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503 results on '"Purcell, Shaun M"'

1. Study Protocol: Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project

Author: Wang, Jun, Jiang, Chenguang, Guo, Zhenglin, Chapman, Sinéad, Kozhemiako, Nataliia, Mylonas, Dimitrios, Su, Yi, Zhou, Lin, Shen, Lu, Qin, Shengying, Murphy, Michael, Tan, Shuping, Manoach, Dara S., Stickgold, Robert, Huang, Hailiang, Zhou, Zhenhe, Purcell, Shaun M., Hall, Meihua, Hyman, Steven E., and Pan, Jen Q.
Published: 2024
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2. A Potential Source of Bias in Group-Level EEG Microstate Analysis

Author: Murphy, Michael, Wang, Jun, Jiang, Chenguang, Wang, Lei A., Kozhemiako, Nataliia, Wang, Yining, Pan, Jen Q., and Purcell, Shaun M.
Published: 2024
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3. Electroencephalographic Microstates During Sleep and Wake in Schizophrenia

Author: Wang, Jun, Jiang, Chenguang, Gai, Guanchen, Zou, Kai, Wang, Zhe, Yu, Xiaoman, Wang, Guoqiang, Tan, Shuping, Murphy, Michael, Hall, Mei Hua, Zhu, Wei, Zhou, Zhenhe, Shen, Lu, Qin, Shenying, Huang, Hailiang, Kozhemiako, Nataliia, Wang, Lei A., Wang, Yining, Zhou, Lin, Li, Shen, Law, Robert, Mylonas, Minitrios, Stickgold, Robert, Manoach, Dara, Hall, Mei-Hua, Pan, Jen Q., Purcell, Shaun M., Guo, Zhenglin, Chapman, Sinead, and Jiang, Chenaugnag
Published: 2024
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4. Upregulated heme biosynthesis increases obstructive sleep apnea severity: a pathway-based Mendelian randomization study

Author: Wang, Heming, Kurniansyah, Nuzulul, Cade, Brian E, Goodman, Matthew O, Chen, Han, Gottlieb, Daniel J, Gharib, Sina A, Purcell, Shaun M, Lin, Xihong, Saxena, Richa, Zhu, Xiaofeng, Durda, Peter, Tracy, Russel, Liu, Yongmei, Taylor, Kent D, Johnson, W Craig, Gabriel, Stacey, Smith, Joshua D, Aguet, François, Ardlie, Kirstin, Blackwell, Tom, Reiner, Alexander P, Rotter, Jerome I, Rich, Stephen S, Redline, Susan, and Sofer, Tamar
Subjects: Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Cardiovascular Medicine and Haematology, Health Sciences, Human Genome, Lung, Sleep Research, 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Good Health and Well Being, Aged, Datasets as Topic, Female, Genetic Predisposition to Disease, Heme, Humans, Iron, Male, Mendelian Randomization Analysis, Metabolic Networks and Pathways, Middle Aged, Polysomnography, Quantitative Trait Loci, Severity of Illness Index, Sleep Apnea, Obstructive, Up-Regulation, TOPMed Sleep Traits Working Group
Abstract: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Iron and heme metabolism, implicated in ventilatory control and OSA comorbidities, was associated with OSA phenotypes in recent admixture mapping and gene enrichment analyses. However, its causal contribution was unclear. In this study, we performed pathway-level transcriptional Mendelian randomization (MR) analysis to investigate the causal relationships between iron and heme related pathways and OSA. In primary analysis, we examined the expression level of four iron/heme Reactome pathways as exposures and four OSA traits as outcomes using cross-tissue cis-eQTLs from the Genotype-Tissue Expression portal and published genome-wide summary statistics of OSA. We identify a significant putative causal association between up-regulated heme biosynthesis pathway with higher sleep time percentage of hypoxemia (p = 6.14 × 10-3). This association is supported by consistency of point estimates in one-sample MR in the Multi-Ethnic Study of Atherosclerosis using high coverage DNA and RNA sequencing data generated by the Trans-Omics for Precision Medicine project. Secondary analysis for 37 additional iron/heme Gene Ontology pathways did not reveal any significant causal associations. This study suggests a causal association between increased heme biosynthesis and OSA severity.
Published: 2022

5. Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program

Author: Cade, Brian E, Lee, Jiwon, Sofer, Tamar, Wang, Heming, Zhang, Man, Chen, Han, Gharib, Sina A, Gottlieb, Daniel J, Guo, Xiuqing, Lane, Jacqueline M, Liang, Jingjing, Lin, Xihong, Mei, Hao, Patel, Sanjay R, Purcell, Shaun M, Saxena, Richa, Shah, Neomi A, Evans, Daniel S, Hanis, Craig L, Hillman, David R, Mukherjee, Sutapa, Palmer, Lyle J, Stone, Katie L, Tranah, Gregory J, Abecasis, Gonçalo R, Boerwinkle, Eric A, Correa, Adolfo, Cupples, L Adrienne, Kaplan, Robert C, Nickerson, Deborah A, North, Kari E, Psaty, Bruce M, Rotter, Jerome I, Rich, Stephen S, Tracy, Russell P, Vasan, Ramachandran S, Wilson, James G, Zhu, Xiaofeng, and Redline, Susan
Subjects: Biological Sciences, Genetics, Sleep Research, Dental/Oral and Craniofacial Disease, Lung, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Alleles, Chromatin Immunoprecipitation Sequencing, Female, Gene Expression Regulation, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, National Heart, Lung, and Blood Institute (U.S.), Phenotype, Precision Medicine, Research, Signal Transduction, Sleep Apnea Syndromes, United States, Whole Genome Sequencing, Sleep-disordered breathing, Sleep apnea, Whole-genome sequencing, WGS, Genome-wide association study, GWAS, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Sleep Working Group, Clinical Sciences
Abstract: BackgroundSleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.MethodsThe study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation
Published: 2021

6. Macro and micro sleep architecture and cognitive performance in older adults

Author: Djonlagic, Ina, Mariani, Sara, Fitzpatrick, Annette L, Van Der Klei, Veerle MGTH, Johnson, Dayna A, Wood, Alexis C, Seeman, Teresa, Nguyen, Ha T, Prerau, Michael J, Luchsinger, José A, Dzierzewski, Joseph M, Rapp, Stephen R, Tranah, Gregory J, Yaffe, Kristine, Burdick, Katherine E, Stone, Katie L, Redline, Susan, and Purcell, Shaun M
Subjects: Biological Psychology, Psychology, Basic Behavioral and Social Science, Sleep Research, Clinical Research, Neurosciences, Aging, Behavioral and Social Science, Age Factors, Aged, Aged, 80 and over, Case-Control Studies, Cognition, Electroencephalography, Humans, Male, Metabolic Syndrome, Middle Aged, Sleep, Sleep, REM, Biomedical and clinical sciences, Health sciences
Abstract: We sought to determine which facets of sleep neurophysiology were most strongly linked to cognitive performance in 3,819 older adults from two independent cohorts, using whole-night electroencephalography. From over 150 objective sleep metrics, we identified 23 that predicted cognitive performance, and processing speed in particular, with effects that were broadly independent of gross changes in sleep quality and quantity. These metrics included rapid eye movement duration, features of the electroencephalography power spectra derived from multivariate analysis, and spindle and slow oscillation morphology and coupling. These metrics were further embedded within broader associative networks linking sleep with aging and cardiometabolic disease: individuals who, compared with similarly aged peers, had better cognitive performance tended to have profiles of sleep metrics more often seen in younger, healthier individuals. Taken together, our results point to multiple facets of sleep neurophysiology that track coherently with underlying, age-dependent determinants of cognitive and physical health trajectories in older adults.
Published: 2021

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

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

Author: Bigdeli, Tim B, Genovese, Giulio, Georgakopoulos, Penelope, Meyers, Jacquelyn L, Peterson, Roseann E, Iyegbe, Conrad O, Medeiros, Helena, Valderrama, Jorge, Achtyes, Eric D, Kotov, Roman, Stahl, Eli A, Abbott, Colony, Azevedo, Maria Helena, Belliveau, Richard A, Bevilacqua, Elizabeth, Bromet, Evelyn J, Byerley, William, Carvalho, Celia Barreto, Chapman, Sinéad B, DeLisi, Lynn E, Dumont, Ashley L, O’Dushlaine, Colm, Evgrafov, Oleg V, Fochtmann, Laura J, Gage, Diane, Kennedy, James L, Kinkead, Becky, Macedo, Antonio, Moran, Jennifer L, Morley, Christopher P, Dewan, Mantosh J, Nemesh, James, Perkins, Diana O, Purcell, Shaun M, Rakofsky, Jeffrey J, Scolnick, Edward M, Sklar, Brooke M, Sklar, Pamela, Smoller, Jordan W, Sullivan, Patrick F, Macciardi, Fabio, Marder, Stephen R, Gur, Ruben C, Gur, Raquel E, Braff, David L, Nicolini, Humberto, Escamilla, Michael A, Vawter, Marquis P, Sobell, Janet L, Malaspina, Dolores, Lehrer, Douglas S, Buckley, Peter F, Rapaport, Mark H, Knowles, James A, Fanous, Ayman H, Pato, Michele T, McCarroll, Steven A, and Pato, Carlos N
Subjects: Human Genome, Serious Mental Illness, Clinical Research, Schizophrenia, Brain Disorders, Genetics, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Black People, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Male, Polymorphism, Single Nucleotide, Consortium on the Genetics of Schizophrenia (COGS) Investigators, Genomic Psychiatry Cohort (GPC) Consortium, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke's R2 = 0.032; liability R2 = 0.017; P
Published: 2020

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

Author: Ripke, Stephan, Neale, Benjamin M., Corvin, Aiden, Walters, James T.R., Farh, Kai-How, Holmans, Peter A., Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Belliveau, Richard A., Jr., Bene, Judit, Bergen, Sarah E., Bevilacqua, Elizabeth, Bigdeli, Tim B., Black, Donald W., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Catts, Stanley V., Chambert, Kimberley D., Chan, Raymond C.K., Chan, Ronald Y.L., Chen, Eric Y.H., Cheng, Wei, Cheung, Eric FC., Chong, Siow Ann, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J., Curtis, David, Davidson, Michael, Davis, Kenneth L., Degenhardt, Franziska, Del Favero, Jurgen, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H., Farrell, Martilias S., Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B., Friedl, Marion, Friedman, Joseph I., Fromer, Menachem, Genovese, Giulio, Georgieva, Lyudmila, Giegling, Ina, Giusti-Rodríguez, Paola, Godard, Stephanie, Goldstein, Jacqueline I., Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, de Haan, Lieuwe, Hammer, Christian, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Henskens, Frans A., Herms, Stefan, Hirschhorn, Joel N., Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V., Hougaard, David M., Ikeda, Masashi, Joa, Inge, Julià, Antonio, Kahn, René S., Kalaydjieva, Luba, Karachanak-Yankova, Sena, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C., Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Klovins, Janis, Knowles, James A., Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Kähler, Anna K., Laurent, Claudine, Lee, Jimmy, Lee, S. Hong, Legge, Sophie E., Lerer, Bernard, Li, Miaoxin, Li, Tao, Liang, Kung-Yee, Lieberman, Jeffrey, Limborska, Svetlana, Loughland, Carmel M., Lubinski, Jan, Lönnqvist, Jouko, Macek, Milan, Magnusson, Patrik K.E., Maher, Brion S., Maier, Wolfgang, Mallet, Jacques, Marsal, Sara, Mattheisen, Manuel, Mattingsdal, Morten, McCarley, Robert W., McDonald, Colm, McIntosh, Andrew M., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mokrab, Younes, Morris, Derek W., Mors, Ole, Murphy, Kieran C., Murray, Robin M., Myin-Germeys, Inez, Müller-Myhsok, Bertram, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, O'Callaghan, Eadbhard, O'Dushlaine, Colm, O'Neill, F. Anthony, Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Van Os, Jim, Pantelis, Christos, Papadimitriou, George N., Papiol, Sergi, Parkhomenko, Elena, Pato, Michele T., Paunio, Tiina, Pejovic-Milovancevic, Milica, Perkins, Diana O., Pietiläinen, Olli, Pimm, Jonathan, Pocklington, Andrew J., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Rasmussen, Henrik B., Reichenberg, Abraham, Reimers, Mark A., Richards, Alexander L., Roffman, Joshua L., Roussos, Panos, Ruderfer, Douglas M., Salomaa, Veikko, Sanders, Alan R., Schall, Ulrich, Schubert, Christian R., Schulze, Thomas G., Schwab, Sibylle G., Scolnick, Edward M., Scott, Rodney J., Seidman, Larry J., Shi, Jianxin, Sigurdsson, Engilbert, Silagadze, Teimuraz, Silverman, Jeremy M., Sim, Kang, Slominsky, Petr, Smoller, Jordan W., So, Hon-Cheong, Spencer, Chris C.A., Stahl, Eli A., Stefansson, Hreinn, Steinberg, Stacy, Stogmann, Elisabeth, Straub, Richard E., Strengman, Eric, Strohmaier, Jana, Stroup, T Scott, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Söderman, Erik, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Veijola, Juha, Waddington, John, Walsh, Dermot, Wang, Dai, Wang, Qiang, Webb, Bradley T., Weiser, Mark, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wormley, Brandon K., Xi, Hualin Simon, Zai, Clement C., Zheng, Xuebin, Zimprich, Fritz, Wray, Naomi R., Stefansson, Kari, Visscher, Peter M., Adolfsson, Rolf, Andreassen, Ole A., Blackwood, Douglas H.R., Bramon, Elvira, Buxbaum, Joseph D., Børglum, Anders D., Cichon, Sven, Darvasi, Ariel, Domenici, Enrico, Ehrenreich, Hannelore, Esko, Tõnu, Gejman, Pablo V., Gill, Michael, Gurling, Hugh, Hultman, Christina M., Iwata, Nakao, Jablensky, Assen V., Jönsson, Erik G., Kendler, Kenneth S., Kirov, George, Knight, Jo, Lencz, Todd, Levinson, Douglas F., Li, Qingqin S., Liu, Jianjun, Malhotra, Anil K., McCarroll, Steven A., McQuillin, Andrew, Moran, Jennifer L., Mortensen, Preben B., Mowry, Bryan J., Nöthen, Markus M., Ophoff, Roel A., Owen, Michael J., Palotie, Aarno, Pato, Carlos N., Petryshen, Tracey L., Posthuma, Danielle, Rietschel, Marcella, Riley, Brien P., Rujescu, Dan, Sham, Pak C., Sklar, Pamela, St Clair, David, Weinberger, Daniel R., Wendland, Jens R., Werge, Thomas, Daly, Mark J., Sullivan, Patrick F., O'Donovan, Michael C., Qin, Shengying, Sawa, Akira, Kahn, Rene, Hong, Kyung Sue, Shi, Wenzhao, Tsuang, Ming, Itokawa, Masanari, Feng, Gang, Glatt, Stephen J., Ma, Xiancang, Tang, Jinsong, Ruan, Yunfeng, Liu, Ruize, Zhu, Feng, Horiuchi, Yasue, Lee, Byung Dae, Joo, Eun-Jeong, Myung, Woojae, Ha, Kyooseob, Won, Hong-Hee, Baek, Ji Hyung, Chung, Young Chul, Kim, Sung-Wan, Kusumawardhani, Agung, Chen, Wei J., Hwu, Hai-Gwo, Hishimoto, Akitoyo, Otsuka, Ikuo, Sora, Ichiro, Toyota, Tomoko, Yoshikawa, Takeo, Kunugi, Hiroshi, Hattori, Kotaro, Ishiwata, Sayuri, Numata, Shusuke, Ohmori, Tetsuro, Arai, Makoto, Ozeki, Yuji, Fujii, Kumiko, Kim, Se Joo, Lee, Heon-Jeong, Ahn, Yong Min, Kim, Se Hyun, Akiyama, Kazufumi, Shimoda, Kazutaka, Kinoshita, Makoto, Hsu, Yu-Han H., Pintacuda, Greta, Nacu, Eugeniu, Kim, April, Tsafou, Kalliopi, Petrossian, Natalie, Crotty, William, Suh, Jung Min, Riseman, Jackson, Martin, Jacqueline M., Biagini, Julia C., Mena, Daya, Ching, Joshua K.T., Malolepsza, Edyta, Li, Taibo, Singh, Tarjinder, Ge, Tian, Egri, Shawn B., Tanenbaum, Benjamin, Stanclift, Caroline R., Apffel, Annie M., Carr, Steven A., Schenone, Monica, Jaffe, Jake, Fornelos, Nadine, Eggan, Kevin C., and Lage, Kasper
Published: 2023
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10. Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases

Author: Charney, Alexander W, Stahl, Eli A, Green, Elaine K, Chen, Chia-Yen, Moran, Jennifer L, Chambert, Kimberly, Belliveau, Richard A, Forty, Liz, Gordon-Smith, Katherine, Lee, Phil H, Bromet, Evelyn J, Buckley, Peter F, Escamilla, Michael A, Fanous, Ayman H, Fochtmann, Laura J, Lehrer, Douglas S, Malaspina, Dolores, Marder, Stephen R, Morley, Christopher P, Nicolini, Humberto, Perkins, Diana O, Rakofsky, Jeffrey J, Rapaport, Mark H, Medeiros, Helena, Sobell, Janet L, Backlund, Lena, Bergen, Sarah E, Juréus, Anders, Schalling, Martin, Lichtenstein, Paul, Knowles, James A, Burdick, Katherine E, Jones, Ian, Jones, Lisa A, Hultman, Christina M, Perlis, Roy, Purcell, Shaun M, McCarroll, Steven A, Pato, Carlos N, Pato, Michele T, Di Florio, Ariana, Craddock, Nick, Landén, Mikael, Smoller, Jordan W, Ruderfer, Douglas M, and Sklar, Pamela
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Genetics, Serious Mental Illness, Bipolar Disorder, Mental Health, Prevention, Brain Disorders, Schizophrenia, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Case-Control Studies, Cohort Studies, DNA Copy Number Variations, Gene Duplication, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Psychotic Disorders, Bipolar disorder, Copy number variant, Polygenic risk score, Rare variant burden, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences, Psychology
Abstract: BackgroundGenetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.MethodsRare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.ResultsCNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.ConclusionsCNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
Published: 2019

11. Admixture mapping identifies novel loci for obstructive sleep apnea in Hispanic/Latino Americans

Author: Wang, Heming, Cade, Brian E, Sofer, Tamar, Sands, Scott A, Chen, Han, Browning, Sharon R, Stilp, Adrienne M, Louie, Tin L, Thornton, Timothy A, Johnson, W Craig, Below, Jennifer E, Conomos, Matthew P, Evans, Daniel S, Gharib, Sina A, Guo, Xiuqing, Wood, Alexis C, Mei, Hao, Yaffe, Kristine, Loredo, Jose S, Ramos, Alberto R, Barrett-Connor, Elizabeth, Ancoli-Israel, Sonia, Zee, Phyllis C, Arens, Raanan, Shah, Neomi A, Taylor, Kent D, Tranah, Gregory J, Stone, Katie L, Hanis, Craig L, Wilson, James G, Gottlieb, Daniel J, Patel, Sanjay R, Rice, Ken, Post, Wendy S, Rotter, Jerome I, Sunyaev, Shamil R, Cai, Jianwen, Lin, Xihong, Purcell, Shaun M, Laurie, Cathy C, Saxena, Richa, Redline, Susan, and Zhu, Xiaofeng
Subjects: Biological Sciences, Genetics, Sleep Research, Lung, Aged, Chromosome Mapping, Female, Ferrochelatase, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Polysomnography, Sleep Apnea, Obstructive, White People, Medical and Health Sciences, Genetics & Heredity
Abstract: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk of cardiovascular disease and mortality. Its prevalence and severity vary across ancestral background. Although OSA traits are heritable, few genetic associations have been identified. To identify genetic regions associated with OSA and improve statistical power, we applied admixture mapping on three primary OSA traits [the apnea hypopnea index (AHI), overnight average oxyhemoglobin saturation (SaO2) and percentage time SaO2
Published: 2019

12. Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep

Author: Cade, Brian E, Chen, Han, Stilp, Adrienne M, Louie, Tin, Ancoli-Israel, Sonia, Arens, Raanan, Barfield, Richard, Below, Jennifer E, Cai, Jianwen, Conomos, Matthew P, Evans, Daniel S, Frazier-Wood, Alexis C, Gharib, Sina A, Gleason, Kevin J, Gottlieb, Daniel J, Hillman, David R, Johnson, W Craig, Lederer, David J, Lee, Jiwon, Loredo, Jose S, Mei, Hao, Mukherjee, Sutapa, Patel, Sanjay R, Post, Wendy S, Purcell, Shaun M, Ramos, Alberto R, Reid, Kathryn J, Rice, Ken, Shah, Neomi A, Sofer, Tamar, Taylor, Kent D, Thornton, Timothy A, Wang, Heming, Yaffe, Kristine, Zee, Phyllis C, Hanis, Craig L, Palmer, Lyle J, Rotter, Jerome I, Stone, Katie L, Tranah, Gregory J, Wilson, James G, Sunyaev, Shamil R, Laurie, Cathy C, Zhu, Xiaofeng, Saxena, Richa, Lin, Xihong, and Redline, Susan
Subjects: Genetics, Lung, Sleep Research, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Aged, Aged, 80 and over, Cell Adhesion Molecules, Neuronal, Computational Biology, Extracellular Matrix Proteins, Female, Gene Regulatory Networks, Genetic Variation, Genome-Wide Association Study, Hexokinase, Humans, Hypoxia, Interleukin-18 Receptor alpha Subunit, Male, Middle Aged, NLR Family, Pyrin Domain-Containing 3 Protein, Nerve Tissue Proteins, Oxygen, Oxyhemoglobins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reelin Protein, Serine Endopeptidases, Sleep, Sleep Apnea Syndromes, Young Adult, Developmental Biology
Abstract: Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
Published: 2019

13. Evaluation of an automated pipeline for large-scale EEG spectral analysis: the National Sleep Research Resource

Author: Mariani, Sara, Tarokh, Leila, Djonlagic, Ina, Cade, Brian E, Morrical, Michael G, Yaffe, Kristine, Stone, Katie L, Loparo, Kenneth A, Purcell, Shaun M, Redline, Susan, and Aeschbach, Daniel
Subjects: Medical Physiology, Biomedical and Clinical Sciences, Clinical Research, Sleep Research, Aged, Cohort Studies, Electroencephalography, Female, Humans, Polysomnography, Sensitivity and Specificity, Signal Processing, Computer-Assisted, Sleep, Sleep Stages, Sleep, REM, Large-scale spectral analysis, Sleep EEG, Artifact detection, Clinical Sciences, Psychology, Neurology & Neurosurgery, Clinical sciences, Clinical and health psychology
Abstract: Study objectivesWe present an automated sleep electroencephalogram (EEG) spectral analysis pipeline that includes an automated artifact detection step, and we test the hypothesis that spectral power density estimates computed with this pipeline are comparable to those computed with a commercial method preceded by visual artifact detection by a sleep expert (standard approach).MethodsEEG data were analyzed from the C3-A2 lead in a sample of polysomnograms from 161 older women participants in a community-based cohort study. We calculated the sensitivity, specificity, accuracy, and Cohen's kappa measures from epoch-by-epoch comparisons of automated to visual-based artifact detection results; then we computed the average EEG spectral power densities in six commonly used EEG frequency bands and compared results from the two methods using correlation analysis and Bland-Altman plots.ResultsAssessment of automated artifact detection showed high specificity [96.8%-99.4% in non-rapid eye movement (NREM), 96.9%-99.1% in rapid eye movement (REM) sleep] but low sensitivity (26.7%-38.1% in NREM, 9.1-27.4% in REM sleep). However, large artifacts (total power > 99th percentile) were removed with sensitivity up to 87.7% in NREM and 90.9% in REM, with specificities of 96.9% and 96.6%, respectively. Mean power densities computed with the two approaches for all EEG frequency bands showed very high correlation (≥0.99). The automated pipeline allowed for a 100-fold reduction in analysis time with regard to the standard approach.ConclusionDespite low sensitivity for artifact rejection, the automated pipeline generated results comparable to those obtained with a standard method that included manual artifact detection. Automated pipelines can enable practical analyses of recordings from thousands of individuals, allowing for use in genetics and epidemiological research requiring large samples.
Published: 2018

14. The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls

Author: Byrne, Enda M., Forstner, Andreas J., Holmans, Peter A., de Leeuw, Christiaan A., Mattheisen, Manuel, McQuillin, Andrew, Whitehead Pavlides, Jennifer M., Pers, Tune H., Ripke, Stephan, Stahl, Eli A., Steinberg, Stacy, Trubetskoy, Vassily, Trzaskowski, Maciej, Wang, Yunpeng, Abbott, Liam, Abdellaoui, Abdel, Adams, Mark J., Adolfsson, Annelie Nordin, Agerbo, Esben, Akil, Huda, Albani, Diego, Alliey-Rodriguez, Ney, Als, Thomas D., Andlauer, Till F.M., Anjorin, Adebayo, Antilla, Verneri, Van der Auwera, Sandra, Awasthi, Swapnil, Bacanu, Silviu-Alin, Badner, Judith A., Bækvad-Hansen, Marie, Barchas, Jack D., Bass, Nicholas, Bauer, Michael, Beekman, Aartjan T.F., Belliveau, Richard, Bergen, Sarah E., Bigdeli, Tim B., Binder, Elisabeth B., Bøen, Erlend, Boks, Marco, Boocock, James, Budde, Monika, Bunney, William, Burmeister, Margit, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Byerley, William, Cai, Na, Casas, Miquel, Castelao, Enrique, Cerrato, Felecia, Cervantes, Pablo, Chambert, Kimberly, Charney, Alexander W., Chen, Danfeng, Christensen, Jane Hvarregaard, Churchhouse, Claire, St Clair, David, Clarke, Toni-Kim, Colodro-Conde, Lucía, Coryell, William, Couvy-Duchesne, Baptiste, Craig, David W., Crawford, Gregory E., Cruceanu, Cristiana, Czerski, Piotr M., Dale, Anders M., Davies, Gail, Deary, Ian J., Degenhardt, Franziska, Del-Favero, Jurgen, DePaulo, J Raymond, Derks, Eske M., Direk, Nese, Djurovic, Srdjan, Dobbyn, Amanda L., Dolan, Conor V., Dumont, Ashley, Dunn, Erin C., Eley, Thalia C., Elvsåshagen, Torbjørn, Escott-Price, Valentina, Fan, Chun Chieh, Finucane, Hilary K., Fischer, Sascha B., Flickinger, Matthew, Foo, Jerome C., Foroud, Tatiana M., Forty, Liz, Frank, Josef, Fraser, Christine, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Gage, Diane, Garnham, Julie, Giambartolomei, Claudia, Goes, Fernando S., Goldstein, Jaqueline, Gordon, Scott D., Gordon-Smith, Katherine, Green, Elaine K., Green, Melissa J., Greenwood, Tiffany A., Grove, Jakob, Guan, Weihua, Hall, Lynsey S., Hamshere, Marian L., Hansen, Christine Søholm, Hansen, Thomas F., Hautzinger, Martin, Heilbronner, Urs, van Hemert, Albert M., Herms, Stefan, Hickie, Ian B., Hipolito, Maria, Hoffmann, Per, Holland, Dominic, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Huckins, Laura, Ising, Marcus, Jamain, Stéphane, Jansen, Rick, Johnson, Jessica S., de Jong, Simone, Jorgenson, Eric, Juréus, Anders, Kandaswamy, Radhika, Karlsson, Robert, Kennedy, James L., Hassan Kiadeh, Farnush Farhadi, Kittel-Schneider, Sarah, Knowles, James A., Kogevinas, Manolis, Kohane, Isaac S., Koller, Anna C., Kraft, Julia, Kretzschmar, Warren W., Krogh, Jesper, Kupka, Ralph, Kutalik, Zoltán, Lavebratt, Catharina, Lawrence, Jacob, Lawson, William B., Leber, Markus, Lee, Phil H., Levy, Shawn E., Li, Jun Z., Li, Yihan, Lind, Penelope A., Liu, Chunyu, Olde Loohuis, Loes M., Maaser, Anna, MacIntyre, Donald J., MacKinnon, Dean F., Mahon, Pamela B., Maier, Wolfgang, Maier, Robert M., Marchini, Jonathan, Martinsson, Lina, Mbarek, Hamdi, McCarroll, Steve, McGrath, Patrick, McGuffin, Peter, McInnis, Melvin G., McKay, James D., Medeiros, Helena, Medland, Sarah E., Mehta, Divya, Meng, Fan, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mirza, Saira Saeed, Mondimore, Francis M., Montgomery, Grant W., Morris, Derek W., Mostafavi, Sara, Mühleisen, Thomas W., Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nguyen, Hoang, Nievergelt, Caroline M., Nivard, Michel G., Nwulia, Evaristus A., Nyholt, Dale R., O'Donovan, Claire, O'Reilly, Paul F., Ori, Anil P.S., Oruc, Lilijana, Ösby, Urban, Oskarsson, Hogni, Painter, Jodie N., Parra, José Guzman, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Perry, Amy, Peterson, Roseann E., Pettersson, Erik, Peyrot, Wouter J., Pfennig, Andrea, Pistis, Giorgio, Purcell, Shaun M., Quiroz, Jorge A., Qvist, Per, Regeer, Eline J., Reif, Andreas, Reinbold, Céline S., Rice, John P., Riley, Brien P., Rivas, Fabio, Rivera, Margarita, Roussos, Panos, Ruderfer, Douglas M., Ryu, Euijung, Sánchez-Mora, Cristina, Schatzberg, Alan F., Scheftner, William A., Schoevers, Robert, Schork, Nicholas J., Schulte, Eva C., Shehktman, Tatyana, Shen, Ling, Shi, Jianxin, Shilling, Paul D., Shyn, Stanley I., Sigurdsson, Engilbert, Slaney, Claire, Smeland, Olav B., Smit, Johannes H., Smith, Daniel J., Sobell, Janet L., Spijker, Anne T., Steffens, Michael, Strauss, John S., Streit, Fabian, Strohmaier, Jana, Szelinger, Szabolcs, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Robert C., Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Uitterlinden, André G., Umbricht, Daniel, Vedder, Helmut, Viktorin, Alexander, Visscher, Peter M., Wang, Weiqing, Watson, Stanley J., Webb, Bradley T., Weickert, Cynthia Shannon, Weickert, Thomas W., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Xu, Wei, Yang, Jian, Young, Allan H., Zandi, Peter, Zhang, Peng, Zhang, Futao, Zollner, Sebastian, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Arolt, Volker, Backlund, Lena, Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Berrettini, Wade H., Biernacka, Joanna M., Blackwood, Douglas H.R., Boehnke, Michael, Boomsma, Dorret I., Corvin, Aiden, Craddock, Nicholas, Daly, Mark J., Dannlowski, Udo, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Etain, Bruno, Frye, Mark, Fullerton, Janice M., Gershon, Elliot S., de Geus, E.J.C., Gill, Michael, Goes, Fernando, Grabe, Hans J., Grigoroiu-Serbanescu, Maria, Hamilton, Steven P., Hauser, Joanna, Hayward, Caroline, Heath, Andrew C., Hougaard, David M., Hultman, Christina M., Jones, Ian, Jones, Lisa A., Kahn, René S., Kendler, Kenneth S., Kirov, George, Kloiber, Stefan, Landén, Mikael, Leboyer, Marion, Lewis, Glyn, Li, Qingqin S., Lissowska, Jolanta, Lucae, Susanne, Madden, Pamela A.F., Magnusson, Patrik K., Martin, Nicholas G., Mayoral, Fermin, McElroy, Susan L., McIntosh, Andrew M., McMahon, Francis J., Melle, Ingrid, Metspalu, Andres, Mitchell, Philip B., Morken, Gunnar, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Myers, Richard M., Neale, Benjamin M., Nimgaonkar, Vishwajit, Nordentoft, Merete, Nöthen, Markus M., O'Donovan, Michael C., Oedegaard, Ketil J., Owen, Michael J., Paciga, Sara A., Pato, Carlos, Pato, Michele T., Pedersen, Nancy L., Penninx, Brenda W.J. H., Perlis, Roy H., Porteous, David J., Posthuma, Danielle, Potash, James B., Preisig, Martin, Ramos-Quiroga, Josep Antoni, Ribasés, Marta, Rietschel, Marcella, Rouleau, Guy A., Schaefer, Catherine, Schalling, Martin, Schofield, Peter R., Schulze, Thomas G., Serretti, Alessandro, Smoller, Jordan W., Stefansson, Hreinn, Stefansson, Kari, Stordal, Eystein, Tiemeier, Henning, Turecki, Gustavo, Uher, Rudolf, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Andreassen, Ole A., Børglum, Anders D., Cichon, Sven, Edenberg, Howard J., Di Florio, Arianna, Kelsoe, John, Levinson, Douglas F., Lewis, Cathryn M., Nurnberger, John I., Ophoff, Roel A., Scott, Laura J., Sklar, Pamela, Sullivan, Patrick F., Wray, Naomi R., Coleman, Jonathan R.I., Gaspar, Héléna A., Bryois, Julien, and Breen, Gerome
Published: 2020
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15. Characterization of Single Gene Copy Number Variants in Schizophrenia

Author: Szatkiewicz, Jin P., Fromer, Menachem, Nonneman, Randal J., Ancalade, NaEshia, Johnson, Jessica S., Stahl, Eli A., Rees, Elliott, Bergen, Sarah E., Hultman, Christina M., Kirov, George, O’Donovan, Michael, Owen, Michael, Holmans, Peter, Sklar, Pamela, Sullivan, Patrick F., Purcell, Shaun M., Crowley, James J., and Ruderfer, Douglas M.
Published: 2020
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16. Genome-wide association analysis of composite sleep health scores in 413,904 individuals

Author: Goodman, Matthew O, primary, Faquih, Tariq, additional, Paz, Valentina, additional, Nagarajan, Pavithra, additional, Lane, Jacqueline M, additional, Spitzer, Brian, additional, Maher, Matthew, additional, Chung, Joon, additional, Cade, Brian E, additional, Purcell, Shaun M, additional, Zhu, Xiaofeng, additional, Noordam, Raymond, additional, Phillips, Andrew J. K., additional, Kyle, Simon D., additional, Spiegelhalder, Kai, additional, Weedon, Michael N, additional, Lawlor, Deborah A., additional, Rotter, Jerome I, additional, Taylor, Kent D, additional, Isasi, Carmen R, additional, Sofer, Tamar, additional, Dashti, Hassan S, additional, Rutter, Martin K, additional, Redline, Susan, additional, Saxena, Richa, additional, and Wang, Heming, additional
Published: 2024
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17. Mir137 Polygenic Risk for Schizophrenia and Ephrin-Regulated Pathway: Role in Lateral Ventricles and Corpus Callosum Volume

Author: Blokland, Gabriëlla Antonina Maria, primary, Maleki, Nasim, additional, Jovicich, Jorge, additional, Mesholam-Gately, Raquelle, additional, DeLisi, Lynn E., additional, Turner, Jessica A., additional, Shenton, Martha E., additional, Voineskos, Aristotle, additional, Kahn, Rene S., additional, Roffman, Joshua L., additional, Holt, Daphne J., additional, Ehrlich, Stefan, additional, Kikinis, Zora, additional, Dazzan, Paola, additional, Murray, Robin, additional, Lee, Jimmy, additional, Sim, Kang, additional, Lam, Max, additional, de Zwarte, Sonja M. C., additional, Walton, Esther, additional, Kelly, Sinead, additional, Picchioni, Marco M., additional, Bramon, Elvira, additional, Makris, Nikos, additional, David, Anthony S., additional, Mondelli, Valeria, additional, Reinders, Antje ATS, additional, Oykhman, Efim, additional, Morris, Derek W., additional, Gill, Michael, additional, Corvin, Aiden, additional, Cahn, Wiepke, additional, Ho, New Fei, additional, Liu, Jianjun, additional, Gollub, Randy L., additional, Manoach, Dara S., additional, Calhoun, Vince D., additional, Sponheim, Scott R., additional, Buka, Stephen, additional, Cherkerzian, Sara, additional, Thermenos, Heidi W., additional, Dickie, Erin W., additional, Ciufolini, Simone, additional, Reis Marques, Tiago, additional, Crossley, Nicolas A., additional, Purcell, Shaun M., additional, Smoller, Jordan W., additional, van Haren, Neeltje E.M., additional, Toulopoulou, Timothea, additional, Donohoe, Gary, additional, Goldstein, Jill M., additional, Keshavan, Matcheri S., additional, Petryshen, Tracey L., additional, and del Re, Elisabetta Claudia, additional
Published: 2024
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18. Analysis of protein-coding genetic variation in 60,706 humans.

Author: Lek, Monkol, Karczewski, Konrad J, Minikel, Eric V, Samocha, Kaitlin E, Banks, Eric, Fennell, Timothy, O'Donnell-Luria, Anne H, Ware, James S, Hill, Andrew J, Cummings, Beryl B, Tukiainen, Taru, Birnbaum, Daniel P, Kosmicki, Jack A, Duncan, Laramie E, Estrada, Karol, Zhao, Fengmei, Zou, James, Pierce-Hoffman, Emma, Berghout, Joanne, Cooper, David N, Deflaux, Nicole, DePristo, Mark, Do, Ron, Flannick, Jason, Fromer, Menachem, Gauthier, Laura, Goldstein, Jackie, Gupta, Namrata, Howrigan, Daniel, Kiezun, Adam, Kurki, Mitja I, Moonshine, Ami Levy, Natarajan, Pradeep, Orozco, Lorena, Peloso, Gina M, Poplin, Ryan, Rivas, Manuel A, Ruano-Rubio, Valentin, Rose, Samuel A, Ruderfer, Douglas M, Shakir, Khalid, Stenson, Peter D, Stevens, Christine, Thomas, Brett P, Tiao, Grace, Tusie-Luna, Maria T, Weisburd, Ben, Won, Hong-Hee, Yu, Dongmei, Altshuler, David M, Ardissino, Diego, Boehnke, Michael, Danesh, John, Donnelly, Stacey, Elosua, Roberto, Florez, Jose C, Gabriel, Stacey B, Getz, Gad, Glatt, Stephen J, Hultman, Christina M, Kathiresan, Sekar, Laakso, Markku, McCarroll, Steven, McCarthy, Mark I, McGovern, Dermot, McPherson, Ruth, Neale, Benjamin M, Palotie, Aarno, Purcell, Shaun M, Saleheen, Danish, Scharf, Jeremiah M, Sklar, Pamela, Sullivan, Patrick F, Tuomilehto, Jaakko, Tsuang, Ming T, Watkins, Hugh C, Wilson, James G, Daly, Mark J, MacArthur, Daniel G, and Exome Aggregation Consortium
Subjects: Exome Aggregation Consortium, Humans, Rare Diseases, Proteome, Sample Size, DNA Mutational Analysis, Phenotype, Genetic Variation, Exome, Datasets as Topic, Clinical Research, Biotechnology, Human Genome, Genetics, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, General Science & Technology
Abstract: Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. Here we describe the aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of predicted protein-truncating variants, with 72% of these genes having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human 'knockout' variants in protein-coding genes.
Published: 2016

19. Polygenic overlap between schizophrenia risk and antipsychotic response: a genomic medicine approach

Author: Ruderfer, Douglas M, Charney, Alexander W, Readhead, Ben, Kidd, Brian A, Kähler, Anna K, Kenny, Paul J, Keiser, Michael J, Moran, Jennifer L, Hultman, Christina M, Scott, Stuart A, Sullivan, Patrick F, Purcell, Shaun M, Dudley, Joel T, and Sklar, Pamela
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Mental Health, Genetics, Prevention, Biotechnology, Serious Mental Illness, Clinical Research, Brain Disorders, Human Genome, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Aetiology, Development of treatments and therapeutic interventions, Mental health, Good Health and Well Being, Antipsychotic Agents, Case-Control Studies, Clozapine, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Multifactorial Inheritance, Registries, Sweden, Treatment Outcome, Clinical Sciences, Public Health and Health Services, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract: BackgroundTherapeutic treatments for schizophrenia do not alleviate symptoms for all patients and efficacy is limited by common, often severe, side-effects. Genetic studies of disease can identify novel drug targets, and drugs for which the mechanism has direct genetic support have increased likelihood of clinical success. Large-scale genetic studies of schizophrenia have increased the number of genes and gene sets associated with risk. We aimed to examine the overlap between schizophrenia risk loci and gene targets of a comprehensive set of medications to potentially inform and improve treatment of schizophrenia.MethodsWe defined schizophrenia risk loci as genomic regions reaching genome-wide significance in the latest Psychiatric Genomics Consortium schizophrenia genome-wide association study (GWAS) of 36 989 cases and 113 075 controls and loss of function variants observed only once among 5079 individuals in an exome-sequencing study of 2536 schizophrenia cases and 2543 controls (Swedish Schizophrenia Study). Using two large and orthogonally created databases, we collated drug targets into 167 gene sets targeted by pharmacologically similar drugs and examined enrichment of schizophrenia risk loci in these sets. We further linked the exome-sequenced data with a national drug registry (the Swedish Prescribed Drug Register) to assess the contribution of rare variants to treatment response, using clozapine prescription as a proxy for treatment resistance.FindingsWe combined results from testing rare and common variation and, after correction for multiple testing, two gene sets were associated with schizophrenia risk: agents against amoebiasis and other protozoal diseases (106 genes, p=0·00046, pcorrected =0·024) and antipsychotics (347 genes, p=0·00078, pcorrected=0·046). Further analysis pointed to antipsychotics as having independent enrichment after removing genes that overlapped these two target sets. We noted significant enrichment both in known targets of antipsychotics (70 genes, p=0·0078) and novel predicted targets (277 genes, p=0·019). Patients with treatment-resistant schizophrenia had an excess of rare disruptive variants in gene targets of antipsychotics (347 genes, p=0·0067) and in genes with evidence for a role in antipsychotic efficacy (91 genes, p=0·0029).InterpretationOur results support genetic overlap between schizophrenia pathogenesis and antipsychotic mechanism of action. This finding is consistent with treatment efficacy being polygenic and suggests that single-target therapeutics might be insufficient. We provide evidence of a role for rare functional variants in antipsychotic treatment response, pointing to a subset of patients where their genetic information could inform treatment. Finally, we present a novel framework for identifying treatments from genetic data and improving our understanding of therapeutic mechanism.FundingUS National Institutes of Health.
Published: 2016

20. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders

Author: Singh, Tarjinder, Kurki, Mitja I, Curtis, David, Purcell, Shaun M, Crooks, Lucy, McRae, Jeremy, Suvisaari, Jaana, Chheda, Himanshu, Blackwood, Douglas, Breen, Gerome, Pietiläinen, Olli, Gerety, Sebastian S, Ayub, Muhammad, Blyth, Moira, Cole, Trevor, Collier, David, Coomber, Eve L, Craddock, Nick, Daly, Mark J, Danesh, John, DiForti, Marta, Foster, Alison, Freimer, Nelson B, Geschwind, Daniel, Johnstone, Mandy, Joss, Shelagh, Kirov, Georg, Körkkö, Jarmo, Kuismin, Outi, Holmans, Peter, Hultman, Christina M, Iyegbe, Conrad, Lönnqvist, Jouko, Männikkö, Minna, McCarroll, Steve A, McGuffin, Peter, McIntosh, Andrew M, McQuillin, Andrew, Moilanen, Jukka S, Moore, Carmel, Murray, Robin M, Newbury-Ecob, Ruth, Ouwehand, Willem, Paunio, Tiina, Prigmore, Elena, Rees, Elliott, Roberts, David, Sambrook, Jennifer, Sklar, Pamela, Clair, David St, Veijola, Juha, Walters, James TR, Williams, Hywel, Sullivan, Patrick F, Hurles, Matthew E, O'Donovan, Michael C, Palotie, Aarno, Owen, Michael J, and Barrett, Jeffrey C
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Genetics, Serious Mental Illness, Human Genome, Schizophrenia, Biotechnology, Brain Disorders, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Case-Control Studies, Cohort Studies, Female, Finland, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Histone-Lysine N-Methyltransferase, Humans, Male, Neurodevelopmental Disorders, Swedish Schizophrenia Study, INTERVAL Study, DDD Study, UK10 K Consortium, Neurosciences, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: By analyzing the whole-exome sequences of 4,264 schizophrenia cases, 9,343 controls and 1,077 trios, we identified a genome-wide significant association between rare loss-of-function (LoF) variants in SETD1A and risk for schizophrenia (P = 3.3 × 10(-9)). We found only two heterozygous LoF variants in 45,376 exomes from individuals without a neuropsychiatric diagnosis, indicating that SETD1A is substantially depleted of LoF variants in the general population. Seven of the ten individuals with schizophrenia carrying SETD1A LoF variants also had learning difficulties. We further identified four SETD1A LoF carriers among 4,281 children with severe developmental disorders and two more carriers in an independent sample of 5,720 Finnish exomes, both with notable neuropsychiatric phenotypes. Together, our observations indicate that LoF variants in SETD1A cause a range of neurodevelopmental disorders, including schizophrenia. Combining these data with previous common variant evidence, we suggest that epigenetic dysregulation, specifically in the histone H3K4 methylation pathway, is an important mechanism in the pathogenesis of schizophrenia.
Published: 2016

21. Causal Association Between Subtypes of Excessive Daytime Sleepiness and Risk of Cardiovascular Diseases

Author: Goodman, Matthew O., primary, Dashti, Hassan S., additional, Lane, Jacqueline M., additional, Windred, Daniel P., additional, Burns, Angus, additional, Jones, Samuel E., additional, Sofer, Tamar, additional, Purcell, Shaun M., additional, Zhu, Xiaofeng, additional, Ollila, Hanna M., additional, Kyle, Simon D., additional, Spiegelhalder, Kai, additional, Peker, Yuksel, additional, Huang, Tianyi, additional, Cain, Sean W., additional, Phillips, Andrew J. K., additional, Saxena, Richa, additional, Rutter, Martin K., additional, Redline, Susan, additional, and Wang, Heming, additional
Published: 2023
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22. Second-generation PLINK: rising to the challenge of larger and richer datasets

Author: Chang, Christopher C., Chow, Carson C., Tellier, Laurent C. A. M., Vattikuti, Shashaank, Purcell, Shaun M., and Lee, James J.
Subjects: Quantitative Biology - Genomics, Statistics - Computation, G.3, G.4, J.3
Abstract: PLINK 1 is a widely used open-source C/C++ toolset for genome-wide association studies (GWAS) and research in population genetics. However, the steady accumulation of data from imputation and whole-genome sequencing studies has exposed a strong need for even faster and more scalable implementations of key functions. In addition, GWAS and population-genetic data now frequently contain probabilistic calls, phase information, and/or multiallelic variants, none of which can be represented by PLINK 1's primary data format. To address these issues, we are developing a second-generation codebase for PLINK. The first major release from this codebase, PLINK 1.9, introduces extensive use of bit-level parallelism, O(sqrt(n))-time/constant-space Hardy-Weinberg equilibrium and Fisher's exact tests, and many other algorithmic improvements. In combination, these changes accelerate most operations by 1-4 orders of magnitude, and allow the program to handle datasets too large to fit in RAM. This will be followed by PLINK 2.0, which will introduce (a) a new data format capable of efficiently representing probabilities, phase, and multiallelic variants, and (b) extensions of many functions to account for the new types of information. The second-generation versions of PLINK will offer dramatic improvements in performance and compatibility. For the first time, users without access to high-end computing resources can perform several essential analyses of the feature-rich and very large genetic datasets coming into use., Comment: 2 figures, 1 additional file
Published: 2014
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23. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author: O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, 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, Bayes, Monica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas HR, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, Rene, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, and Fanous, Ayman
Subjects: Human Genome, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Depression, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Brain, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Mental Disorders, Signal Transduction, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.
Published: 2015

24. Publisher Correction: Macro and micro sleep architecture and cognitive performance in older adults

Author: Djonlagic, Ina, Mariani, Sara, Fitzpatrick, Annette L., Van Der Klei, Veerle M. G. T. H., Johnson, Dayna A., Wood, Alexis C., Seeman, Teresa, Nguyen, Ha T., Prerau, Michael J., Luchsinger, José A., Dzierzewski, Joseph M., Rapp, Stephen R., Tranah, Gregory J., Yaffe, Kristine, Burdick, Katherine E., Stone, Katie L., Redline, Susan, and Purcell, Shaun M.
Published: 2021
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25. Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Author: Gusev, Alexander, Lee, S Hong, Trynka, Gosia, Finucane, Hilary, Vilhjálmsson, Bjarni J, Xu, Han, Zang, Chongzhi, Ripke, Stephan, Bulik-Sullivan, Brendan, Stahl, Eli, Kähler, Anna K, Hultman, Christina M, Purcell, Shaun M, McCarroll, Steven A, Daly, Mark J, Pasaniuc, Bogdan, Sullivan, Patrick F, Neale, Benjamin M, Wray, Naomi R, Raychaudhuri, Soumya, Price, Alkes, Corvin, Aiden, Walters, James TR, Farh, Kai-How, Holmans, Peter A, Lee, Phil, Collier, David A, Huang, Hailiang, Pers, Tune H, Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A, Begemann, Martin, Belliveau, Richard A, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Børglum, Anders D, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Catts, Stanley V, Chambert, Kimberly D, Chan, Raymond CK, Chen, Ronald YL, Chen, Eric YH, Cheng, Wei, Cheung, Eric FC, Chong, Siow Ann, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Cormican, Paul, Craddock, Nick, Crowley, James J, Curtis, David, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Dudbridge, Frank, Durmishi, Naser, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Essioux, Laurent, Fanous, Ayman H, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freimer, Nelson B, Friedl, Marion, Friedman, Joseph I, Fromer, Menachem, Genovese, Giulio, and Georgieva, Lyudmila
Subjects: Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Prevention, Computer Simulation, Genetic Diseases, Inborn, Genetic Variation, Genome-Wide Association Study, Humans, Inheritance Patterns, Models, Genetic, Open Reading Frames, Regulatory Elements, Transcriptional, Schizophrenia Working Group of the Psychiatric Genomics Consortium, SWE-SCZ Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
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
Published: 2014

26. F95. GENETIC CORRELATES OF SLEEP SPINDLE ABNORMALITIES IN SCHIZOPHRENIA

Author: Wang, Jun, primary, Kozhemiako, Nataliia, additional, Jiang, Chenguang, additional, Guo, Zhenglin, additional, Chapman, Sinéad, additional, Li, Shen, additional, Shen, Lu, additional, Qin, Shengying, additional, Murphy, Michael, additional, Manoach, Dara, additional, Zhou, Zhenhe, additional, Hall, Meihua, additional, Pan, Jen Q, additional, Huang, Hailiang, additional, and Purcell, Shaun M, additional
Published: 2023
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27. Objectively regular sleep patterns and mortality in a prospective cohort: The Multi‐Ethnic Study of Atherosclerosis

Author: Chung, Joon, primary, Goodman, Matthew O., additional, Huang, Tianyi, additional, Castro‐Diehl, Cecilia, additional, Chen, Jarvis T., additional, Sofer, Tamar, additional, Bertisch, Suzanne M., additional, Purcell, Shaun M., additional, and Redline, Susan, additional
Published: 2023
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28. The Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) consortium: A collaborative cognitive and neuroimaging genetics project

Author: Blokland, Gabriëlla A.M., del Re, Elisabetta C., Mesholam-Gately, Raquelle I., Jovicich, Jorge, Trampush, Joey W., Keshavan, Matcheri S., DeLisi, Lynn E., Walters, James T.R., Turner, Jessica A., Malhotra, Anil K., Lencz, Todd, Shenton, Martha E., Voineskos, Aristotle N., Rujescu, Dan, Giegling, Ina, Kahn, René S., Roffman, Joshua L., Holt, Daphne J., Ehrlich, Stefan, Kikinis, Zora, Dazzan, Paola, Murray, Robin M., Di Forti, Marta, Lee, Jimmy, Sim, Kang, Lam, Max, Wolthusen, Rick P.F., de Zwarte, Sonja M.C., Walton, Esther, Cosgrove, Donna, Kelly, Sinead, Maleki, Nasim, Osiecki, Lisa, Picchioni, Marco M., Bramon, Elvira, Russo, Manuela, David, Anthony S., Mondelli, Valeria, Reinders, Antje A.T.S., Falcone, M. Aurora, Hartmann, Annette M., Konte, Bettina, Morris, Derek W., Gill, Michael, Corvin, Aiden P., Cahn, Wiepke, Ho, New Fei, Liu, Jian Jun, Keefe, Richard S.E., Gollub, Randy L., Manoach, Dara S., Calhoun, Vince D., Schulz, S. Charles, Sponheim, Scott R., Goff, Donald C., Buka, Stephen L., Cherkerzian, Sara, Thermenos, Heidi W., Kubicki, Marek, Nestor, Paul G., Dickie, Erin W., Vassos, Evangelos, Ciufolini, Simone, Reis Marques, Tiago, Crossley, Nicolas A., Purcell, Shaun M., Smoller, Jordan W., van Haren, Neeltje E.M., Toulopoulou, Timothea, Donohoe, Gary, Goldstein, Jill M., Seidman, Larry J., McCarley, Robert W., and Petryshen, Tracey L.
Published: 2018
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29. Rare Complete Knockouts in Humans: Population Distribution and Significant Role in Autism Spectrum Disorders

Author: 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, Project, NHLBI Exome Sequencing, 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
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Neurosciences, Psychology, Human Genome, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Pediatric, Genetics, Mental Health, Clinical Research, Autism, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Child Development Disorders, Pervasive, Child, Preschool, Chromosomes, Human, X, Demography, Female, Gene Deletion, Genetic Variation, Homozygote, Humans, Linkage Disequilibrium, Loss of Heterozygosity, Male, Risk Factors, NHLBI Exome Sequencing Project, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
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.
Published: 2013

30. Effects of a patient-derived de novo coding alteration of CACNA1I in mice connect a schizophrenia risk gene with sleep spindle deficits

Author: Ghoshal, Ayan, Uygun, David S., Yang, Lingling, McNally, James M., Lopez-Huerta, Violeta G., Arias-Garcia, Mario A., Baez-Nieto, David, Allen, Andrew, Fitzgerald, Megan, Choi, Soonwook, Zhang, Qiangge, Hope, Jen M., Yan, Karena, Mao, Xiaohong, Nicholson, Thomas B., Imaizumi, Kazuo, Fu, Zhanyan, Feng, Guoping, Brown, Ritchie E., Strecker, Robert E., Purcell, Shaun M., and Pan, Jen Q.
Published: 2020
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31. Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

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

Author: Pase, Matthew P., primary, Harrison, Stephanie, additional, Misialek, Jeffrey R., additional, Kline, Christopher E., additional, Cavuoto, Marina, additional, Baril, Andree-Ann, additional, Yiallourou, Stephanie, additional, Bisson, Alycia, additional, Himali, Dibya, additional, Leng, Yue, additional, Yang, Qiong, additional, Seshadri, Sudha, additional, Beiser, Alexa, additional, Gottesman, Rebecca F., additional, Redline, Susan, additional, Lopez, Oscar, additional, Lutsey, Pamela L., additional, Yaffe, Kristine, additional, Stone, Katie L., additional, Purcell, Shaun M., additional, and Himali, Jayandra J., additional
Published: 2023
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33. mTADA is a framework for identifying risk genes from de novo mutations in multiple traits

Author: Nguyen, Tan-Hoang, Dobbyn, Amanda, Brown, Ruth C., Riley, Brien P., Buxbaum, Joseph D., Pinto, Dalila, Purcell, Shaun M., Sullivan, Patrick F., He, Xin, and Stahl, Eli A.
Published: 2020
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34. Objectively regular sleep patterns and mortality in a prospective cohort: The Multi‐Ethnic Study of Atherosclerosis.

Author: Chung, Joon, Goodman, Matthew O., Huang, Tianyi, Castro‐Diehl, Cecilia, Chen, Jarvis T., Sofer, Tamar, Bertisch, Suzanne M., Purcell, Shaun M., and Redline, Susan
Subjects: DROWSINESS, SLEEP duration, PROPORTIONAL hazards models, SLEEP, COHORT analysis, K-means clustering
Abstract: Summary: Irregular sleep and non‐optimal sleep duration separately have been shown to be associated with increased disease and mortality risk. We used data from the prospective cohort Multi‐Ethnic Study of Atherosclerosis sleep study (2010–2013) to investigate: do aging adults whose sleep is objectively high in regularity in timing and duration, and of sufficient duration tend to have increased survival compared with those whose sleep is lower in regularity and duration, in a diverse US sample? At baseline, sleep was measured by 7‐day wrist actigraphy, concurrent with at‐home polysomnography and questionnaires. Objective metrics of sleep regularity and duration from actigraphy were used for statistical clustering using sparse k‐means clustering. Two sleep patterns were identified: "regular‐optimal" (average duration: 7.0 ± 1.0 hr obtained regularly) and "irregular‐insufficient" (duration: 5.8 ± 1.4 hr obtained with twice the irregularity). Using proportional hazard models with multivariate adjustment, we estimated all‐cause mortality hazard ratios. Among 1759 participants followed for a median of 7.0 years (Q1–Q3, 6.4–7.4 years), 176 deaths were recorded. The "regular‐optimal" group had a 39% lower mortality hazard than did the "irregular‐insufficient" sleep group (hazard ratio [95% confidence interval]: 0.61 [0.45, 0.83]) after adjusting for socio‐demographics, lifestyle, medical comorbidities and sleep disorders. In conclusion, a "regular‐optimal" sleep pattern was significantly associated with a lower hazard of all‐cause mortality. The regular‐optimal phenotype maps behaviourally to regular bed and wake times, suggesting sleep benefits of adherence to recommended healthy sleep practices, with further potential benefits for longevity. [ABSTRACT FROM AUTHOR]
Published: 2024
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35. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

Author: 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, Kiadeh, Farnush Hassan Farhadi, Finucane, Hilary K., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Giusti-Rodríguez, 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, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mill, Jonathan, 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., Pedersen, Carsten Bøcker, 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, Saeed Mirza, Saira, Saxena, Richa, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant B. C., 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, Van der Auwera, Sandra, van Hemert, Albert M., 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, eQTLGen, 23andMe, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. C. J., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, 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 F. A., 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 W. J. H., 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., Sullivan, Patrick F., and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Published: 2018
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36. AI-Driven sleep staging from actigraphy and heart rate

Author: Song, Tzu-An, primary, Chowdhury, Samadrita Roy, additional, Malekzadeh, Masoud, additional, Harrison, Stephanie, additional, Hoge, Terri Blackwell, additional, Redline, Susan, additional, Stone, Katie L., additional, Saxena, Richa, additional, Purcell, Shaun M., additional, and Dutta, Joyita, additional
Published: 2023
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37. Causal association between subtypes of excessive daytime sleepiness and risk of cardiovascular diseases

Author: Peker, Yüksel (ORCID 0000-0001-9067-6538 & YÖK ID 234103), Goodman, Matthew O.; Dashti, Hassan S.; Lane, Jacqueline M.; Windred, Daniel P.; Burns, Angus; Jones, Samuel E.; Sofer, Tamar; Purcell, Shaun M.; Zhu, Xiaofeng; Ollila, Hanna M.; Kyle, Simon D.; Spiegelhalder, Kai; Huang, Tianyi; Cain, Sean W.; Phillips, Andrew J. K.; Saxena, Richa; Rutter, Martin K.; Redline, Susan; Wang, Heming, School of Medicine, Peker, Yüksel (ORCID 0000-0001-9067-6538 & YÖK ID 234103), Goodman, Matthew O.; Dashti, Hassan S.; Lane, Jacqueline M.; Windred, Daniel P.; Burns, Angus; Jones, Samuel E.; Sofer, Tamar; Purcell, Shaun M.; Zhu, Xiaofeng; Ollila, Hanna M.; Kyle, Simon D.; Spiegelhalder, Kai; Huang, Tianyi; Cain, Sean W.; Phillips, Andrew J. K.; Saxena, Richa; Rutter, Martin K.; Redline, Susan; Wang, Heming, and School of Medicine
Abstract: Background: excessive daytime sleepiness (EDS), experienced in 10% to 20% of the population, has been associated with cardiovascular disease and death. However, the condition is heterogeneous and is prevalent in individuals having short and long sleep duration. We sought to clarify the relationship between sleep duration subtypes of EDS with cardiovascular outcomes, accounting for these subtypes. Methods and results: we defined 3 sleep duration subtypes of excessive daytime sleepiness: normal (6-9?hours), short (<6?hours), and long (>9?hours), and compared these with a nonsleepy, normal-sleep-duration reference group. We analyzed their associations with incident myocardial infarction (MI) and stroke using medical records of 355?901 UK Biobank participants and performed 2-sample Mendelian randomization for each outcome. Compared with healthy sleep, long-sleep EDS was associated with an 83% increased rate of MI (hazard ratio, 1.83 [95% CI, 1.21-2.77]) during 8.2-year median follow-up, adjusting for multiple health and sociodemographic factors. Mendelian randomization analysis provided supporting evidence of a causal role for a genetic long-sleep EDS subtype in MI (inverse-variance weighted ?=1.995, P=0.001). In contrast, we did not find evidence that other subtypes of EDS were associated with incident MI or any associations with stroke (P>0.05). Conclusions: our study suggests the previous evidence linking EDS with increased cardiovascular disease risk may be primarily driven by the effect of its long-sleep subtype on higher risk of MI. Underlying mechanisms remain to be investigated but may involve sleep irregularity and circadian disruption, suggesting a need for novel interventions in this population., This work was supported by the National Institute of Health grants R01HL153814 (to H.W.), National Heart, Lung, and Blood Institute R35HL135818 (to S.R.), and National Institute for Health and Care Research Manchester Biomedical Research Centre.
Published: 2023

38. Automated Processing of Big Data in Sleep Medicine

Author: Mariani, Sara, primary, Purcell, Shaun M., additional, and Redline, Susan, additional
Published: 2018
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39. Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes

Author: Wang, Heming, Lane, Jacqueline M., Jones, Samuel E., Dashti, Hassan S., Ollila, Hanna M., Wood, Andrew R., van Hees, Vincent T., Brumpton, Ben, Winsvold, Bendik S., Kantojärvi, Katri, Palviainen, Teemu, Cade, Brian E., Sofer, Tamar, Song, Yanwei, Patel, Krunal, Anderson, Simon G., Bechtold, David A., Bowden, Jack, Emsley, Richard, Kyle, Simon D., Little, Max A., Loudon, Andrew S., Scheer, Frank A. J. L., Purcell, Shaun M., Richmond, Rebecca C., Spiegelhalder, Kai, Tyrrell, Jessica, Zhu, Xiaofeng, Hublin, Christer, Kaprio, Jaakko A., Kristiansson, Kati, Sulkava, Sonja, Paunio, Tiina, Hveem, Kristian, Nielsen, Jonas B., Willer, Cristen J., Zwart, John-Anker, Strand, Linn B., Frayling, Timothy M., Ray, David, Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N., Redline, Susan, and Saxena, Richa
Published: 2019
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40. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Author: Dashti, Hassan S., Jones, Samuel E., Wood, Andrew R., Lane, Jacqueline M., van Hees, Vincent T., Wang, Heming, Rhodes, Jessica A., Song, Yanwei, Patel, Krunal, Anderson, Simon G., Beaumont, Robin N., Bechtold, David A., Bowden, Jack, Cade, Brian E., Garaulet, Marta, Kyle, Simon D., Little, Max A., Loudon, Andrew S., Luik, Annemarie I., Scheer, Frank A. J. L., Spiegelhalder, Kai, Tyrrell, Jessica, Gottlieb, Daniel J., Tiemeier, Henning, Ray, David W., Purcell, Shaun M., Frayling, Timothy M., Redline, Susan, Lawlor, Deborah A., Rutter, Martin K., Weedon, Michael N., and Saxena, Richa
Published: 2019
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41. Genetic Methodologies and Applications

Author: Purcell, Shaun M., additional
Published: 2017
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42. The relationship between sleep quality and neurocognition in bipolar disorder

Author: Russo, Manuela, Mahon, Katie, Shanahan, Megan, Ramjas, Elizabeth, Solon, Carly, Purcell, Shaun M., and Burdick, Katherine E.
Published: 2015
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43. Effect of predicted protein-truncating genetic variants on the human transcriptome

Author: The GTEx Consortium, The Geuvadis Consortium, Rivas, Manuel A., Pirinen, Matti, Conrad, Donald F., Lek, Monkol, Tsang, Emily K., Karczewski, Konrad J., Maller, Julian B., Kukurba, Kimberly R., DeLuca, David S., Fromer, Menachem, Ferreira, Pedro G., Smith, Kevin S., Zhang, Rui, Zhao, Fengmei, Banks, Eric, Poplin, Ryan, Ruderfer, Douglas M., Purcell, Shaun M., Tukiainen, Taru, Minikel, Eric V., Stenson, Peter D., Cooper, David N., Huang, Katharine H., Sullivan, Timothy J., Nedzel, Jared, Bustamante, Carlos D., Li, Jin Billy, Daly, Mark J., Guigo, Roderic, Donnelly, Peter, Ardlie, Kristin, Sammeth, Michael, Dermitzakis, Emmanouil T., McCarthy, Mark I., Montgomery, Stephen B., Lappalainen, Tuuli, and MacArthur, Daniel G.
Published: 2015

44. Sources of Variation in the Spectral Slope of the Sleep EEG

Author: Kozhemiako, Nataliia, primary, Mylonas, Dimitris, additional, Pan, Jen Q., additional, Prerau, Michael J., additional, Redline, Susan, additional, and Purcell, Shaun M., additional
Published: 2022
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45. Genetic modifiers and subtypes in schizophrenia: Investigations of age at onset, severity, sex and family history

Author: Bergen, Sarah E., O'Dushlaine, Colm T., Lee, Phil H., Fanous, Ayman H., Ruderfer, Douglas M., Ripke, Stephan, Sullivan, Patrick F., Smoller, Jordan W., Purcell, Shaun M., and Corvin, Aiden
Published: 2014
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46. A polygenic resilience score moderates the genetic risk for schizophrenia

Author: Hess, Jonathan L, Tylee, Daniel S, Mors, Ole, Duan, Jubao, Dudbridge, Frank, Duncanson, Audrey, Durmishi, Naser, Edkins, Sarah, Ehrenreich, Hannelore, Eichhammer, Peter, Eriksson, Johan, Escott-Price, Valentina, Esko, Tõnu, Nordentoft, Merete, Essioux, Laurent, Fanous, Ayman H, Farh, Kai-How, Farrell, Martilias S, Frank, Josef, Franke, Lude, Freedman, Robert, Freeman, Colin, Freimer, Nelson B, Friedl, Marion, Hougaard, David M, Friedman, Joseph I, Fromer, Menachem, Gejman, Pablo V, Genovese, Giulio, Georgieva, Lyudmila, Giannoulatou, Eleni, Giegling, Ina, Gill, Michael, Gillman, Matthew, Giusti-Rodríguez, Paola, Byberg-Grauholm, Jonas, Godard, Stephanie, Goldstein, Jacqueline I, Golimbet, Vera, Gopal, Srihari, Gratten, Jacob, Gray, Emma, Gurling, Hugh, Gwilliam, Rhian, de Haan, Lieuwe, Hall, Jeremy, Bækvad-Hansen, Marie, Hammer, Christian, Hammond, Naomi, Hamshere, Marian L, Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M, Hellenthal, Garrett, Henskens, Frans A, Herms, Stefan, Greenwood, Tiffany A, Hirschhorn, Joel N, Hoffmann, Per, Hofman, Andrea, Hollegaard, Mads V, Huang, Hailiang, Hultman, Christina M, Hunt, Sarah E, Ikeda, Masashi, Iwata, Nakao, Iyegbe, Conrad, Tsuang, Ming T, Jablensky, Assen V, Jankowski, Janusz, Jayakumar, Alagurevathi, Joa, Inge, Jönsson, Erik G, Julià, Antonio, Kähler, Anna K, Kahn, René S, Kalaydjieva, Luba, Karachanak-Yankova, Sena, Curtis, David, Karjalainen, Juha, Kavanagh, David, Keller, Matthew C, Kendler, Kenneth S, Kennedy, James L, Khrunin, Andrey, Kim, Yunjung, Kirov, George, Klovins, Janis, Knight, Jo, Steinberg, Stacy, Knowles, James A, Konte, Bettina, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kuzelova-Ptackova, Hana, Langford, Cordelia, Laurent, Claudine, Lawrie, Stephen, Lee, S Hong, Lee, Phil, Sigurdsson, Engilbert, Lee, Jimmy, Legge, Sophie E, Lencz, Todd, Lerer, Bernard, Levinson, Douglas F, Lewis, Cathryn M, Li, Tao, Li, Qingqin S, Li, Miaoxin, Liang, Kung-Yee, Mattheisen, Manuel, Stefánsson, Hreinn, Liddle, Jennifer, Lieberman, Jeffrey, Limborska, Svetlana, Lin, Kuang, Linszen, Don H, Liu, Jianjun, Lönnqvist, Jouko, Loughland, Carmel M, Lubinski, Jan, Macek, Milan, Stefánsson, Kári, Magnusson, Patrik K E, Maher, Brion S, Maier, Wolfgang, Malhotra, Anil K, Mallet, Jacques, Markus, Hugh S, Marsal, Sara, Mata, Ignacio, Mathew, Christopher G, Mattingsdal, Morten, Edenberg, Howard J, McCann, Owen T, McCarley, Robert W, McCarroll, Steven A, McCarthy, Mark I, McDonald, Colm, McIntosh, Andrew M, McQuillin, Andrew, Meier, Sandra, Meijer, Carin J, Melegh, Bela, Holmans, Peter, Melle, Ingrid, Mesholam-Gately, Raquelle I, Metspalu, Andres, Michie, Patricia T, Milani, Lili, Milanova, Vihra, Mokrab, Younes, Moran, Jennifer L, Morris, Derek W, Mowry, Bryan J, Faraone, Stephen V, Müller-Myhsok, Bertram, Murphy, Kieran C, Murray, Robin M, Myin-Germeys, Inez, Neale, Benjamin M, Nelis, Mari, Nenadic, Igor, Nertney, Deborah A, Nestadt, Gerald, Nicodemus, Kristin K, Glatt, Stephen J, Nikitina-Zake, Liene, Nisenbaum, Laura, Nordin, Annelie, Nöthen, Markus M, O'Callaghan, Eadbhard, O'Donovan, Michael C, O'Dushlaine, Colm, O'Neill, F Anthony, Oh, Sang-Yun, Olincy, Ann, Adolfsson, Rolf, Olsen, Line, Ophoff, Roel A, Van Os, Jim, Owen, Michael J, Palmer, Colin N A, Palotie, Aarno, Pantelis, Christos, Papadimitriou, George N, Papiol, Sergi, Parkhomenko, Elena, Agartz, Ingrid, Pato, Michele T, Pato, Carlos N, Paunio, Tiina, Pearson, Richard, Cairns, Murray J, DeLisi, Lynn E, Gershon, Elliot S, Kelly, Brian J, Lam, Max, Norgren, Nina, Agerbo, Esben, Paciga, Sara A, Tooney, Paul A, Wu, Jing Qin, Pejovic-Milovancevic, Milica, Perkins, Diana O, Pers, Tune H, Petryshen, Tracey L, Pietiläinen, Olli, Pimm, Jonathan, Pirinen, Matti, Albus, Margot, Plomin, Robert, Pocklington, Andrew J, Posthuma, Danielle, Potter, Simon C, Powell, John, Price, Alkes, Pulver, Ann E, Purcell, Shaun M, Quested, Digby, Rasmussen, Henrik B, Consortium, Schizophrenia Working Group of the Psychiatric Genomics, Alexander, Madeline, Rautanen, Anna, Ravindrarajah, Radhi, Reichenberg, Abraham, Reimers, Mark A, Richards, Alexander L, Ricketts, Michelle, Rietschel, Marcella, Riley, Brien P, Ripke, Stephan, Roffman, Joshua L, Amin, Farooq, Roussos, Panos, Ruderfer, Douglas M, Rujescu, Dan, Salomaa, Veikko, Sanders, Alan R, Sawcer, Stephen J, Schall, Ulrich, Schubert, Christian R, Schulze, Thomas G, Schwab, Sibylle G, Andreassen, Ole A, Scolnick, Edward M, Scott, Rodney J, Seidman, Larry J, Sham, Pak C, Shi, Jianxin, Silagadze, Teimuraz, Silverman, Jeremy M, Sim, Kang, Sklar, Pamela, Arranz, Maria J, Slominsky, Petr, Smoller, Jordan W, So, Hon-Cheong, Söderman, Erik, Spencer, Chris C A, Clair, David St, Stahl, Eli A, Stogmann, Elisabeth, Strange, Amy, Straub, Richard E, Bacanu, Silviu A, Strengman, Eric, Strohmaier, Jana, Stroup, T Scott, Su, Zhan, Subramaniam, Mythily, Sullivan, Patrick F, Suvisaari, Jaana, Svrakic, Dragan M, Szatkiewicz, Jin P, Tashakkori-Ghanbaria, Avazeh, Bakker, Steven, Thirumalai, Srinivas, Toncheva, Draga, Tosato, Sarah, Trembath, Richard C, Veijola, Juha, Visscher, Peter M, Viswanathan, Ananth C, Vukcevic, Damjan, Waddington, John, Waller, Matthew, Band, Gavin, Walsh, Dermot, Walshe, Muriel, Walters, James T R, Wang, Qiang, Wang, Dai, Webb, Bradley T, Weinberger, Daniel R, Weisbrod, Matthias, Weiser, Mark, Wendland, Jens R, Barroso, Ines, Weston, Paul, Whittaker, Pamela, Widaa, Sara, Wiersma, Durk, Wildenauer, Dieter B, Williams, Stephanie, Williams, Nigel M, Witt, Stephanie H, Wolen, Aaron R, Wong, Emily H M, Begemann, Martin, Wood, Nicholas W, Wormley, Brandon K, Wray, Naomi R, Xi, Hualin Simon, Zai, Clement C, Zheng, Xuebin, Zimprich, Fritz, Bellenguez, Céline, Research, Lundbeck Foundation Initiative for Integrative Psychiatric, Belliveau, Richard A, Bender, Stephan, Bene, Judit, Bergen, Sarah E, Bevilacqua, Elizabeth, Bigdeli, Tim B, Black, Donald W, Blackburn, Hannah, Blackwell, Jenefer M, Blackwood, Douglas H R, Børglum, Anders D, Bramon, Elvira, Brown, Matthew A, Bruggeman, Richard, Buccola, Nancy G, Buckner, Randy L, Bulik-Sullivan, Brendan, Bumpstead, Suzannah J, Buxbaum, Joseph D, Byerley, William, Cahn, Wiepke, Als, Thomas D, Cai, Guiqing, Campion, Dominique, Cantor, Rita M, Carr, Vaughan J, Carrera, Noa, Casas, Juan P, Catts, Stanley V, Chambert, Kimberley D, Chan, Ronald Y L, Chan, Raymond C K, Grove, Jakob, Chen, Eric Y H, Cheng, Wei, Cheung, Eric F C, Chong, Siow Ann, Cichon, Sven, Cloninger, C Robert, Cohen, David, Cohen, Nadine, Collier, David A, Cormican, Paul, Werge, Thomas, Corvin, Aiden, Craddock, Nick, Crespo-Facorro, Benedicto, Crowley, James J, Daly, Mark J, Darvasi, Ariel, Davidson, Michael, Davis, Kenneth L, Degenhardt, Franziska, Del Favero, Jurgen, Mortensen, Preben Bo, Deloukas, Panos, Demontis, Ditte, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Domenici, Enrico, Donnelly, Peter, Donohoe, Gary, Drapeau, Elodie, Dronov, Serge, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Hess, Jonathan L, Tylee, Daniel S, Mattheisen, Manuel, Borglum, Anders D, Glatt, Stephen J, Lee, Sand Hong, Schizophrenia Working Group of thePsychiatric Genomics Consortium, Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, and Myin-Germeys, Inez
Subjects: Multifactorial Inheritance, Schizophrenia/genetics, Genome-wide association study, Disease, Medical and Health Sciences, 0302 clinical medicine, Risk Factors, schizophrenia, genetics, risk, 2.1 Biological and endogenous factors, genetics, polygenic score, Aetiology, genome wide association study, risk, Genetics, Psychiatry, 0303 health sciences, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Genetic Predisposition to Disease/genetics, Single Nucleotide, Genomics, Biological Sciences, Serious Mental Illness, Polymorphism, Single Nucleotide/genetics, Penetrance, 3. Good health, Psychiatry and Mental health, Mental Health, Mendelian disease, Erfðarannsóknir, Life Sciences & Biomedicine, Single Nucleotide/genetics, Biochemistry & Molecular Biology, Schizophrenia (object-oriented programming), high risk, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Geðklofi, Humans, Genetic Predisposition to Disease, ddc:610, Allele, Polymorphism, Resilience (network), Molecular Biology, resilience, Multifactorial Inheritance/genetics, Alleles, 030304 developmental biology, Science & Technology, Prevention, Human Genome, Psychology and Cognitive Sciences, Neurosciences, Brain Disorders, Lundbeck Foundation Initiative for Integrative Psychiatric Research, schizophrenia, Good Health and Well Being, Schizophrenia, Neurosciences & Neurology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein), Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder., SJG is supported by grants from the U.S. National Institutes of Health (5R01MH101519, 5R01AG054002), the Sidney R. Baer, Jr. Foundation, and NARSAD: The Brain & Behavior Research Foundation. SVF is supported by the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement number 602805, the European Union’s Horizon 2020 research and innovation programme under grant agreement number 667302 and NIMH grants 5R01MH101519 and U01 MH109536-01. HJE is supported by grants from the U.S. National Institutes of Health (U10 AA008401; U01 MH109532). Statistical analyses were conducted on the Genetic Cluster Computer, which is financially supported by the Netherlands Scientific Organization (NOW; 480-05-003) along with a supplement from the Dutch Brain Foundation and VU University. The Danish iPSYCH (The Lundbeck Foundation Initiative for Integrative Psychiatric Research) and GEMS2 teams acknowledge funding from The Lundbeck Foundation (grant no R102-A9118 and R155-2014-1724), the Stanley Medical Research Institute, an Advanced Grant from the European Research Council (project no: 294838), the Danish Strategic Research Council and grants from Aarhus University to the iSEQ and CIRRAU centers. The Danish National Biobank resource at Statens Serum Institut was supported by the Novo Nordisk Foundation. Computational resources for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility were provided by the iSEQ center, Aarhus University, Denmark (grant to ADB).
Published: 2021

47. A transformer model for predicting cognitive impairment from sleep

Author: Song, Tzu-An, primary, Malekzadeh, Masoud, additional, Saxena, Richa, additional, Purcell, Shaun M., additional, and Dutta, Joyita, additional
Published: 2022
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48. Non-random mating, parent-of-origin, and maternal–fetal incompatibility effects in schizophrenia

Author: Kim, Yunjung, Ripke, Stephan, Kirov, George, Sklar, Pamela, Purcell, Shaun M., Owen, Michael J., O'Donovan, Michael C., and Sullivan, Patrick F.
Published: 2013
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49. Effects of a patient-derived de novo coding alteration of CACNA1I in mice connect a schizophrenia risk gene with sleep spindle deficits

Author: Ghoshal, Ayan, Uygun, David S., Yang, Lingling, McNally, James M., Lopez-Huerta, Violeta G., Arias-Garcia, Mario A., Baez-Nieto, David, Allen, Andrew, Fitzgerald, Megan, Choi, Soonwook, Zhang, Qiangge, Hope, Jen M., Yan, Karena, Mao, Xiaohong, Nicholson, Thomas B., Imaizumi, Kazuo, Fu, Zhanyan, Feng, Guoping, Brown, Ritchie E., Strecker, Robert E., Purcell, Shaun M., Pan, Jen Q., Ghoshal, Ayan, Uygun, David S., Yang, Lingling, McNally, James M., Lopez-Huerta, Violeta G., Arias-Garcia, Mario A., Baez-Nieto, David, Allen, Andrew, Fitzgerald, Megan, Choi, Soonwook, Zhang, Qiangge, Hope, Jen M., Yan, Karena, Mao, Xiaohong, Nicholson, Thomas B., Imaizumi, Kazuo, Fu, Zhanyan, Feng, Guoping, Brown, Ritchie E., Strecker, Robert E., Purcell, Shaun M., and Pan, Jen Q.
Abstract: © 2020, The Author(s). CACNA1I, a schizophrenia risk gene, encodes a subtype of voltage-gated T-type calcium channel CaV3.3. We previously reported that a patient-derived missense de novo mutation (R1346H) of CACNA1I impaired CaV3.3 channel function. Here, we generated CaV3.3-RH knock-in animals, along with mice lacking CaV3.3, to investigate the biological impact of R1346H (RH) variation. We found that RH mutation altered cellular excitability in the thalamic reticular nucleus (TRN), where CaV3.3 is abundantly expressed. Moreover, RH mutation produced marked deficits in sleep spindle occurrence and morphology throughout non-rapid eye movement (NREM) sleep, while CaV3.3 haploinsufficiency gave rise to largely normal spindles. Therefore, mice harboring the RH mutation provide a patient derived genetic model not only to dissect the spindle biology but also to evaluate the effects of pharmacological reagents in normalizing sleep spindle deficits. Importantly, our analyses highlighted the significance of characterizing individual spindles and strengthen the inferences we can make across species over sleep spindles. In conclusion, this study established a translational link between a genetic allele and spindle deficits during NREM observed in schizophrenia patients, representing a key step toward testing the hypothesis that normalizing spindles may be beneficial for schizophrenia patients.
Published: 2022

50. Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

Author: Kozhemiako, Nataliia, primary, Wang, Jun, primary, Jiang, Chenguang, primary, Wang, Lei A, additional, Gai, Guanchen, additional, Zou, Kai, additional, Wang, Zhe, additional, Yu, Xiaoman, additional, Zhou, Lin, additional, Li, Shen, additional, Guo, Zhenglin, additional, Law, Robert, additional, Coleman, James, additional, Mylonas, Dimitrios, additional, Shen, Lu, additional, Wang, Guoqiang, additional, Tan, Shuping, additional, Qin, Shengying, additional, Huang, Hailiang, additional, Murphy, Michael, additional, Stickgold, Robert, additional, Manoach, Dara, additional, Zhou, Zhenhe, additional, Zhu, Wei, additional, Hal, Mei-Hua, additional, Purcell, Shaun M, additional, and Pan, Jen Q, additional
Published: 2022
Full Text: View/download PDF

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