المؤلفون: Arranz, Maria J, Bakker, Steven, Bender, Stephan, Bramon, Elvira, Collier, David A, Crespo-Facorro, Benedicto, Hall, Jeremy, Iyegbe, Conrad, Jablensky, Assen V, Kahn, René S, Kalaydjieva, Luba, Lawrie, Stephen, Lewis, Cathryn M, Lin, Kuang, Linszen, Don H, Mata, Ignacio, McIntosh, Andrew M, Murray, Robin M, Ophoff, Roel A, Van Os, Jim, Powell, John, Rujescu, Dan, Walshe, Muriel, Weisbrod, Matthias, Wiersma, Durk, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris CA, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Giannoulatou, Eleni, Hellenthal, Garrett, Pearson, Richard, Pirinen, Matti, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Edkins, Sarah, Gillman, Matthew, Gray, Emma, Gwilliam, Rhian, Hammond, Naomi, Hunt, Sarah E, Jayakumar, Alagurevathi, Liddle, Jennifer, McCann, Owen T, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Tashakkori-Ghanbaria, Avazeh, Waller, Matthew, Weston, Paul, Whittaker, Pamela, Widaa, Sara, McCarthy, Mark I

المصدر: Nature. 582(7813)

مصطلحات موضوعية: Autoimmune Disease, Schizophrenia, Mental Health, Lupus, Genetics, Brain Disorders, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Adult, Alleles, Complement C3, Complement C4, Female, Genetic Predisposition to Disease, HLA Antigens, Haplotypes, Humans, Lupus Erythematosus, Systemic, Major Histocompatibility Complex, Male, Middle Aged, Sex Characteristics, Sjogren's Syndrome, Young Adult, Schizophrenia Working Group of the Psychiatric Genomics Consortium, General Science & Technology

الوصف: Many common illnesses, for reasons that have not been identified, differentially affect men and women. For instance, the autoimmune diseases systemic lupus erythematosus (SLE) and Sjögren's syndrome affect nine times more women than men1, whereas schizophrenia affects men with greater frequency and severity relative to women2. All three illnesses have their strongest common genetic associations in the major histocompatibility complex (MHC) locus, an association that in SLE and Sjögren's syndrome has long been thought to arise from alleles of the human leukocyte antigen (HLA) genes at that locus3-6. Here we show that variation of the complement component 4 (C4) genes C4A and C4B, which are also at the MHC locus and have been linked to increased risk for schizophrenia7, generates 7-fold variation in risk for SLE and 16-fold variation in risk for Sjögren's syndrome among individuals with common C4 genotypes, with C4A protecting more strongly than C4B in both illnesses. The same alleles that increase risk for schizophrenia greatly reduce risk for SLE and Sjögren's syndrome. In all three illnesses, C4 alleles act more strongly in men than in women: common combinations of C4A and C4B generated 14-fold variation in risk for SLE, 31-fold variation in risk for Sjögren's syndrome, and 1.7-fold variation in schizophrenia risk among men (versus 6-fold, 15-fold and 1.26-fold variation in risk among women, respectively). At a protein level, both C4 and its effector C3 were present at higher levels in cerebrospinal fluid and plasma8,9 in men than in women among adults aged between 20 and 50 years, corresponding to the ages of differential disease vulnerability. Sex differences in complement protein levels may help to explain the more potent effects of C4 alleles in men, women's greater risk of SLE and Sjögren's syndrome and men's greater vulnerability to schizophrenia. These results implicate the complement system as a source of sexual dimorphism in vulnerability to diverse illnesses.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6865z0pqTest

المؤلفون: Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden P, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris CA, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard D, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Tashakkori-Ghanbaria, Avazeh, Waller, Matthew J, Weston, Paul, Widaa, Sara, Whittaker, Pamela, McCarthy, Mark I

المصدر: Nature Genetics. 45(10)

مصطلحات موضوعية: Mental health, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Schizophrenia, Sweden, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Biological Sciences, Medical and Health Sciences, Developmental Biology

الوصف: Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5m70r4qgTest

المؤلفون: 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

المصدر: Molecular psychiatry 26, 800–815 (2021). doi:10.1038/s41380-019-0463-8

مصطلحات موضوعية: info:eu-repo/classification/ddc/610

جغرافية الموضوع: DE

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

العلاقة: info:eu-repo/semantics/altIdentifier/issn/1476-5578; info:eu-repo/semantics/altIdentifier/wos/WOS:000622346900008; info:eu-repo/semantics/altIdentifier/pmid/pmid:31492941; info:eu-repo/semantics/altIdentifier/hdl/2128/27386; info:eu-repo/semantics/altIdentifier/issn/1359-4184; https://juser.fz-juelich.de/record/865958Test; https://juser.fz-juelich.de/search?p=id:%22FZJ-2019-05224%22Test

الإتاحة: https://doi.org/10.1038/s41380-019-0463-8Test
https://juser.fz-juelich.de/record/865958Test
https://juser.fz-juelich.de/search?p=id:%22FZJ-2019-05224%22Test

المؤلفون: Ruderfer, Douglas M., Ripke, Stephan, McQuillin, Andrew, Boocock, James, Stahl, Eli A., Pavlides, Jennifer M. Whitehead, Mullins, Niamh, Charney, Alexander W., Ori, Anil P.S., Loohuis, Loes M. Olde, Domenici, Enrico, Di Florio, Arianna, Papiol, Sergi, Kalman, Janos L., Trubetskoy, Vassily, Adolfsson, Rolf, Agartz, Ingrid, Agerbo, Esben, Akil, Huda, Albani, Diego, Albus, Margot, Alda, Martin, Alexander, Madeline, Alliey-Rodriguez, Ney, Als, Thomas D., Amin, Farooq, Anjorin, Adebayo, Arranz, Maria J., Awasthi, Swapnil, Bacanu, Silviu A., Badner, Judith A., Baekvad-Hansen, Marie, Bakker, Steven, Band, Gavin, Barchas, Jack D., Barroso, Ines, Bass, Nicholas, Bauer, Michael, Baune, Bernhard T., Begemann, Martin, Bellenguez, Celine, Belliveau, Richard A., Bellivier, Frank, Bender, Stephan, Bene, Judit, Bergen, Sarah E., Berrettini, Wade H., Bevilacqua, Elizabeth, Biernacka, Joanna M., Bigdeli, Tim B., Black, Donald W., Blackburn, Hannah, Blackwell, Jenefer M., Blackwood, Douglas H.R., Pedersen, Carsten Bocker, Boehnke, Michael, Boks, Marco, Borglum, Anders D., Bramon, Elvira, Breen, Gerome, Brown, Matthew A., Bruggeman, Richard, Buccola, Nancy G., Buckner, Randy L., Budde, Monika, Bulik-Sullivan, Brendan, Bumpstead, Suzannah J., Bunney, William, Burmeister, Margit, Buxbaum, Joseph D., Bybjerg-Grauholm, Jonas, Byerley, William, Cahn, Wiepke, Cai, Guiqing, Cairns, Murray J., Campion, Dominique, Cantor, Rita M., Carr, Vaughan J., Carrera, Noa, Casas, Juan P., Casas, Miquel, Catts, Stanley V., Cervantes, Pablo, Chambert, Kimberley D., Chan, Raymond C.K., Chen, Eric Y.H., Chen, Ronald Y.L., Cheng, Wei, Cheung, Eric F.C., Chong, Siow Ann, Clarke, Toni-Kim, Cloninger, C. Robert, Cohen, David, Cohen, Nadine, Coleman, Jonathan R.I., Collier, David A., Cormican, Paul, Coryell, William, Craddock, Nicholas, Craig, David W., Crespo-Facorro, Benedicto, Crowley, James J., Cruceanu, Cristiana, Curtis, David, Czerski, Piotr M., Dale, Anders M., Daly, Mark J., Dannlowski, Udo, Darvasi, Ariel, Davidson, Michael, Davis, Kenneth L., de Leeuw, Christiaan A., Degenhardt, Franziska, Del Favero, Jurgen, DeLisi, Lynn E., Deloukas, Panos, Demontis, Ditte, DePaulo, J. Raymond, di Forti, Marta, Dikeos, Dimitris, Dinan, Timothy, Djurovic, Srdjan, Dobbyn, Amanda L., Donnelly, Peter, Donohoe, Gary, Drapeau, Elodie, Dronov, Serge, Duan, Jubao, Dudbridge, Frank, Duncanson, Audrey, Edenberg, Howard, Edkins, Sarah, Ehrenreich, Hannelore, Eichhammer, Peter, Elvsashagen, Torbjorn, Eriksson, Johan, Escott-Price, Valentina, Esko, Tonu, Essioux, Laurent, Etain, Bruno, Fan, Chun Chieh, Farh, Kai-How, Farrell, Martilias S., Flickinger, Matthew, Foroud, Tatiana M., Forty, Liz, Frank, Josef, Franke, Lude, Fraser, Christine, Freedman, Robert, Freeman, Colin, Freimer, Nelson B., Friedman, Joseph I., Fromer, Menachem, Frye, Mark A., Fullerton, Janice M., Gade, Katrin, Garnham, Julie, Gaspar, Helena A., Gejman, Pablo V., Genovese, Giulio, Georgieva, Lyudmila, Giambartolomei, Claudia, Giannoulatou, Eleni, Giegling, Ina, Gill, Michael, Gillman, Matthew, Pedersen, Marianne Giortz, Giusti-Rodriguez, Paola, Godard, Stephanie, Goes, Fernando, Goldstein, Jacqueline I., Gopal, Srihari, Gordon, Scott D., Gordon-Smith, Katherine, Gratten, Jacob, Gray, Emma, Green, Elaine K., Green, Melissa J., Greenwood, Tiffany A., Grigoroiu-Serbanescu, Maria, Grove, Jakob, Guan, Weihua, Gurling, Hugh, Parra, Jose Guzman, Gwilliam, Rhian, de Haan, Lieuwe, Hall, Jeremy, Hall, Mei-Hua, Hammer, Christian, Hammond, Naomi, Hamshere, Marian L., Hansen, Mark, Hansen, Thomas, Haroutunian, Vahram, Hartmann, Annette M., Hauser, Joanna, Hautzinger, Martin, Heilbronner, Urs, Hellenthal, Garrett, Henskens, Frans A., Herms, Stefan, Hipolito, Maria, Hirschhorn, Joel N., Hoffmann, Per, Hollegaard, Mads V., Hougaard, David M., Huang, Hailiang, Huckins, Laura, Hultman, Christina M., Hunt, Sarah E., Ikeda, Masashi, Iwata, Nakao, Iyegbe, Conrad, Jablensky, Assen V., Jamain, Stephane, Jankowski, Janusz, Jayakumar, Alagurevathi, Joa, Inge, Jones, Ian, Jones, Lisa A., Jonsson, Erik G., Julia, Antonio, Jureus, Anders, Kahler, Anna K., Kahn, Rene S., Kalaydjieva, Luba, Kandaswamy, Radhika, Karachanak-Yankova, Sena, Karjalainen, Juha, Karlsson, Robert, Kavanagh, David, Keller, Matthew C., Kelly, Brian J., Kelsoe, John, Kennedy, James L., Khrunin, Andrey, Kim, Yunjung, Kirov, George, Kittel-Schneider, Sarah, Klovins, Janis, Knight, Jo, Knott, Sarah V., Knowles, James A., Kogevinas, Manolis, Konte, Bettina, Kravariti, Eugenia, Kucinskas, Vaidutis, Kucinskiene, Zita Ausrele, Kupka, Ralph, Kuzelova-Ptackova, Hana, Landen, Mikael, Langford, Cordelia, Laurent, Claudine, Lawrence, Jacob, Lawrie, Stephen, Lawson, William B., Leber, Markus, Leboyer, Marion, Lee, Phil H., Keong, Jimmy Lee Chee, Legge, Sophie E., Lencz, Todd, Lerer, Bernard, Levinson, Douglas F., Levy, Shawn E., Lewis, Cathryn M., Li, Jun Z., Li, Miaoxin, Li, Qingqin S., Li, Tao, Liang, Kung-Yee, Liddle, Jennifer, Lieberman, Jeffrey, Limborska, Svetlana, Lin, Kuang, Linszen, Don H., Lissowska, Jolanta, Liu, Chunyu, Liu, Jianjun, Lonnqvist, Jouko, Loughland, Carmel M., Lubinski, Jan, Lucae, Susanne, Macek, Milan, MacIntyre, Donald J., Magnusson, Patrik K.E., Maher, Brion S., Mahon, Pamela B., Maier, Wolfgang, Malhotra, Anil K., Mallet, Jacques, Malt, Ulrik F., Markus, Hugh S., Marsal, Sara, Martin, Nicholas G., Mata, Ignacio, Mathew, Christopher G., Mattheisen, Manuel, Mattingsdal, Morten, Mayoral, Fermin, McCann, Owen T., McCarley, Robert W., McCarroll, Steven A., McCarthy, Mark I., McDonald, Colm, McElroy, Susan L., McGuffin, Peter, McInnis, Melvin G., McIntosh, Andrew M., McKay, James D., McMahon, Francis J., Medeiros, Helena, Medland, Sarah E., Meier, Sandra, Meijer, Carin J., Melegh, Bela, Melle, Ingrid, Meng, Fan, Mesholam-Gately, Raquelle I., Metspalu, Andres, Michie, Patricia T., Milani, Lili, Milanova, Vihra, Mitchell, Philip B., Mokrab, Younes, Montgomery, Grant W., Moran, Jennifer L., Morken, Gunnar, Morris, Derek W., Mors, Ole, Mortensen, Preben B., Mowry, Bryan J., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Murphy, Kieran C., Murray, Robin M., Myers, Richard M., Myin-Germeys, Inez, Neale, Benjamin M., Nelis, Mari, Nenadic, Igor, Nertney, Deborah A., Nestadt, Gerald, Nicodemus, Kristin K., Nievergelt, Caroline M., Nikitina-Zake, Liene, Nimgaonkar, Vishwajit, Nisenbaum, Laura, Nordentoft, Merete, Nordin, Annelie, Nöthen, Markus M., Nwulia, Evaristus A., O'Callaghan, Eadbhard, O'Donovan, Claire, O'Dushlaine, Colm, O'Neill, F. Anthony, Oedegaard, Ketil J., Oh, Sang-Yun, Olincy, Ann, Olsen, Line, Oruc, Lilijana, Van Os, Jim, Owen, Michael J., Paciga, Sara A., Palmer, Colin N.A., Palotie, Aarno, Pantelis, Christos, Papadimitriou, George N., Parkhomenko, Elena, Pato, Carlos, Pato, Michele T., Paunio, Tiina, Pearson, Richard, Perkins, Diana O., Perlis, Roy H., Perry, Amy, Pers, Tune H., Petryshen, Tracey L., Pfennig, Andrea, Picchioni, Marco, Pietilainen, Olli, Pimm, Jonathan, Pirinen, Matti, Plomin, Robert, Pocklington, Andrew J., Posthuma, Danielle, Potash, James B., Potter, Simon C., Powell, John, Price, Alkes, Pulver, Ann E., Purcell, Shaun M., Quested, Digby, Ramos-Quiroga, Josep Antoni, Rasmussen, Henrik B., Rautanen, Anna, Ravindrarajah, Radhi, Regeer, Eline J., Reichenberg, Abraham, Reif, Andreas, Reimers, Mark A., Ribases, Marta, Rice, John P., Richards, Alexander L., Ricketts, Michelle, Riley, Brien P., Rivas, Fabio, Rivera, Margarita, Roffman, Joshua L., Rouleau, Guy A., Roussos, Panos, Rujescu, Dan, Salomaa, Veikko, Sanchez-Mora, Cristina, Sanders, Alan R., Sawcer, Stephen J., Schall, Ulrich, Schatzberg, Alan F., Scheftner, William A., Schofield, Peter R., Schork, Nicholas J., Schwab, Sibylle G., Scolnick, Edward M., Scott, Laura J., Scott, Rodney J., Seidman, Larry J., Serretti, Alessandro, Sham, Pak C., Weickert, Cynthia Shannon, Shehktman, Tatyana, Shi, Jianxin, Shilling, Paul D., Sigurdsson, Engilbert, Silverman, Jeremy M., Sim, Kang, Slaney, Claire, Slominsky, Petr, Smeland, Olav B., Smoller, Jordan W., So, Hon-Cheong, Sobell, Janet L., Soderman, Erik, Hansen, Christine Soholm, Spencer, Chris C.A., Spijker, Anne T., St Clair, David, Stefansson, Hreinn, Stefansson, Kari, Steinberg, Stacy, Stogmann, Elisabeth, Stordal, Eystein, Strange, Amy, Straub, Richard E., Strauss, John S., Streit, Fabian, Strengman, Eric, Strohmaier, Jana, Stroup, T. Scott, Su, Zhan, Subramaniam, Mythily, Suvisaari, Jaana, Svrakic, Dragan M., Szatkiewicz, Jin P., Szelinger, Szabolcs, Tashakkori-Ghanbaria, Avazeh, Thirumalai, Srinivas, Thompson, Robert C., Thorgeirsson, Thorgeir E., Toncheva, Draga, Tooney, Paul A., Tosato, Sarah, Toulopoulou, Timothea, Trembath, Richard C., Treutlein, Jens, Turecki, Gustavo, Vaaler, Arne E., Vedder, Helmut, Vieta, Eduard, Vincent, John, Visscher, Peter M., Viswanathan, Ananth C., Vukcevic, Damjan, Waddington, John, Waller, Matthew, Walsh, Dermot, Walshe, Muriel, Walters, James T.R., Wang, Dai, Wang, Qiang, Wang, Weiqing, Wang, Yunpeng, Watson, Stanley J., Webb, Bradley T., Weickert, Thomas W., Weinberger, Daniel R., Weisbrod, Matthias, Weiser, Mark, Werge, Thomas, Weston, Paul, Whittaker, Pamela, Widaa, Sara, Wiersma, Durk, Wildenauer, Dieter B., Williams, Nigel M., Williams, Stephanie, Witt, Stephanie H., Wolen, Aaron R., Wong, Emily H.M., Wood, Nicholas W., Wormley, Brandon K., Wu, Jing Qin, Xi, Simon, Xu, Wei, Young, Allan H., Zai, Clement C., Zandi, Peter, Zhang, Peng, Zheng, Xuebin, Zimprich, Fritz, Zollner, Sebastian, Corvin, Aiden, Fanous, Ayman H., Cichon, Sven, Rietschel, Marcella, Gershon, Elliot S., Schulze, Thomas G., Cuellar-Barboza, Alfredo B., Forstner, Andreas J., Holmans, Peter A., Nurnberger, John I., Andreassen, Ole A., Lee, S. Hong, O'Donovan, Michael, Sullivan, Patrick F., Ophoff, Roel A., Wray, Naomi, Sklar, Pamela, Kendler, Kenneth S.

الوصف: Schizophrenia and bipolar disorder are two distinct diagnoses that share symptomology. Understanding the genetic factors contributing to the shared and disorder-specific symptoms will be crucial for improving diagnosis and treatment. In genetic data consisting of 53,555 cases (20,129 bipolar disorder [BD], 33,426 schizophrenia [SCZ]) and 54,065 controls, we identified 114 genome-wide significant loci implicating synaptic and neuronal pathways shared between disorders. Comparing SCZ to BD (23,585 SCZ, 15,270 BD) identified four genomic regions including one with disorder-independent causal variants and potassium ion response genes as contributing to differences in biology between the disorders. Polygenic risk score (PRS) analyses identified several significant correlations within case-only phenotypes including SCZ PRS with psychotic features and age of onset in BD. For the first time, we discover specific loci that distinguish between BD and SCZ and identify polygenic components underlying multiple symptom dimensions. These results point to the utility of genetics to inform symptomology and potential treatment.

وصف الملف: application/pdf

العلاقة: https://orca.cardiff.ac.uk/id/eprint/112551/1/BDSCZ2-final.pdfTest; Ruderfer, Douglas M., Ripke, Stephan, McQuillin, Andrew, Boocock, James, Stahl, Eli A., Pavlides, Jennifer M. Whitehead, Mullins, Niamh, Charney, Alexander W., Ori, Anil P.S., Loohuis, Loes M. 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الإتاحة: https://doi.org/10.1016/j.cell.2018.05.046Test
https://orca.cardiff.ac.uk/id/eprint/112551Test/
https://orca.cardiff.ac.uk/id/eprint/112551/1/BDSCZ2-final.pdfTest

المؤلفون: Jansen, Iris E., Ye, Hui, Heetveld, Sasja, Lechler, Marie C., Michels, Helen, Seinstra, Renée I., Lubbe, Steven J., Drouet, Valérie, Lesage, Suzanne, Majounie, Elisa, Gibbs, J. Raphael, Nalls, Mike A., Ryten, Mina, Botia, Juan A., Vandrovcova, Jana, Simon-Sanchez, Javier, Castillo-Lizardo, Melissa, Rizzu, Patrizia, Blauwendraat, Cornelis, Chouhan, Amit K., Li, Yarong, Yogi, Puja, Amin, Najaf, van Duijn, Cornelia M., Morris, Huw R., Brice, Alexis, Singleton, Andrew B., David, Della C., Nollen, Ellen A., Jain, Shushant, Shulman, Joshua M., Heutink, Peter, Hernandez, Dena G., Arepalli, Sampath, Brooks, Janet, Price, Ryan, Nicolas, Aude, Chong, Sean, Cookson, Mark R., Dillman, Allissa, Moore, Matthew, Traynor, Bryan J., Plagnol, Vincent, Nicholas W Wood, W Wood, Sheerin, Una Marie, Jose M Bras, M Bras, Charlesworth, Gavin, Gardner, Michelle, Guerreiro, Rita, Trabzuni, Daniah, Hardy, John, Sharma, Manu, Saad, Mohamad, Javier Simón-Sánchez, Simón-Sánchez, Schulte, Claudia, Corvol, Jean Christophe, Dürr, Alexandra, Vidailhet, Marie, Sveinbjörnsdóttir, Sigurlaug, Barker, Roger, Caroline H Williams-Gray, H Williams-Gray, Ben-Shlomo, Yoav, Berendse, Henk W., van Dijk, Karin D., Berg, Daniela, Brockmann, Kathrin, Wurster, Isabel, Mätzler, Walter, Gasser, Thomas, Martinez, Maria, de Bie, Rob M A, Biffi, Alessandro, Velseboer, Daan, Bloem, Bas, Post, Bart, Wickremaratchi, Mirdhu, van de Warrenburg, Bart, Bochdanovits, Zoltan, Bonin, Michael, Pétursson, Hjörvar, Riess, Olaf, Burn, David J., Lubbe, Steven, Cooper, J. Mark, McNeill, Alisdair, Schapira, Anthony, Lungu, Codrin, Chen, Honglei, Dong, Jing, Chinnery, Patrick F., Hudson, Gavin, Clarke, Carl E., Moorby, Catriona, Counsell, Carl, Damier, Philippe, Dartigues, Jean François, Deloukas, Panos, Edkins, Sarah, Hunt, Sarah E., Tashakkori-Ghanbaria, Avazeh, Deuschl, Günther, Lorenz, Delia, Dexter, David T., Durif, Frank, Evans, Jonathan R., Langford, Cordelia, Foltynie, Thomas, Goate, Alison, Harris, Clare, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Illig, Thomas, Jónsson, Pálmi V., Lambert, Jean Charles, O'Sullivan, Sean S., Revesz, Tamas, Shaw, Karen, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Escott-Price, Valentina, Pearson, Justin, Williams, Nigel, Mudanohwo, Ese, Perlmutter, Joel S., Pollak, Pierre, Rivadeneira, Fernando, Uitterlinden, André G., Sawcer, Stephen, Scheffer, Hans, Shoulson, Ira, Shulman, Joshua, Smith, Colin, Walker, Robert, Spencer, Chris C A, Strange, Amy, Stefánsson, Hreinn, Bettella, Francesco, Stefánsson, Kári, Stockton, Joanna D., Talbot, Kevin, Tanner, Carlie M., Tison, François, Winder-Rhodes, Sophie, Bhatia, Kailash

المصدر: Jansen , I E , Ye , H , Heetveld , S , Lechler , M C , Michels , H , Seinstra , R I , Lubbe , S J , Drouet , V , Lesage , S , Majounie , E , Gibbs , J R , Nalls , M A , Ryten , M , Botia , J A , Vandrovcova , J , Simon-Sanchez , J , Castillo-Lizardo , M , Rizzu , P , Blauwendraat , C , Chouhan , A K , Li , Y , Yogi , P , Amin , N ....

مصطلحات موضوعية: Animal model, Functional screening, Genomics, Loss-of-function, Mitochondria, Parkin, Parkinson's disease, Rare variants, Whole-exome sequencing, α-synuclein

الوصف: Background: Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach has not been deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES in 1148 unrelated cases and 503 control participants. Candidate genes were subsequently validated for functions relevant to PD based on parallel RNA-interference (RNAi) screens in human cell culture and Drosophila and C. elegans models. Results: Assuming autosomal recessive inheritance, we identify 27 genes that have homozygous or compound heterozygous loss-of-function variants in PD cases. Definitive replication and confirmation of these findings were hindered by potential heterogeneity and by the rarity of the implicated alleles. We therefore looked for potential genetic interactions with established PD mechanisms. Following RNAi-mediated knockdown, 15 of the genes modulated mitochondrial dynamics in human neuronal cultures and four candidates enhanced α-synuclein-induced neurodegeneration in Drosophila. Based on complementary analyses in independent human datasets, five functionally validated genes-GPATCH2L, UHRF1BP1L, PTPRH, ARSB, and VPS13C-also showed evidence consistent with genetic replication. Conclusions: By integrating human genetic and functional evidence, we identify several PD susceptibility gene candidates for further investigation. Our approach highlights a powerful experimental strategy with broad applicability for future studies of disorders with complex genetic etiologies.

وصف الملف: application/pdf

العلاقة: https://research-information.bris.ac.uk/en/publications/79108d1e-1e5e-4dee-8591-ba8caf5ddfc7Test

الإتاحة: https://doi.org/10.1186/s13059-017-1147-9Test
https://hdl.handle.net/1983/79108d1e-1e5e-4dee-8591-ba8caf5ddfc7Test
https://research-information.bris.ac.uk/en/publications/79108d1e-1e5e-4dee-8591-ba8caf5ddfc7Test
https://research-information.bris.ac.uk/ws/files/129753975/Full_text_PDF_final_published_version_.pdfTest

المؤلفون: Davis, Oliver S. P., Band, Gavin, Pirinen, Matti, Haworth, Claire M. A., Meaburn, Emma L., Kovas, Yulia, Harlaar, Nicole, Docherty, Sophia J., Hanscombe, Ken B., Trzaskowski, Maciej, Curtis, Charles J. C., Strange, Amy, Freeman, Colin, Bellenguez, Céline, Su, Zhan, Pearson, Richard, Vukcevic, Damjan, Langford, Cordelia, Deloukas, Panos, Hunt, Sarah, Gray, Emma, Dronov, Serge, Potter, Simon C., Tashakkori-Ghanbaria, Avazeh, Edkins, Sarah, Bumpstead, Suzannah J., Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz A Z, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Barroso, Ines, Peltonen, Leena, Dale, Philip S., Petrill, Stephen A., Schalkwyk, Leonard S., Craig, Ian W, Lewis, Cathryn M., Price, Thomas S., Donnelly, Peter

المصدر: Davis , O S P , Band , G , Pirinen , M , Haworth , C M A , Meaburn , E L , Kovas , Y , Harlaar , N , Docherty , S J , Hanscombe , K B , Trzaskowski , M , Curtis , C J C , Strange , A , Freeman , C , Bellenguez , C , Su , Z , Pearson , R , Vukcevic , D , Langford , C , Deloukas , P , Hunt , S , Gray , E , Dronov , S , Potter , ....

الوصف: Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

وصف الملف: application/pdf

العلاقة: https://discovery.dundee.ac.uk/en/publications/8990f64f-3f1e-44b2-93e4-a6a920ebc89eTest

الإتاحة: https://doi.org/10.1038/ncomms5204Test
https://discovery.dundee.ac.uk/en/publications/8990f64f-3f1e-44b2-93e4-a6a920ebc89eTest
https://discovery.dundee.ac.uk/ws/files/9087272/ncomms5204.pdfTest

المؤلفون: Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Kähler, Anna K, Akterin, Susanne, Bergen, Sarah E, Collins, Ann L, Crowley, James J, Fromer, Menachem, Kim, Yunjung, Bender, Stephan, Bramon, Elvira, Collier, David, Crespo-Facorro, Benedicto, Hall, Jeremy, Iyegbe, Conrad, McIntosh, Andrew, Murray, Robin M, Lee, Sang Hong, Ophoff, Roel A, Scolnick, Edward, Powell, John, Rujescu, Dan, Van Os, Jim, Walshe, Muriel, Weisbrod, Matthias, Wiersma, Durk, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Magnusson, Patrik K E, Purcell, Shaun, Brown, Matthew A, Casas, Juan P, Corvin, Aiden P, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin N A, McCarroll, Steven A, Sanchez, Nick, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris C A, Band, Gavin, Bellenguez, Céline, Sklar, Pamela, Freeman, Colin, Stahl, Eli A, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard D, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Hultman, Christina M, Langford, Cordelia, Hunt, Sarah E, Williams, Stephanie, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Sullivan, Patrick F, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Wray, Naomi R, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Tashakkori-Ghanbaria, Avazeh, Waller, Matthew J, Borglum, Anders D, Weston, Paul, Widaa, Sara, Whittaker, Pamela, Xia, Kai, Bulik-Sullivan, Brendan K, McCarthy, Mark I, O'Donovan, Michael C, Bettella, Francesco, Stefansson, Kari, Cormican, Paul, Craddock, Nick, Jablensky, Assen, de Leeuw, Christiaan, Durmishi, Naser, Gill, Michael, Golimbet, Vera, Hamshere, Marian L, Holmans, Peter, Hougaard, David M, Kendler, Kenneth S, Lin, Kuang, Morris, Derek W, Kahn, Rene S, Mors, Ole, Mortensen, Preben B, Neale, Benjamin M, O'Neill, Francis A, Owen, Michael J, Milovancevic, Milica Pejovic, Posthuma, Danielle, Richards, Alexander L, Riley, Brien P, Kalaydjieva, Luba, Ruderfer, Douglas, Sigurdsson, Engilbert, Silagadze, Teimuraz, Smit, August B, Stefansson, Hreinn, Steinberg, Stacy, Suvisaari, Jaana, Tosato, Sarah, Verhage, Matthijs, Lawrie, Stephen, Walters, James T, Levinson, Douglas F, Gejman, Pablo V, Laurent, Claudine, Mowry, Bryan J, Pulver, Ann E, Lewis, Cathryn M, Schwab, Sibylle G, Wildenauer, Dieter B, Dudbridge, Frank, Shi, Jianxin, Albus, Margot, Alexander, Madeline, Campion, Dominique, Cohen, David, Dikeos, Dimitris, Duan, Jubao, Eichhammer, Peter, Godard, Stephanie, Hansen, Mark, Lerer, F Bernard, Liang, Kung-Yee, Maier, Wolfgang, Mallet, Jacques, Nertney, Deborah A, Nestadt, Gerald, Linszen, Don H, Norton, Nadine, Papadimitriou, George N, Ribble, Robert, Sanders, Alan R, Silverman, Jeremy M, Walsh, Dermot, Williams, Nigel M, Wormley, Brandon, Arranz, Maria J, Mata, Ignacio, Bakker, Steven

المساهمون: Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA deCODE Genet, Reykjavik, Iceland Aarhus Univ Hosp, Risskov, Denmark Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia Statens Serum Inst, DK-2300 Copenhagen, Denmark Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Kings Coll London, Inst Psychiat, London, England Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, DenmarkQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Belgrade, Fac Med, Belgrade, Serbia Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands Kings Coll London, Dept Neurosci, London, England Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA Univ Halle, Dept Psychiat, Halle, Germany Univ Munich, Dept Psychiat, D-80539 Munich, Germany Univ Iceland, Dept Psychiat, Reykjavik, Iceland Landspitali University Hospital Reykjavik, Iceland Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Verona, Sect Psychiat, I-37100 Verona, Italy UCL, Inst Cognit Neurosci, London, England UCL, Mental Hlth Sci Unit, London, England Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

مصطلحات موضوعية: Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Schizophrenia, Sweden

الوصف: To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. ; Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder. ; NIMH R01 MH077139 R01 MH095034 Stanley Center for Psychiatric Research Sylvan Herman Foundation Friedman Brain Institute at the Mount Sinai School of Medicine Karolinska Institutet, Karolinska University Hospital Swedish Research Council Swedish County Council Soderstrom Konigska Foundation Netherlands Scientific Organization NWO 645-000-003 info:eu-repo/grantAgreement/EC/FP7/223423 Danish Strategic Research Council H. Lundbeck A/S Faculty of Health Sciences at Aarhus University Lundbeck Foundation Stanley Research Foundation Wellcome Trust 085475/B/08/Z 085475/Z/08/Z

العلاقة: info:eu-repo/grantAgreement/EC/FP7/223423; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827979/pdf/nihms512111.pdfTest; http://dx.doi.org/10.1038/ng.2742Test; Nat. Genet. 2013, 45(10):1150-9; http://hdl.handle.net/2336/317149Test; Nature genetics

الإتاحة: https://doi.org/10.1038/ng.2742Test
http://hdl.handle.net/2336/317149Test

المؤلفون: Davis, Oliver SP, Band, Gavin, Pirinen, Matti, Haworth, Claire MA, Meaburn, Emma L, Kovas, Yulia, Harlaar, Nicole, Docherty, Sophia J, Hanscombe, Ken B, Trzaskowski, Maciej, Curtis, Charles JC, Strange, Amy, Freeman, Colin, Bellenguez, Céline, Su, Zhan, Pearson, Richard, Vukcevic, Damjan, Langford, Cordelia, Deloukas, Panos, Hunt, Sarah, Gray, Emma, Dronov, Serge, Potter, Simon C, Tashakkori-Ghanbaria, Avazeh, Edkins, Sarah, Bumpstead, Suzannah J, Blackwell, Jenefer M, Bramon, Elvira, Brown, Matthew A, Casas, Juan P, Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz AZ, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Barroso, Ines, Peltonen, Leena, Dale, Philip S, Petrill, Stephen A, Schalkwyk, Leonard S, Craig, Ian W, Lewis, Cathryn M, Price, Thomas S, Wellcome Trust Case Control Consortium 2, Donnelly, Peter, Plomin, Robert, Spencer, Chris CA

الوصف: Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children's ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child's cognitive abilities at age twelve.

وصف الملف: text

العلاقة: https://researchonline.lshtm.ac.uk/id/eprint/1823797/1/ncomms5204-s1.pdfTest; Davis, Oliver SP; Band, Gavin; Pirinen, Matti; Haworth, Claire MA; Meaburn, Emma L; Kovas, Yulia; Harlaar, Nicole; Docherty, Sophia J; Hanscombe, Ken B; Trzaskowski, Maciej; +43 more. Curtis, Charles JC; Strange, Amy; Freeman, Colin; Bellenguez, Céline; Su, Zhan; Pearson, Richard; Vukcevic, Damjan; Langford, Cordelia; Deloukas, Panos; Hunt, Sarah; Gray, Emma; Dronov, Serge; Potter, Simon C; Tashakkori-Ghanbaria, Avazeh; Edkins, Sarah; Bumpstead, Suzannah J; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A ; Casas, Juan P ; Corvin, Aiden; Duncanson, Audrey; Jankowski, Janusz AZ; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin NA; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Barroso, Ines; Peltonen, Leena; Dale, Philip S; Petrill, Stephen A; Schalkwyk, Leonard S; Craig, Ian W; Lewis, Cathryn M; Price, Thomas S; Wellcome Trust Case Control Consortium 2; Donnelly, Peter; Plomin, Robert; Spencer, Chris CA; (2014) The correlation between reading and mathematics ability at age twelve has a substantial genetic component. Nature communications, 5 (1). 4204-. ISSN 2041-1723 DOI: https://doi.org/10.1038/ncomms5204Test

الإتاحة: https://doi.org/10.1038/ncomms5204Test
https://researchonline.lshtm.ac.uk/id/eprint/1823797Test/
https://researchonline.lshtm.ac.uk/id/eprint/1823797/1/ncomms5204-s1.pdfTest

المؤلفون: Strange, Amy, Bellenguez, Céline, Sim, Xueling, Luben, Robert, Hysi, Pirro G., Ramdas, Wishal D., van Koolwijk, Leonieke M.E., Freeman, Colin, Pirinen, Matti, Su, Zhan, Band, Gavin, Pearson, Richard, Vukcevic, Damjan, Langford, Cordelia, Deloukas, Panos, Hunt, Sarah, Gray, Emma, Dronov, Serge, Potter, Simon C., Tashakkori-Ghanbaria, Avazeh, Edkins, Sarah, Bumpstead, Suzannah J., Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz A.Z., Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N.A., Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J., Trembath, Richard C., Wood, Nicholas W., Barroso, Ines, Leena Peltonen, Leena Peltonen, Healey, Paul, McGuffin, Peter, Topouzis, Fotis, Klaver, Caroline C.W., van Duijn, Cornelia M., Mackey, David A., Young, Terri L., Hammond, Christopher J., Khaw, Kay Tee, Wang, Jie Jin, Wong, Tien Y.

المصدر: Strange , A , Bellenguez , C , Sim , X , Luben , R , Hysi , P G , Ramdas , W D , van Koolwijk , L M E , Freeman , C , Pirinen , M , Su , Z , Band , G , Pearson , R , Vukcevic , D , Langford , C , Deloukas , P , Hunt , S , Gray , E , Dronov , S , Potter , S C , Tashakkori-Ghanbaria , A , Edkins , S , Bumpstead , S J , Blackwell , J M ....

الوصف: To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, P combined = 1.10 × 10 -8 ). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/4afb003f-98f2-46eb-9024-c89b2368f0f0Test

الإتاحة: https://doi.org/10.1093/hmg/ddt293Test
https://pure.eur.nl/en/publications/4afb003f-98f2-46eb-9024-c89b2368f0f0Test
https://pure.eur.nl/ws/files/97680831/Genome-wide_association_study_of_intraocular_pressure_identifies_the_GLCCI1_ICA1_region_as_a_glaucoma_susceptibility_locus.pdfTest
http://www.scopus.com/inward/record.url?scp=84887010281&partnerID=8YFLogxKTest

المؤلفون: Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Kähler, Anna K, Akterin, Susanne, Bergen, Sarah E, Collins, Ann L, Crowley, James J, Fromer, Menachem, Kim, Yunjung, Lee, Sang Hong, Magnusson, Patrik KE, Sanchez, Nick, Stahl, Eli A, Williams, Stephanie, Wray, Naomi R, Xia, Kai, Bettella, Francesco, Borglum, Anders D, Bulik-Sullivan, Brendan K, Cormican, Paul, Craddock, Nick, de Leeuw, Christiaan, Durmishi, Naser, Gill, Michael, Golimbet, Vera, Hamshere, Marian L, Holmans, Peter, Hougaard, David M, Kendler, Kenneth S, Lin, Kuang, Morris, Derek W, Mors, Ole, Mortensen, Preben B, Neale, Benjamin M, O'Neill, Francis A, Owen, Michael J, Milovancevic, Milica Pejovic, Posthuma, Danielle, Powell, John, Richards, Alexander L, Riley, Brien P, Ruderfer, Douglas, Rujescu, Dan, Sigurdsson, Engilbert, Silagadze, Teimuraz, Smit, August B, Stefansson, Hreinn, Steinberg, Stacy, Suvisaari, Jaana, Tosato, Sarah, Verhage, Matthijs, Walters, James T, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Douglas F, Gejman, Pablo V, Laurent, Claudine, Mowry, Bryan J, O'Donovan, Michael C, Pulver, Ann E, Schwab, Sibylle G, Wildenauer, Dieter B, Dudbridge, Frank, Shi, Jianxin, Albus, Margot, Alexander, Madeline, Campion, Dominique, Cohen, David, Dikeos, Dimitris, Duan, Jubao, Eichhammer, Peter, Godard, Stephanie, Hansen, Mark, Lerer, F Bernard, Liang, Kung-Yee, Maier, Wolfgang, Mallet, Jacques, Nertney, Deborah A, Nestadt, Gerald, Norton, Nadine, Papadimitriou, George N, Ribble, Robert, Sanders, Alan R, Silverman, Jeremy M, Walsh, Dermot, Williams, Nigel M, Wormley, Brandon, Psychosis Endophenotypes International Consortium, Arranz, Maria J, Bakker, Steven, Bender, Stephan, Bramon, Elvira, Collier, David, Crespo-Facorro, Benedicto, Hall, Jeremy, Iyegbe, Conrad, Jablensky, Assen, Kahn, Rene S, Kalaydjieva, Luba, Lawrie, Stephen, Lewis, Cathryn M, Linszen, Don H, Mata, Ignacio, McIntosh, Andrew, Murray, Robin M, Ophoff, Roel A, Van Os, Jim, Walshe, Muriel, Weisbrod, Matthias, Wiersma, Durk, Wellcome Trust Case Control Consortium 2, Donnelly, Peter, Barroso, Ines, Blackwell, Jenefer M, Brown, Matthew A, Casas, Juan P, Corvin, Aiden P, Deloukas, Panos, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S, Mathew, Christopher G, Palmer, Colin NA, Plomin, Robert, Rautanen, Anna, Sawcer, Stephen J, Trembath, Richard C, Viswanathan, Ananth C, Wood, Nicholas W, Spencer, Chris CA, Band, Gavin, Bellenguez, Céline, Freeman, Colin, Hellenthal, Garrett, Giannoulatou, Eleni, Pirinen, Matti, Pearson, Richard D, Strange, Amy, Su, Zhan, Vukcevic, Damjan, Langford, Cordelia, Hunt, Sarah E, Edkins, Sarah, Gwilliam, Rhian, Blackburn, Hannah, Bumpstead, Suzannah J, Dronov, Serge, Gillman, Matthew, Gray, Emma, Hammond, Naomi, Jayakumar, Alagurevathi, McCann, Owen T, Liddle, Jennifer, Potter, Simon C, Ravindrarajah, Radhi, Ricketts, Michelle, Tashakkori-Ghanbaria, Avazeh, Waller, Matthew J, Weston, Paul, Widaa, Sara, Whittaker, Pamela, McCarthy, Mark I, Stefansson, Kari, Scolnick, Edward, Purcell, Shaun, McCarroll, Steven A, Sklar, Pamela, Hultman, Christina M, Sullivan, Patrick F

الوصف: Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

وصف الملف: text

العلاقة: https://researchonline.lshtm.ac.uk/id/eprint/4652869/1/Genome-wide%20association%20analysis%20identifies%2013%20new%20risk%20loci%20for%20schizophrenia.pdfTest; Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah E; Collins, Ann L; Crowley, James J; Fromer, Menachem; +180 more. Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik KE; Sanchez, Nick; Stahl, Eli A; Williams, Stephanie; Wray, Naomi R; Xia, Kai; Bettella, Francesco; Borglum, Anders D; Bulik-Sullivan, Brendan K; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L; Holmans, Peter; Hougaard, David M; Kendler, Kenneth S; Lin, Kuang; Morris, Derek W; Mors, Ole; Mortensen, Preben B; Neale, Benjamin M; O'Neill, Francis A; Owen, Michael J; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L; Riley, Brien P; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T; Multicenter Genetic Studies of Schizophrenia Consortium; Levinson, Douglas F; Gejman, Pablo V; Kendler, Kenneth S; Laurent, Claudine; Mowry, Bryan J; O'Donovan, Michael C; Owen, Michael J; Pulver, Ann E; Riley, Brien P; Schwab, Sibylle G; Wildenauer, Dieter B; Dudbridge, Frank ; Holmans, Peter; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A; Nestadt, Gerald; Norton, Nadine; O'Neill, Francis A; Papadimitriou, George N; Ribble, Robert; Sanders, Alan R; Silverman, Jeremy M; Walsh, Dermot; Williams, Nigel M; Wormley, Brandon; Psychosis Endophenotypes International Consortium; Arranz, Maria J; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M; Lin, Kuang; Linszen, Don H; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M; Ophoff, Roel A; Powell, John; Rujescu, Dan; Van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Wellcome Trust Case Control Consortium 2; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M; Bramon, Elvira; Brown, Matthew A; Casas, Juan P; Corvin, Aiden P; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S; Mathew, Christopher G; Palmer, Colin NA; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J; Trembath, Richard C; Viswanathan, Ananth C; Wood, Nicholas W; Spencer, Chris CA; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T; Liddle, Jennifer; Potter, Simon C; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G; Blackwell, Jenefer M; Brown, Matthew A; Corvin, Aiden P; McCarthy, Mark I; Spencer, Chris CA; Bramon, Elvira; Corvin, Aiden P; O'Donovan, Michael C; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A; Sklar, Pamela; Hultman, Christina M; Sullivan, Patrick F; (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature genetics, 45 (10). pp. 1150-1159. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.2742Test

الإتاحة: https://doi.org/10.1038/ng.2742Test
https://researchonline.lshtm.ac.uk/id/eprint/4652869Test/
https://researchonline.lshtm.ac.uk/id/eprint/4652869/1/Genome-wide%20association%20analysis%20identifies%2013%20new%20risk%20loci%20for%20schizophrenia.pdfTest