| Biological insights from 108 schizophrenia-associated genetic loci | |
Ripke, Stephan1,2; Neale, Benjamin M.1,2,3,4; Corvin, Aiden5; Walters, James T. R.6; Farh, Kai-How1; Holmans, Peter A.6,7; Lee, Phil1,2,4; Bulik-Sullivan, Brendan1,2; Collier, David A.8,9; Huang, Hailiang1,3; Pers, Tune H.3,10,11,12; Agartz, Ingrid13,14,15; Agerbo, Esben16,17,18; Albus, Margot19; Alexander, Madeline20; Amin, Farooq21,22; Bacanu, Silviu A.23; Begemann, Martin24; Belliveau, Richard A., Jr.2; Bene, Judit25,26; Bergen, Sarah E.2,27; Bevilacqua, Elizabeth2; Bigdeli, Tim B.23; Black, Donald W.28; Bruggeman, Richard29; Buccola, Nancy G.30; Buckner, Randy L.31,32,33; Byerley, William34; Cahn, Wiepke35; Cai, Guiqing36,37; Campion, Dominique38,39; Cantor, Rita M.40; Carr, Vaughan J.41,42; Carrera, Noa6; Catts, Stanley V.41,43; Chambert, Kimberly D.2; Chan, Raymond C. K.44 ; Chen, Ronald Y. L.45; Chen, Eric Y. H.45,46; Cheng, Wei47; Cheung, Eric F. C.48; Chong, Siow Ann49; Cloninger, C. Robert50; Cohen, David51,52; Cohen, Nadine53; Cormican, Paul5; Craddock, Nick6,7; Crowley, James J.54; Curtis, David55,56; Davidson, Michael57; Davis, Kenneth L.37; Degenhardt, Franziska58,59; Del Favero, Jurgen60; Demontis, Ditte18,61,62; Dikeos, Dimitris63; Dinan, Timothy64; Djurovic, Srdjan15,65; Donohoe, Gary5,66,67; Drapeau, Elodie37; Duan, Jubao68,69; Dudbridge, Frank70; Durmishi, Naser71; Eichhammer, Peter72; Eriksson, Johan73,74,75,76; Escott-Price, Valentina6; Essioux, Laurent77; Fanous, Ayman H.78,79,80,81; Farrell, Martilias S.54; Frank, Josef82; Franke, Lude83; Freedman, Robert84; Freimer, Nelson B.85; Friedl, Marion86; Friedman, Joseph I.37; Fromer, Menachem1,2,4,87; Genovese, Giulio2; Georgieva, Lyudmila6; Giegling, Ina86,88; Giusti-Rodriguez, Paola54; Godard, Stephanie89,90; Goldstein, Jacqueline I.1,3; Golimbet, Vera91; Gopal, Srihari92; Gratten, Jacob93; de Haan, Lieuwe94; Hammer, Christian24; Hamshere, Marian L.6; Hansen, Mark95; Hansen, Thomas18,96; Haroutunian, Vahram37,97,98; Hartmann, Annette M.86; Henskens, Frans A.41,99,100; Herms, Stefan58,59,101; Hirschhorn, Joel N.3,11,12,102; Hoffmann, Per58,59,101; Hofman, Andrea58,59; Hollegaard, Mads V.103; Hougaard, David M.103; Ikeda, Masashi104; Joa, Inge105; Julia, Antonio106; Kahn, Rene S.35; Kalaydjieva, Luba107,108; Karachanak-Yankova, Sena109; Karjalainen, Juha83; Kavanagh, David6; Keller, Matthew C.110; Kennedy, James L.111,112,113; Khrunin, Andrey114; Kim, Yunjung54; Klovins, Janis115; Knowles, James A.116,117; Konte, Bettina86; Kucinskas, Vaidutis118; Kucinskiene, Zita Ausrele118; Kuzelova-Ptackova, Hana119,120; Kahler, Anna K.27; Laurent, Claudine20,121; Keong, Jimmy Lee Chee49,122; Lee, S. Hong93; Legge, Sophie E.6; Lerer, Bernard123; Li, Miaoxin45,46,124; Li, Tao125,126; Liang, Kung-Yee127; Lieberman, Jeffrey128; Limborska, Svetlana114; Loughland, Carmel M.41,129; Lubinski, Jan130; Lonnqvist, Jouko131; Macek, Milan, Jr.119,120; Magnusson, Patrik K. E.27; Maher, Brion S.132; Maier, Wolfgang133; Mallet, Jacques134; Marsal, Sara106; Mattheisen, Manuel18,61,62,135; Mattingsdal, Morten15,136; McCarley, Robert W.137,138; McDonald, Colm139; McIntosh, Andrew M.140,141; Meier, Sandra82; Meijer, Carin J.94; Melegh, Bela25,26; Melle, Ingrid15,142; Mesholam-Gately, Raquelle I.137,143; Metspalu, Andres144; Michie, Patricia T.41,145; Milani, Lili144; Milanova, Vihra146; Mokrab, Younes8; Morris, Derek W.5,66,67; Mors, Ole18,61,147; Murphy, Kieran C.148; Murray, Robin M.149; Myin-Germeys, Inez150; Mueller-Myhsok, Bertram151,152,153; Nelis, Mari144; Nenadic, Igor154; Nertney, Deborah A.155,156; Nestadt, Gerald157; Nicodemus, Kristin K.158; Nikitina-Zake, Liene115; Nisenbaum, Laura159; Nordin, Annelie160; O'Callaghan, Eadbhard161; O'Dushlaine, Colm2; O'Neill, F. Anthony162; Oh, Sang-Yun163; Olincy, Ann84; Olsen, Line18,96; Van Os, Jim150,164; Pantelis, Christos41,165,166; Papadimitriou, George N.63; Papiol, Sergi24; Parkhomenko, Elena37; Pato, Michele T.116,117; Paunio, Tiina167,168; Pejovic-Milovancevic, Milica169; Perkins, Diana O.170; Pietilainen, Olli168,171; Pimm, Jonathan56; Pocklington, Andrew J.6; Powell, John149; Price, Alkes3,172; Pulver, Ann E.157; Purcell, Shaun M.87; Quested, Digby173; Rasmussen, Henrik B.18,96; Reichenberg, Abraham37; Reimers, Mark A.174; Richards, Alexander L.6; Roffman, Joshua L.31,33; Roussos, Panos87,175; Ruderfer, Douglas M.6,87; Salomaa, Veikko76; Sanders, Alan R.68,69; Schall, Ulrich41,129; Schubert, Christian R.176; Schulze, Thomas G.82,177; Schwab, Sibylle G.178; Scolnick, Edward M.2; Scott, Rodney J.41,179,180; Seidman, Larry J.137,143; Shi, Jianxin181; Sigurdsson, Engilbert182; Silagadze, Teimuraz183; Silverman, Jeremy M.37,184; Sim, Kang49; Slominsky, Petr114; Smoller, Jordan W.2,4; So, Hon-Cheong45; Spencer, Chris C. A.185; Stahl, Eli A.3,87; Stefansson, Hreinn186; Steinberg, Stacy186; Stogmann, Elisabeth187; Straub, Richard E.188; Strengman, Eric35,189; Strohmaier, Jana82; Stroup, T. Scott128; Subramaniam, Mythily49; Suvisaari, Jaana131; Svrakic, Dragan M.50; Szatkiewicz, Jin P.54; Soderman, Erik13; Thirumalai, Srinivas190; Toncheva, Draga109; Tosato, Sarah191; Veijola, Juha192,193; Waddington, John194; Walsh, Dermot195; Wang, Dai92; Wang, Qiang125,126; Webb, Bradley T.23; Weiser, Mark57; Wildenauer, Dieter B.196; Williams, Nigel M.6; Williams, Stephanie54; Witt, Stephanie H.82; Wolen, Aaron R.174; Wong, Emily H. M.45; Wormley, Brandon K.23; Xi, Hualin Simon197; Zai, Clement C.111,112; Zheng, Xuebin198; Zimprich, Fritz187; Wray, Naomi R.93; Stefansson, Kari186; Visscher, Peter M.93; Adolfsson, Rolf160; Andreassen, Ole A.15,142; Blackwood, Douglas H. R.141; Bramon, Elvira199; Buxbaum, Joseph D.36,37,97,200; Borglum, Anders D.18,61,62,147; Cichon, Sven58,59,101,201; Darvasi, Ariel202; Domenici, Enrico203; Ehrenreich, Hannelore24; Esko, Tonu3,11,12,102,144; Gejman, Pablo V.68,69; Gill, Michael5; Gurling, Hugh56; Hultman, Christina M.27; Iwata, Nakao104; Jablensky, Assen V.41,108,196,204; Jonsson, Erik G.13,15; Kendler, Kenneth S.205,206; Kirov, George6; Knight, Jo111,112,113; Lencz, Todd207,208,209; Levinson, Douglas F.20; Li, Qingqin S.92; Liu, Jianjun198,210; Malhotra, Anil K.207,208,209; McCarroll, Steven A.2,102; McQuillin, Andrew56; Moran, Jennifer L.2; Mortensen, Preben B.16,17,18; Mowry, Bryan J.93,211; Noethen, Markus M.58,59; Ophoff, Roel A.35,40,85; Owen, Michael J.6,7; Palotie, Aarno2,4,171; Pato, Carlos N.116,117; Petryshen, Tracey L.2,137,212,213; Posthuma, Danielle214,215,216; Rietschel, Marcella82; Riley, Brien P.205,206; Rujescu, Dan86,88; Sham, Pak C.45,46,124; Sklar, Pamela87,97,175; St Clair, David217; Weinberger, Daniel R.188,218,219,220,221; Wendland, Jens R.176; Werge, Thomas18,96,222; Daly, Mark J.1,2,3; Sullivan, Patrick F.27,54,170; O'Donovan, Michael C.6,7; Psychiat Genomics Consortium; Psychosis Endophenotypes Int Conso; Wellcome Trust Case-Control Consor
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| 摘要 | 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 new insights into aetiology, but associations at DRD2 and several 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 have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia. |
| 2014-07-24 | |
| 语种 | 英语 |
| 发表期刊 | NATURE
 |
| ISSN | 0028-0836 |
| 卷号 | 511期号:7510页码:421-+ |
| 期刊论文类型 | Article |
| 收录类别 | SCI |
| WOS记录号 | WOS:000339335700037 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.psych.ac.cn/handle/311026/14207 |
| 专题 | 健康与遗传心理学研究室 |
| 作者单位 | 1.Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA 2.Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA 3.Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA 4.Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA 5.Univ Ireland Trinity Coll, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland 6.Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Inst Psychol Med & Clin Neurosci, Cardiff CF24 4HQ, S Glam, Wales 7.Cardiff Univ, Natl Ctr Mental Hlth, Cardiff CF24 4HQ, S Glam, Wales 8.Eli Lilly & Co Ltd, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England 9.Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England 10.Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark 11.Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA 12.Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 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| 推荐引用方式 GB/T 7714 | Ripke, Stephan,Neale, Benjamin M.,Corvin, Aiden,et al. Biological insights from 108 schizophrenia-associated genetic loci[J]. NATURE,2014,511(7510):421-+. |
| APA | Ripke, Stephan.,Neale, Benjamin M..,Corvin, Aiden.,Walters, James T. R..,Farh, Kai-How.,...&Wellcome Trust Case-Control Consor.(2014).Biological insights from 108 schizophrenia-associated genetic loci.NATURE,511(7510),421-+. |
| MLA | Ripke, Stephan,et al."Biological insights from 108 schizophrenia-associated genetic loci".NATURE 511.7510(2014):421-+. |
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