Biological insights from 108 schizophrenia-associated genetic loci.
Biological insights from 108 schizophrenia-associated genetic loci.
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DOI：
10.1038/nature13595
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发表时间：
2014-07-24
期刊：
影响因子：
64.8
通讯作者：
O'Donovan, Michael C.
中科院分区：
文献类型：
--
作者：
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, Kimberly D.;Chan, Raymond C. K.;Chen, Ronald Y. L.;Chen, Eric Y. H.;Cheng, Wei;Cheung, Eric F. C.;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-Rodriguez, 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;Julia, Antonio;Kahn, Rene 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;Kahler, Anna K.;Laurent, Claudine;Keong, Jimmy Lee Chee;Lee, S. Hong;Legge, Sophie E.;Lerer, Bernard;Li, Miaoxin;Li, Tao;Liang, Kung-Yee;Lieberman, Jeffrey;Limborska, Svetlana;Loughland, Carmel M.;Lubinski, Jan;Lonnqvist, Jouko;Macek, Milan, Jr.;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;Mueller-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.;Pietilainen, 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.;Soderman, 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.;Borglum, Anders D.;Cichon, Sven;Darvasi, Ariel;Domenici, Enrico;Ehrenreich, Hannelore;Esko, Tonu;Gejman, Pablo V.;Gill, Michael;Gurling, Hugh;Hultman, Christina M.;Iwata, Nakao;Jablensky, Assen V.;Jonsson, 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.;Noethen, 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.
精神分裂症是一种高度遗传的疾病。遗传风险由大量等位基因赋予，包括可能通过全基因组关联研究检测到的影响小的常见等位基因。在这里，我们报告了一项多阶段精神分裂症全基因组关联研究，涉及多达36，989例病例和113，075例对照。我们确定了128个独立的协会，跨越108个保守定义的基因座，满足全基因组意义，其中83个以前没有报道过。在大脑中表达的基因之间的关联丰富，为研究结果提供了生物学上的可验证性。许多研究结果有可能为病因学提供全新的见解，但DRD2和参与神经递质神经传递的多个基因的关联突出了与精神分裂症具有已知和潜在治疗相关性的分子，并且与领先的病理生理学假设一致。独立于大脑中表达的基因，在免疫中起重要作用的组织中表达的基因之间的关联是丰富的，为免疫系统和精神分裂症之间的假设联系提供了支持。
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here, we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain providing biological plausibility for the findings. Many findings have the potential to provide entirely novel insights into aetiology, but associations at DRD2 and multiple genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that play important roles in immunity, providing support for the hypothesized link between the immune system and schizophrenia.
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影响因子：
6.9
作者：
Lichtenstein, Paul;Bjork, Camilla;Sullivan, Patrick F.
通讯作者：
Sullivan, Patrick F.
DOI：
10.1126/science.1222794
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Maurano MT;Humbert R;Rynes E;Thurman RE;Haugen E;Wang H;Reynolds AP;Sandstrom R;Qu H;Brody J;Shafer A;Neri F;Lee K;Kutyavin T;Stehling-Sun S;Johnson AK;Canfield TK;Giste E;Diegel M;Bates D;Hansen RS;Neph S;Sabo PJ;Heimfeld S;Raubitschek A;Ziegler S;Cotsapas C;Sotoodehnia N;Glass I;Sunyaev SR;Kaul R;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
30.8
作者：
Ferreira, Manuel A. R.;O'Donovan, Michael C.;Meng, Yan A.;Jones, Ian R.;Ruderfer, Douglas M.;Jones, Lisa;Fan, Jinbo;Kirov, George;Perlis, Roy H.;Green, Elaine K.;Smoller, Jordan W.;Grozeva, Detelina;Stone, Jennifer;Nikolov, Ivan;Chambert, Kimberly;Hamshere, Marian L.;Nimgaonkar, Vishwajit L.;Moskvina, Valentina;Thase, Michael E.;Caesar, Sian;Sachs, Gary S.;Franklin, Jennifer;Gordon-Smith, Katherine;Ardlie, Kristin G.;Gabriel, Stacey B.;Fraser, Christine;Blumenstiel, Brendan;Defelice, Matthew;Breen, Gerome;Gill, Michael;Morris, Derek W.;Elkin, Amanda;Muir, Walter J.;McGhee, Kevin A.;Williamson, Richard;MacIntyre, Donald J.;MacLean, Alan W.;Clair, David St;Robinson, Michelle;Van Beck, Margaret;Pereira, Ana C. P.;Kandaswamy, Radhika;McQuillin, Andrew;Collier, David A.;Bass, Nicholas J.;Young, Allan H.;Lawrence, Jacob;Ferrier, I. Nicol;Anjorin, Adebayo;Farmer, Anne;Curtis, David;Scolnick, Edward M.;McGuffin, Peter;Daly, Mark J.;Corvin, Aiden P.;Holmans, Peter A.;Blackwood, Douglas H.;Gurling, Hugh M.;Owen, Michael J.;Purcell, Shaun M.;Sklar, Pamela;Craddock, Nick
通讯作者：
Craddock, Nick
影响因子：
11
作者：
Lips, E. S.;Cornelisse, L. N.;Toonen, R. F.;Min, J. L.;Hultman, C. M.;Holmans, P. A.;O'Donovan, M. C.;Purcell, S. M.;Smit, A. B.;Verhage, M.;Sullivan, P. F.;Visscher, P. M.;Posthuma, D.
通讯作者：
Posthuma, D.
影响因子：
11
作者：
Hamshere ML;Walters JT;Smith R;Richards AL;Green E;Grozeva D;Jones I;Forty L;Jones L;Gordon-Smith K;Riley B;O'Neill FA;Kendler KS;Sklar P;Purcell S;Kranz J;Schizophrenia Psychiatric Genome-wide Association Study Consortium;Wellcome Trust Case Control Consortium+;Wellcome Trust Case Control Consortium 2;Morris D;Gill M;Holmans P;Craddock N;Corvin A;Owen MJ;O'Donovan MC
通讯作者：
O'Donovan MC