Mark J., Scott, Richard H., Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Wilson, Daniel J., Spencer, Chris A., Crook, Derrick W., Wyllie, David H., O���Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikolas, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Neale, Benjamin M., Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicolas, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Di Angelantonio, Emanuele, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O���Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Mian, Michael, Scaggiante, Federica, Chang, Xiao, Glessner, Joseph R., Hakonarson, Hakon, McGuigan, Peter J., Prockter Moore, Luke Stephen, Vizcaychipi, Marcela Paola, Hall, Kathryn, Campbell, Andy, Nichol, Ailstair, Ward, Geraldine, Page, Valerie Joan, Semple, Malcolm G., Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Christopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B., Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary H., Minton, Jane, Ward, Karl, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, O���Shea, Matthew K., Otahal, Igor, Ostermann, Marlies, Pais, Mark, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Pooni, Jagtur Singh, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ryan, Brendan, Saluja, Taranprit, Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Ustianowski, Andrew, Vallotton, Nick, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Cole, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wooton, Daniel G., Workman, Andrew, Yates, Bryan, Young, Peter, Beale, Rupert, Bretherick, Andrew D., Clohisey, Sara, Fourman, Max Head, Furniss, James, Gountouna, Elvina, Grimes, Graeme, Haley, Chris, Harrison, David, Hayward, Caroline, Keating, Sean, Klaric, Lucija, Klenerman, Paul, Law, Andy, Meynert, Alison M., Millar, Jonathan, Pairo-Castineira, Erola, Parkinson, Nicholas, Ponting, Chris P., Porteous, David J., Rawlik, Konrad, Richmond, Anne, Rowan, Kathy, Russell, Clark D., Shen, Xia, Shih, Barbara, Tenesa, Albert, Vitart, Veronique, Wang, Bo, Wilson, James F., Wu, Yang, Yang, Jian, Yang, Zhijian, Zechner, Marie, Zhai, Ranran, Zheng, Chenqing, Norman, Lisa, Pius, Riinu, Drake, Thomas M., Fairfield, Cameron J., Knight, Stephen R., Mclean, Kenneth A., Murphy, Derek, Shaw, Catherine A., Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Leeming, Gary, Law, Andrew, Wham, Murray, Hendry, Ross, Scott-Brown, James, Begg, Colin, Hinds, Charles, Wai Ho, Antonia Ying, Horby, Peter W., Knight, Julian, Ling, Lowell, Maslove, David, McAuley, Danny, Montgomery, Hugh, Nichol, Alistair, Openshaw, Peter J. M., Summers, Charlotte, Walsh, Timothy, Armstrong, Lisa, Bates, Hayley, Dooks, Emma, Farquhar, Fiona, Hairsine, Brigid, McParland, C., Packham, Sophie, Alldis, Zoe, Astin-Chamberlain, Raine, Bibi, Fatima, Biddle, Jack, Blow, Sarah, Bolton, Matthew, Borra, Catherine, Bowles, Ruth, Burton, Maudrian, Choudhury, Yasmin, Collier, David, Cox, Amber, Easthope, Amy, Ebano, Patrizia, Fotiadis, Stavros, Gurasashvili, Jana, Halls, Rosslyn, Hartridge, Pippa, Kallon, Delordson, Kassam, Jamila, Lancoma-Malcolm, Ivone, Matharu, Maninderpal, May, Peter, Mitchelmore, Oliver, Newman, Tabitha, Patel, Mital, Pheby, Jane, Pinzuti, Irene, Prime, Zoe, Prysyazhna, Oleksandra, Shiel, Julian, Taylor, Melanie, Tierney, Carey, Wood, Suzanne, Zak, Anne, Zongo, Olivier, Forsey, Miranda, Nicholson, Anne, Riches, Joanne, Vertue, Mark, Wasson, Christopher, Finn, Stephanie, Green, Jackie, Collins, Erin, King, Bernadette, Grauslyte, Lina, Hussain, Musarat, Pogreban, Tatiana, Rosaroso, Lace, Salciute, Erika, Franke, George, Wong, Joanna, George, Aparna, Akeroyd, Louise, Bano, Shereen, Bromley, Matt, Gurr, Lucy, Lawton, Tom, Morgan, James, Sellick, Kirsten, Warren, Deborah, Wilkinson, Brian, McGowan, Janet, Ledgard, Camilla, Stacey, Amelia, Pye, Kate, Bellwood, Ruth, Bentley, Michael, Loosley, Ronda, McGuinness, Heather, Tench, Helen, Wolf-Roberts, Rebecca, Gibson, Sian, Lyle, Amanda, McNeela, Fiona, Radhakrishnan, Jayachandran, Hughes, Alistair, Ali, Asifa, Brady, Megan, Dale, Sam, Dance, Annalisa, Gledhill, Lisa, Greig, Jill, Hanson, Kathryn, Holdroyd, Kelly, Home, Marie, Kelly, Diane, Kitson, Ross, Matapure, Lear, Melia, Deborah, Mellor, Samantha, Nortcliffe, Tonicha, Pinnell, Jez, Robinson, Matthew, Shaw, Lisa, Shaw, Ryan, Thomis, Lesley, Wilson, Alison, Wood, Tracy, Bayo, Lee-Ann, Merwaha, Ekta, Ishaq, Tahira, Hanley, Sarah, Antcliffe, David, Banach, Dorota, Brett, Stephen, Coghlan, Phoebe, Fernandez, Ziortza, Gordon, Anthony, Rojo, Roceld, Arias, Sonia Sousa, Templeton, Maie, Jha, Rajeev, Krishnamurthy, Vinodh, Lim, Lai, Bi, Rehana, Scholefield, Barney, Ashton, Lydia, Williams, Alison, Cheyne, Claire, Saunderson, Anne, Allan, Angela, Anderson, Felicity, Kaye, Callum, Liew, Jade, Medhora, Jasmine, Scott, Teresa, Trumper, Erin, Botello, Adriana, Polgarova, Petra, Stroud, Katerina, Meaney, Eoghan, Jones, Megan, Ng, Anthony, Agrawal, Shruti, Pathan, Nazima, White, Deborah, Daubney, Esther, Elston, Kay, Parker, Robert, Reddy, Amie, Turner-Bone, Ian, Wilding, Laura, Harding, Peter, Jacob, Reni, Jones, Cathy, Denmade, Craig, Croft, Maria, White, Ian, Lim, Li, Griffin, Denise, Muchenje, Nycola, Mupudzi, Mcdonald, Partridge, Richard, Conyngham, Jo-Anna, Thomas, Rachel, Wright, Mary, Corral, Maria Alvarez, Bastion, Victoria, Clarke, Daphene, David, Beena, Kent, Harriet, Lorusso, Rachel, Lubimbi, Gamu, Murdoch, Sophie, Penacerrada, Melchizedek, Thomas, Alastair, Valentine, Jennifer, Vochin, Ana, Wulandari, Retno, Djeugam, Brice, Dawson, Joy, Garrioch, Sweyn, Tolson, Melanie, Aldridge, Jonathan, De Almeida Martins, Laura Gomes, Carungcong, Jaime, Beavis, Sarah, Dale, Katie, Gascoyne, Rachel, Hawes, Joanne, Pritchard, Kelly, Stevenson, Lesley, Whileman, Amanda, Cowley, Anne, Highgate, Judith, Crawley, Rikki, Crew, Abigail, Cunningham, Mishell, Daniels, Allison, Harrison, Laura, Hope, Susan, Inweregbu, Ken, Jones, Sian, Lancaster, Nicola, Matthews, Jamie, Nicholson, Alice, Wray, Gemma, Benham, Leonie, Bradshaw, Zena, Brown, Joanna, Caswell, Melanie, Melling, Sarah, Preston, Stephen, Slawson, Nicola, Stoddard, Emma, Warden, Scott, Combes, Edward, Joefield, Teishel, Monnery, Sonja, Beech, Valerie, Trotman, Sallyanne, Hopkins, Bridget, Scriven, James, Thrasyvoulou, Laura, Willis, Heather, Anderson, Susan, Birch, Janine, Collins, Emma, Hammerton, Kate, O���Leary, Ryan, Abernathy, Caroline, Foster, Louise, Gratrix, Andrew, Martinson, Vicky, Parkinson, Priyai, Stones, Elizabeth, Carbral-Ortega, Llucia, Kapoor, Ritoo, Loader, David, Castle, Karen, Brandwood, Craig, Smith, Lara, Clark, Richard, Birchall, Katie, Kolakaluri, Laurel, Baines, Deborah, Sukumaran, Anila, Mapfunde, Isheunesu, Meredith, Megan, Morris, Lucy, Ryan, Lucy, Clark, Amy, Sampson, Julia, Peters, Cecilia, Dent, Martin, Langley, Margaret, Ashraf, Saima, Wei, Shuying, Andrew, Angela, Chablani, Manish, Kirkby, Amy, Netherton, Kimberley, Bates, Michelle, Dasgin, Jo, Gill, Jaspret, Nilsson, Annette, Apetri, Elena, Basikolo, Cathrine, Blackledge, Bethan, Catlow, Laura, Charles, Bethan, Doonan, Reece, Harris, Jade, Harvey, Alice, Horner, Daniel, Knowles, Karen, Lee, Stephanie, Lomas, Diane, Lyons, Chloe, Marsden, Tracy, McLaughlan, Danielle, McMorrow, Liam, Pendlebury, Jessica, Perez, Jane, Poulaka, Maria, Proudfoot, Nicola, Slaughter, Melanie, Slevin, Kathryn, Thomas, Vicky, Walker, Danielle, Michael, Angiy, Collis, Matthew, Clark, Martyn, Coulding, Martina, Jude, Edward, McCormick, Jacqueline, Mercer, Oliver, Potla, Darsh, Rehman, Hafiz, Savill, Heather, Turner, Victoria, Davey, Miriam, Golden, David, Seaman, Rebecca, Hunt, Jodie, Dearden, Joy, Dobson, Emma, Mulcahy, Michelle, Munt, Sheila, O���Connor, Grainne, Philbin, Jennifer, Rishton, Chloe, Tully, Redmond, Winnard, Sarah, Cagova, Lenka, Fofano, Adama, Garner, Lucie, Holcombe, Helen, Mepham, Sue, Mitchell, Alice Michael, Mwaura, Lucy, Praman, K., Vuylsteke, Alain, Zamikula, Julie, Bercades, Georgia, Brealey, David, Hass, Ingrid, MacCallum, Niall, Martir, Gladys, Raith, Eamon, Reyes, Anna, Smyth, Deborah, Taylor, Abigail, Hughes, Rachel Anne, Thomas, Helen, Rees, Alun, Duskova, Michaela, Phipps, Janet, Brooks, Suzanne, Edwards, Michelle, Alexander, Peter, Allen, Schvearn, Bradley-Potts, Joanne, Brantwood, Craig, Egan, Jasmine, Felton, Timothy, Padden, Grace, Ward, Luke, Moss, Stuart, Glasgow, Susannah, Beesley, Kate, Board, Sarah, Kubisz-Pudelko, Agnieszka, Lewis, Alison, Perry, Jess, Pippard, Lucy, Wood, Di, Buckley, Clare, Brown, Alison, Gregory, Jane, O���Connell, Susan, Smith, Tim, Belagodu, Zakaula, Fuller, Bridget, Gherman, Anca, Olufuwa, Olumide, Paramsothy, Remi, Stuart, Carmel, Oakley, Naomi, Kamundi, Charlotte, Tyl, David, Collins, Katy, Silva, Pedro, Taylor, June, King, Laura, Coates, Charlotte, Crowley, Maria, Wakefield, Phillipa, Beadle, Jane, Johnson, Laura, Sargeant, Janet, Anderson, Madeleine, Jardine, Catherine, Williams, Dewi, Parris, Victoria, Quaid, Sheena, Watson, Ekaterina, Melville, Julie, Naisbitt, Jay, Joseph, Rosane, Lazo, Maria, Walton, Olivia, Neal, Alan, Hill, Michaela, Kannan, Thogulava, Wild, Laura, Allan, Elizabeth, Darlington, Kate, Davies, Ffyon, Easton, Jack, Kumar, Sumit, Lean, Richard, Menzies, Daniel, Pugh, Richard, Qiu, Xinyi, Davies, Llinos, Williams, Hannah, Scanlon, Jeremy, Davies, Gwyneth, Mackay, Callum, Lewis, Joannne, Rees, Stephanie, Coetzee, Samantha, Gales, Alistair, Raj, Meena, Sell, Craig, Langton, Helen, Watters, Malcolm, Novis, Catherine, Arbane, Gill, Bociek, Aneta, Campos, Sara, Grau, Neus, Jones, Tim Owen, Lim, Rosario, Marotti, Martina, Whitton, Christopher, Barron, Anthony, Collins, Ciara, Kaul, Sundeep, Passmore, Heather, Prendergast, Claire, Reed, Anna, Rogers, Paula, Shokkar, Rajvinder, Woodruff, Meriel, Middleton, Hayley, Polgar, Oliver, Nolan, Claire, Thwaites, Vicky, Mahay, Kanta, Sri-Chandana, Chunda, Scherewode, Joslan, Stephenson, Lorraine, Marsh, Sarah, Bancroft, Hollie, Bellamy, Mary, Carmody, Margaret, Daglish, Jacqueline, Moore, Faye, Rhodes, Joanne, Sangombe, Mirriam, Kadiri, Salma, Ayers, Amanda, Harrison, Wendy, North, Julie, Cavazza, Anna, Cockrell, Maeve, Corcoran, Eleanor, Depante, Maria, Finney, Clare, Jerome, Ellen, McPhail, Mark, Nayak, Monalisa, Noble, Harriet, O���Reilly, Kevin, Pappa, Evita, Saha, Rohit, Saha, Sian, Smith, John, Knighton, Abigail, Gill, Mandy, Paul, Paul, Ratnam, Valli, Shelton, Sarah, Wynter, Inez, Baptista, David, Crowe, Rebecca, Fernandes, Rita, Herdman-Grant, Rosaleen, Joseph, Anna, Loveridge, Adam, McKenley, India, Morino, Eriko, Naranjo, Andres, Simms, Richard, Sollesta, Kathryn, Swain, Andrew, Venkatesh, Harish, Khera, Jacyntha, Fox, Jonathan, Barber, Russell, Hewitt, Claire, Hilldrith, Annette, Jackson-Lawrence, Karen, Shepardson, Sarah, Wills, Maryanne, Butler, Susan, Tavares, Silvia, Cunningham, Amy, Hindale, Julia, Arif, Sarwat, George, Linsha, Twiss, Sophie, Wright, David, Holland, Maureen, Keenan, Natalie, Lyons, Marc, Wassall, Helen, Marsh, Chris, Mahenthran, Mervin, Carter, Emma, Kong, Thomas, Adanini, Oluronke, Bhatia, Nikhil, Msiska, Maines, Mew, Louise, Mwaura, Esther, Williams, Felicity, Wren, Lynn, Sutherland, Sara-Beth, Battle, Ceri, Brinkworth, Elaine, Harford, Rachel, Murphy, Carl, Newey, Luke, Rees, Tabitha, Williams, Marie, Arnold, Sophie, Hardy, John, Houlden, Henry, Moncur, Eleanor, Tariq, Ambreen, Tucci, Arianna, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Keshet-Price, Jocelyn, Randell, Georgina, Stammers, Katie, Abdelrazik, Marwa, Bakthavatsalam, Dhanalakshmi, Elhassan, Munzir, Ganesan, Arunkumar, Haldeos, Anne, Moreno-Cuesta, Jeronimo, Purohit, Dharam, Vincent, Rachel, Xavier, Kugan, Rohit, Kumar, Alasdair, Frater, Saleem, Malik, David, Carter, Jenkins, Samuel, Lamond, Zoe, Wall, Alanna, Reynolds, Jessica, Campbell, Helen, Thompsom, Maria, Dodds, Steve, Duffy, Stacey, Butcher, Deborah, O���Sullivan, Susie, Butterworth-Cowin, Nicola, Deacon, Bethan, Hibbert, Meg, Pothecary, Carla, Tetla, Dariusz, Woodford, Christopher, Durga, Latha, Kennard-Holden, Gareth, De Gordoa, Laura Ortiz-Ruiz, Peasgood, Emily, Phillips, Claire, Skinner, Denise, Gaylard, Jane, Mullan, Dee, Newman, Julie, Davies, Ellie, Roche, Lisa, Sathe, Sonia, Brimfield, Lutece, Daly, Zoe, Pogson, David, Rose, Steve, Collins, Amy, Khaliq, Waqas, Gude, Estefania Treus, Allen, Louise, Beranova, Eva, Crisp, Nikki, Deery, Joanne, Hazelton, Tracy, Knight, Alicia, Price, Carly, Tilbey, Sorrell, Turki, Salah, Turney, Sharon, Giles, Julian, Booth, Simon, Bell, Gillian, English, Katy, Katary, Amro, Wilcox, Louise, Campbell, Rachael, Clarke, Noreen, Whiteside, Jonathan, Mascarenhas, Mairi, Donaldson, Avril, Matheson, Joanna, Barrett, Fiona, O���Hara, Marianne, O���Keefe, Laura, Bradley, Clare, Collier, Dawn, Walker, Rachel, Maynard, Victoria, Patel, Tahera, Smith, Matthew, Kazi, Aayesha, Hartley, Janice, Dykes, Joseph, Hijazi, Muhammad, Keith, Sarah, Khan, Meherunnisa, Ryan-Smith, Janet, Springle, Philippa, Thomas, Jacqueline, Truman, Nick, Saad, Samuel, Coleman, Dabheoc, Fine, Christopher, Matt, Roseanna, Gay, Bethan, Dalziel, Jack, Ali, Syamlan, Goodchild, Drew, Harling, Rhiannan, Bhatterjee, Ravi, Goddard, Wendy, Davison, Chloe, Duberly, Stephen, Hargreaves, Jeanette, Bolton, Rachel, Verlander, Mark, Williams, Alexandra, Blackman, Helen, Creagh-Brown, Ben, Donlon, Sinead, Michalak-Glinska, Natalia, Mtuwa, Sheila, Pristopan, Veronika, Salberg, Armorel, Smith, Eleanor, Stone, Sarah, Piercy, Charles, Verula, Jerik, Burda, Dorota, Montaser, Rugia, Harden, Lesley, Mayangao, Irving, Marriott, Cheryl, Bradley, Paul, Harris, Celia, Cooper, Joshua, Finch, Cheryl, Liderth, Sarah, Quinn, Alison, Waddington, Natalia, Fidler, Katy, Tagliavini, Emma, Donnelly, Kevin, Abel, Lynn, Brett, Michael, Digby, Brian, Gemmell, Lisa, Hornsby, James, MacGoey, Patrick, O���Neil, Pauline, Price, Richard, Rodden, Natalie, Rooney, Kevin, Sundaram, Radha, Thomson, Nicola, Flanagan, Rebecca, Hughes, Gareth, Latham, Scott, McKenna, Emma, Anderson, Jennifer, Hull, Robert, Rhead, Kat, Branney, Debbie, Frankham, Jordan, Pitts, Sally, White, Nigel, Cristiano, Daniele, Dormand, Natalie, Farzad, Zohreh, Gummadi, Mahitha, Liyanage, Kamal, Patel, Brijesh V., Salmi, Sara, Sloane, Geraldine, Varghese, Mathew, Zborowski, Anelise C., Bean, Sarah, Burt, Karen, Spivey, Michael, Eastgate-Jackson, Christine, Filipe, Helder, Martin, Daniel, Maharajh, Amitaa, Garcia, Sara Mingo, De Neef, Mark, Lynch, Ceri, Howe, Gwenllian Sera, Singh, Jayaprakash, Turner, Keri, Ellis, Hannah, Stroud, Natalie, Cherian, Shiney, Cutler, Sean, Heron, Anne Emma, Roynon-Reed, Anna, Williams, Gemma, Richards, Owen, Cheema, Yusuf, Ahmad, Norfaizan, Barker, Joann, Bauchmuller, Kris, Bird, Sarah, Cawthron, Kay, Harrington, Kate, Jackson, Yvonne, Kibutu, Faith, Lenagh, Becky, Masuko, Shamiso, Raithatha, Ajay, Wiles, Matthew, Willson, Jayne, Newell, Helen, Lye, Alison, Nwafor, Lorenza, Jarman, Claire, Rowland-Jones, Sarah, Foote, David, Cole, Joby, Thompson, Roger, Watson, James, Hesseldon, Lisa, Macharia, Irene, Chetam, Luke, Smith, Jacqui, Ford, Amber, Anderson, Samantha, Birchall, Kathryn, Housley, Kay, Walker, Sara, Milner, Leanne, Hanratty, Helena, Trower, Helen, Phillips, Patrick, Oxspring, Simon, Donne, Ben, Bevan, Emily, Martin, Jane, Trodd, Dawn, Watson, Geoff, Brown, Caroline Wrey, Bunni, Lara, Jennings, Claire, Latif, Monica, Marshall, Rebecca, Subramanian, Gayathri, Bandla, Nageswar, Gellamucho, Minnie, Davies, Michelle, Thompson, Christopher, Trim, Fiona, Eapen, Beena, Ahmed, Cecilia, Baines, Balvinder, Clamp, Sarah, Colley, Julie, Haq, Risna, Hayes, Anne, Hulme, Jonathan, Hussain, Samia, Joseph, Sibet, Kumar, Rita, Maqsood, Zahira, Purewal, Manjit, Chandler, Ben, Elliott, Kerry, Mallinson, Janine, Turnbull, Alison, Dent, Kathy, Horsley, Elizabeth, Akhtar, Muhmmad Nauman, Pearson, Sandra, Potoczna, Dorota, Spencer, Sue, Blakemore, Hayley, Borislavova, Borislava, Faulkner, Beverley, Gendall, Emma, Goff, Elizabeth, Hayes, Kati, Thomas, Matt, Worner, Ruth, Smith, Kerry, Stephens, Deanna, Delgado, Carlos Castro, Dawson, Deborah, Ding, Lijun, Durrant, Georgia, Ezeobu, Obiageri, Farnell-Ward, Sarah, Harrison, Abiola, Kanu, Rebecca, Leaver, Susannah, Maccacari, Elena, Manna, Soumendu, Saluzzio, Romina Pepermans, Queiroz, Joana, Samakomva, Tinashe, Sicat, Christine, Texeira, Joana, Da Gloria, Edna Fernandes, Lisboa, Ana, Rawlins, John, Mathew, Jisha, Kinch, Ashley, Hurt, William James, Shah, Nirav, Clark, Victoria, Thanasi, Maria, Yun, Nikki, Patel, Kamal, Crickmore, Vikki, Debreceni, Gabor, Wilkins, Joy, Nicol, Liz, Burn, Iona, Hambrook, Geraldine, Manso, Katarina, Penn, Ruth, Shanmugasundaram, Pradeep, Tebbutt, Julie, Thornton, Danielle, Rostron, Anthony, Roy, Alistair, Woods, Lindsey, Cornell, Sarah, Wakinshaw, Fiona, Rogerson, Kimberley, Jarmain, Jordan, Anderson, Peter, Archer, Katie, Austin, Karen, Davis, Caroline, Durie, Alison, Kelsall, Olivia, Thrush, Jessica, Vigurs, Charlie, Wood, Hannah-Louise, Tranter, Helen, Harrison, Alison, Cowley, Nicholas, McAlindon, Michael, Digby, Stephen, Low, Emma, Morgan, Aled, Cother, Naiara, Rankin, Tobias, Clayton, Sarah, McCurdy, Alex, Allibone, Suzanne, Mary-Genetu, Roman, Patel, Amit, Mac, Ainhi, Murphy, Anthony, Mahjoob, Parisa, Nazari, Roonak, Worsley, Lucy, Fagan, Andrew, Mohamed Ali, Inthakab Ali, Beaumont, Karen, Blunt, Mark, Coton, Zoe, Curgenven, Hollie, Elsaadany, Mohamed, Fernandes, Kay, Ally, Sameena Mohamed, Rangarajan, Harini, Sarathy, Varun, Selvanayagam, Sivarupan, Vedage, Dave, White, Matthew, Fernandez-Roman, Jaime, Hamilton, David O., Johnson, Emily, Johnston, Brian, Martinez, Maria Lopez, Mulla, Suleman, Shaw, David, Waite, Alicia A. C., Waugh, Victoria, Welters, Ingeborg D., Williams, Karen, Bemand, Thomas, Black, Ethel, Rosa, Arnold Dela, Howle, Ryan, Jhanji, Shaman, Baikady, Ravishankar Rao, Tatham, Kate Colette, Thomas, Benjamin, Halkes, Matthew, Mercer, Pauline, Thornton, Lorraine, West, Joe, Baird, Tracy, Ruddy, Jim, Reece-Anthony, Rosie, Birt, Mark, Cowton, Amanda, Kay, Andrea, Kent, Melanie, Potts, Kathryn, Wilkinson, Ami, Naylor, Suzanne, Brown, Ellen, Clark, Michele, Purvis, Sarah, Cole, Jade, Davies, Rhys, Duffin, Donna, Hill, Helen, Player, Ben, Thomas, Emma, Williams, Angharad, Beith, Claire Marie, Black, Karen, Clements, Suzanne, Morrison, Alan, Strachan, Dominic, Taylor, Margaret, Clarkson, Michelle, D���Sylva, Stuart, Norman, Kathryn, Coventry, Tina, Fowler, Susan, McGregor, Amanda, Brady, Ailbhe, Chan, Rebekah, McIvor, Shane, Prady, Helena, Whittle, Helen, Mathew, Bijoy, Clapham, Melanie, Harper, Rosemary, Poultney, Una, Rice, Polly, Mutch, Rachel, Baird, Yolanda, Butler, Aaron, Chadbourn, Indra, Folkes, Linda, Fox, Heather, Gardner, Amy, Gomez, Raquel, Hobden, Gillian, King, Kirsten, Margarson, Michael, Martindale, Tim, Meadows, Emma, Raynard, Dana, Thirlwall, Yvette, Helm, David, Margalef, Jordi, Greer, Sandra, Shuker, Karen, Smuts, Sara, Duffield, Joseph, Smith, Oliver, Mallon, Lewis, Claire, Watkins, Birkinshaw, Isobel, Carter, Joseph, Howard, Kate, Ingham, Joanne, Joy, Rosie, Pearson, Harriet, Roche, Samantha, Scott, Zoe, Knights, Ellen, Price, Alicia, Thomas, Alice, Thorpe, Chris, Abraheem, Azmerelda, Bamford, Peter, Cawley, Kathryn, Dunmore, Charlie, Faulkner, Maria, Girach, Rumanah, Jeffrey, Helen, Jones, Rhianna, London, Emily, Nagra, Imrun, Nasir, Farah, Sainsbury, Hannah, Smedley, Clare, Khade, Reena, Sundar, Ashok, Tsinaslanidis, George, Behan, Teresa, Burnett, Caroline, Hatton, Jonathan, Heeney, Elaine, Mitra, Atideb, Newton, Maria, Pollard, Rachel, Stead, Rachael, Birch, Jenny, Bough, Laura, Goodsell, Josie, Tutton, Rebecca, Williams, Patricia, Williams, Sarah, Winter-Goodwin, Barbara, Auld, Fiona, Donnachie, Joanne, Edmond, Ian, Prentice, Lynn, Runciman, Nikole, Salutous, Dario, Symon, Lesley, Todd, Anne, Turner, Patricia, Short, Abigail, Sweeney, Laura, Murdoch, Euan, Senaratne, Dhaneesha, Burns, Karen, Higham, Andrew, Anderson, Taya, Hawcutt, Dan, O���Malley, Laura, Rad, Laura, Rogers, Naomi, Saunderson, Paula, Allison, Kathryn Sian, Afolabi, Deborah, Whitbread, Jennifer, Jones, Dawn, Dore, Rachael, Lankester, Liana, Nikitas, Nikitas, Wells, Colin, Stowe, Bethan, Spencer, Kayleigh, Cathcart, Susanne, Duffy, Katharine, Puxty, Alex, Puxty, Kathryn, Turner, Lynne, Ireland, Jane, Semple, Gary, Barry, Peter, Hilltout, Paula, Evitts, Jayne, Tyler, Amanda, Waldron, Joanne, Irvine, Val, Shelley, Benjamin, Akinkugbe, Olugbenga, Bamford, Alasdair, Beech, Emily, Belfield, Holly, Bell, Michael, Davies, Charlene, Jones, Gareth A. L., McHugh, Tara, Meghari, Hamza, O���Neill, Lauran, Peters, Mark J., Ray, Samiran, Tomas, Ana Luisa, Gorman, Claire, Gupta, Abhinav, Timlick, Elizabeth, Brady, Rebecca, Bonner, Stephen, Hugill, Keith, Jones, Jessica, Liggett, Steven, Bashyal, Archana, Davidson, Neil, Hutton, Paula, McKechnie, Stuart, Wilson, Jean, Flint, Neil, Rekha, Patel, Hales, Dawn, Cruz, Carina, Gopal, Shameer, Harris, Nichola, Lake, Victoria, Metherell, Stella, Radford, Elizabeth, Clement, Ian, Patel, Bijal, Gulati, A., Hays, Carole, Webster, K., Hudson, Anne, Webster, Andrea, Stephenson, Elaine, McCormack, Louise, Slater, Victoria, Nixon, Rachel, Hanson, Helen, Fearby, Maggie, Kelly, Sinead, Bridgett, Victoria, Robinson, Philip, Almaden-Boyle, Christine, Austin, Pauline, Cabrelli, Louise, Cole, Stephen, Casey, Matt, Chapman, Susan, Whyte, Clare, Brayne, Adam, Fisher, Emma, Hunt, Jane, Jackson, Peter, Kaye, Duncan, Love, Nicholas, Parkin, Juliet, Tuckey, Victoria, Van Koutrik, Lynne, Carter, Sasha, Andrew, Benedict, Findlay, Louise, Adams, Katie, Bruce, Michelle, Connolly, Karen, Duncan, Tracy, T.-Michael, Helen, Lindergard, Gabriella, Hey, Samuel, Fox, Claire, Alfonso, Jordan, Durrans, Laura Jayne, Guerin, Jacinta, Hruska, Martin, Eltayeb, Ayaa, Lamb, Thomas, Hodgkiss, Tracey, Cooper, Lisa, Rothwell, Joanne, Dennis, Catherine, McGregor, Alastair, Srikaran, Sinduya, Sukha, Anisha, Davies, Kim, O���Brien, Linda, Omar, Zohra, Perkins, Emma, Lewis, Tracy, Sutherland, Isobel, Brooke, Hollie, Buckley, Sarah, Suarez, Jose Cebrian, Charlesworth, Ruth, Hansson, Karen, Norris, John, Poole, Alice, Rose, Alastair, Sandhu, Rajdeep, Sloan, Brendan, Smithson, Elizabeth, Thirumaran, Muthu, Wagstaff, Veronica, Metcalfe, Alexandra, Camsooksai, Julie, Humphrey, Charlotte, Jenkins, Sarah, Wadams, Beverley, DeAth, Yasmin, Adams, Colene, Agasou, Anita, Arden, Tracie, Bowes, Amy, Boyle, Pauline, Beekes, Mandy, Button, Heather, Capps, Nigel, Carnahan, Mandy, Carter, Anne, Childs, Danielle, Donaldson, Denise, Hard, Kelly, Hurford, Fran, Hussain, Yasmin, Javaid, Ayesha, Jones, James, Jose, Sanal, Leigh, Michael, Martin, Terry, Millward, Helen, Motherwell, Nichola, Rikunenko, Rachel, Stickley, Jo, Summers, Julie, Ting, Louise, Tivenan, Helen, Tonks, Louise, Wilcox, Rebecca, Bokhari, Maria, Lucas, Rachael, McCormick, Wendy, Ritzema, Jenny, Sanderson, Amanda, Wild, Helen, Baxter, Nicola, Henderson, Steven, Kennedy-Hay, Sophie, McParland, Christopher, Rooney, Laura, Sim, Malcolm, McCreath, Gordan, Brunton, Mark, Caterson, Jess, Coles, Holly, Frise, Matthew, Rai, Sabi Gurung, Jacques, Nicola, Keating, Liza, Tilney, Emma, Bartley, Shauna, Bhuie, Parminder, Downes, Charlotte, Holding, Kathleen, Riches, Katie, Hilton, Mary, Hayman, Mel, Subramanian, Deepak, Daniel, Priya, Zitter, Letizia, Benyon, Sarah, Marriott, Suzie, Park, Linda, Keenan, Samantha, Gordon, Elizabeth, Quinn, Helen, Baines, Kizzy, Andrew, Gillian, Barclay, Lucy, Callaghan, Marie, Clark, Sarah, Hope, Dave, Marshall, Lucy, McCulloch, Corrienne, Briton, Kate, Singleton, Jo, Birch, Sophie, Simpson, Kerry, Craig, Jayne, Demetriou, Carrie, Eckbad, Charlotte, Hierons, Sarah, Howie, Lucy, Mitchard, Sarah, Ramos, Lidia, Serrano-Ruiz, Alfredo, White, Katie, Kelly, Fiona, Amin, Vishal, Anastasescu, Elena, Anumakonda, Vikram, Karthik, Komala, Kausar, Rizwana, Reid, Karen, Smith, Jacqueline, Imeson-Wood, Janet, Bellini, Arianna, Bryant, Jade, Mayer, Anton, Pickard, Amy, Roe, Nicholas, Sowter, Jason, Howlett, Alex, Criste, Kristine, Cusack, Rebecca, Golder, Kim, Golding, Hannah, Jones, Oliver, Leggett, Samantha, Male, Michelle, Marani, Martyna, Prager, Kirsty, Williams, Toran, Roberts, Belinda, Salmon, Karen, Gondo, Prisca, Hadebe, B., Kayani, Abdul, Masunda, Bridgett, Ahmed, Ashar, Morris, Anna, Jakkula, Srinivas, Long, Kate, Whiteley, Simon, Wilby, Elizabeth, Ogg, Bethan, Moultrie, Sam, Odam, M., Bewley, Jeremy, Garland, Zoe, Grimmer, Lisa, Gumbrill, Bethany, Johnson, Rebekah, Sweet, Katie, Webster, Denise, Efford, Georgia, Bennett, Sara, Goodwin, Emma, Jackson, Matthew, Kent, Alissa, Tibke, Clare, Woodyatt, Wiesia, Zaki, Ahmed, Daniel, Amelia, Finn, Joanne, Saha, Rajnish, Bremmer, Pamela, Allan, J., Geary, T., Houston, Gordon, Meikle, A., O���Brien, P., Bell, Dina, Boyle, Rosalind, Douglas, Katie, Glass, Lynn, Lee, Emma, Lennon, Liz, Rattray, Austin, Charnock, Rob, McFarland, Denise, Cosgrove, Denise, Attwood, Ben, Parsons, Penny, Carmody, Siobhain, Oblak, Metod, Popescu, Monica, Thankachen, Mini, Baruah, Rosie, Morris, Sheila, Ferguson, Susie, Shepherd, Amy, Altabaibeh, Abdelhakim, Alvaro, Ana, Gilbert, Kayleigh, Ma, Louise, Mostoles, Loreta, Parmar, Chetan, Simpson, Kathryn, Jetha, Champa, Booker, Lauren, Pratley, Anezka, Cosier, Tracey, Millen, Gemma, Schumacher, Natasha, Weston, Heather, Rand, James, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S., Bogaert, Debby, Chand, Meera, Cooke, Graham S., Docherty, Annemarie B., Dunning, Jake, Da Silva Filipe, Ana, Fletcher, Tom, Green, Christoper A., Harrison, Ewen M., Hiscox, Julian A., Ijaz, Samreen, Khoo, Saye, Lim, Wei Shen, Mentzer, Alexander J., Merson, Laura, Noursadeghi, Mahdad, Moore, Shona C., Palmarini, Massimo, Paxton, William A., Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L., Sancho-Shimizu, Vanessa, Scott, Janet T., De Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Tedder, Richard S., Thomson, Emma C., Roger Thompson, A. A., Thwaites, Ryan S., Turtle, Lance C. W., Gupta, Rishi K., Palmieri, Carlo, Swann, Olivia V., Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian L., Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petros, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew R., Correia, Gon��alo Dos Santos, Sands, Caroline J., Takis, Panteleimon, Maslen, Lynn, Greenhalf, William, Shaw, Victoria, McDonald, Sarah E., Keating, Se��n, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin W. A., Clark, Jordan J., Clarke, Emily A., Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W. S., Foster, Terry, Garcia-Dorival, Isabel, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S., Middleton, Joanna, Mitchell, Joyce, Murphy, Ellen G., Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E., Shears, Rebecca K., Small, Benjamin, Subramaniam, Krishanthi S., Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, Van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, McCafferty, Sarah, Morrice, Kirstie, MacLean, Alan, Armstrong, Ruth, Boz, Ceilia, Brown, Adam, Coutts, Audrey, Cullum, Louise, Day, Nicky, Donnelly, Lorna, Duncan, Esther, Fawkes, Angie, Finernan, Paul, Gilchrist, Tammy, Golightly, Ailsa, Hafezi, Katarzyna, Law, Dawn, Law, Rachel, Law, Sarah, Macgillivray, Louise, Maclean, Alan, Mal, Hanning, Mcmaster, Ellie, Meikle, Jen, Oosthuyzen, Wilna, Paterson, Trevor, Stenhouse, Andrew, Swets, Maaike, Szoor-McElhinney, Helen, Taneski, Filip, Wackett, Tony, Ward, Mairi, Weaver, Jane, Coyle, Judy, Gallagher, Bernadette, Lidstone-Scott, Rebecca, Hamilton, Debbie, Schon, Katherine, Furlong, Anita, Biggs, Heather, Griffiths, Fiona, Andrews, Eleanor, Brickell, Kathy, Smyth, Michelle, Murphy, Lorna, Carson, Gail, Hardwick, Hayley, and Donohue, Chloe
- Subjects
631/208 ,692/699/255/2514 ,631/208/205/2138 ,45/43 ,article ,631/326/596/4130 ,3. Good health - Abstract
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191, 2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3���7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
50. GWAS meta-analysis (N=279,930) identifies new genes and functional links to general cognitive ability
- Author
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Savage, Jeanne E., Jansen, Philip R., Stringer, Sven, Watanabe, Kyoko, Bryois, Julien, Leeuw, Christiaan A., Nagel, Mats, Awasthi, Swapnil, Barr, Peter B., Coleman, Jonathan R. I., Grasby, Katrina L., Hammerschlag, Anke R., Kaminski, Jakob, Karlsson, Robert, Krapohl, Eva, Lam, Max, Nygaard, Marianne, Reynolds, Chandra A., Trampush, Joey W., Young, Hannah, Zabaneh, Delilah, Hagg, Sara, Hansell, Narelle K., Karlsson, Ida K., Linnarsson, Sten, Montgomery, Grant W., Munoz-Manchado, Ana B., Quinlan, Erin B., Schumann, Gunter, Skene, Nathan, Webb, Bradley T., White, Tonya, Arking, Dan E., Attix, Deborah K., Avramopoulos, Dimitrios, Bilder, Robert M., Bitsios, Panos, Burdick, Katherine E., Cannon, Tyrone D., Chiba-Falek, Ornit, Christoforou, Andrea, Cirulli, Elizabeth T., Congdon, Eliza, Corvin, Aiden, Davies, Gail, Deary, Ian J., Derosse, Pamela, Dickinson, Dwight, Djurovic, Srdjan, Donohoe, Gary, Conley, Emily Drabant, Eriksson, Johan G., Espeseth, Thomas, Freimer, Nelson A., Giakoumaki, Stella, Giegling, Ina, Gill, Michael, Glahn, David C., Hariri, Ahmad R., Hatzimanolis, Alex, Keller, Matthew C., Knowles, Emma, Konte, Bettina, Lahti, Jari, Le Hellard, Stephanie, Lencz, Todd, Liewald, David C., London, Edythe, Lundervold, Astri J., Malhotra, Anil K., Melle, Ingrid, Morris, Derek, Need, Anna C., Ollier, William, Palotie, Aarno, Payton, Antony, Pendleton, Neil, Poldrack, Russell A., Raikkonen, Katri, Reinvang, Ivar, Roussos, Panos, Rujescu, Dan, Sabb, Fred W., Scult, Matthew A., Smeland, Olav B., Smyrnis, Nikolaos, Starr, John M., Steen, Vidar M., Stefanis, Nikos C., Straub, Richard E., Sundet, Kjetil, Voineskos, Aristotle N., Weinberger, Daniel R., Widen, Elisabeth, Yu, Jin, Abecasis, Goncalo, Andreassen, Ole A., Breen, Gerome, Christiansen, Lene, Debrabant, Birgit, Dick, Danielle M., Heinz, Andreas, Hjerling-Leffler, Jens, Ikram, M. Arfan, Kendler, Kenneth S., Martin, Nicholas G., Medland, Sarah E., Pedersen, Nancy L., Plomin, Robert, Polderman, Tinca J. C., Ripke, Stephan, Sluis, Sophie, Sullivan, Patrick F., Tiemeier, Henning, Vrieze, Scott I., Margaret Wright, and Posthuma, Danielle
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