Biological insights from 108 schizophrenia-associated genetic loci

Elodie, Drapeau; Ripke, Stephan; Th, Pers; Walters, James T. R.; Rc, Chan; Ry, Chen; Sa, Bacanu; Ra, Belliveau Jr; Rs, Kahn; Se, Bergen; Robert Cloninger, C.; Sh, Lee; Se, Legge; Tb, Bigdeli; Rw, McCarley; Ri, Mesholam Gately; Pt, Michie; Rl, Buckner; Rm, Murray; Rm, Cantor; Sm, Purcell; Vj, Carr; Sv, Catts; Sa, Chong; Tg, Schulze; Sg, Schwab; Rj, Scott; Sy, Oh; Re, Straub; Ts, Stroup; Sh, Witt; Neale, Benjamin M.; Corvin, Aiden; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Scott Stroup, T.; de Haan, Lieuwe; Huang, Hailiang; Pers, Tune H.; Söderman, Erik; Pv, Gejman; Simon Xi, Hualin; Qs, Li; Trust Case-Control Consortium, Wellcome; Sa, McCarroll; Rck, Chan; Ra, Ophoff; Ryl, Chen; Tl, Petryshen; Weinberger, David R.; Wellcome Trust Case Control Consortium, 2.; Cormican, Paul; Jt, Walters; Craddock, Nick; Kh, Farh; Crowley, James J.; Curtis, David; Davidson, Michael; Consortium, Schizophrenia Working Group of the Psychiatric Genomics; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Pke, Magnusson; Donohoe, Gary; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Ey, Chen; Eichhammer, Peter; Van Os, Jim; Eriksson, Johan; Escott-Price, Valentina; Ef, Cheung; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Mc, Keller; Freedman, Robert; Price, Alkes; Freimer, Nelson B.; Pulver, Ann E.; Jl, Kennedy; Friedl, Marion; Purcell, Shaun M.; Friedman, Joseph I.; Quested, Digby; Fromer, Menachem; Muller Myhsok, B.; Rasmussen, Henrik B.; Genovese, Giulio; Reichenberg, Abraham; Georgieva, Lyudmila; Reimers, Mark A.; Giegling, Ina; Richards, Alexander L.; Giusti-Rodríguez, Paola; Roffman, Joshua L.; Godard, Stephanie; Roussos, Panos; Ruderfer, Douglas M.; Ja, Knowles; Goldstein, Jacqueline I.; Golimbet, Vera; Salomaa, Veikko; Sanders, Alan R.; Gopal, Srihari; Gratten, Jacob; Schall, Ulrich; Schubert, Christian R.; Hammer, Christian; Schulze, Thomas G.; Hamshere, Marian L.; Schwab, Sibylle G.; Hansen, Mark; Scolnick, Edward M.; Scott, Rodney J.; Hansen, Thomas; Seidman, Larry J.; Haroutunian, Vahram; Dw, Black; Shi, Jianxin; Hartmann, Annette M.; Sigurdsson, Engilbert; Henskens, Frans A.; Silagadze, Teimuraz; Herms, Stefan; Silverman, Jeremy M.; Sim, Kang; Hirschhorn, Joel N.; Slominsky, Petr; Hoffmann, Per; Smoller, Jordan W.; Hofman, Andrea; So, Hon-Cheong; Ng, Buccola; Hollegaard, Mads V.; Spencer, Chris ChrisC A.; Soderman, Erik; Hougaard, David M.; Stahl, Eli A.; Stefansson, Hreinn; Ikeda, Masashi; Steinberg, Stacy; Joa, Inge; Stogmann, Elisabeth; Julià, Antonio; Straub, Richard E.; Kahn, René S.; Strengman, Eric; Strohmaier, Jana; Jl, Roffman; Kalaydjieva, Luba; Stroup, T. Scott; Karachanak-Yankova, Sena; Subramaniam, Mythily; Karjalainen, Juha; Suvisaari, Jaana; Kavanagh, David; Svrakic, Dragan M.; Keller, Matthew C.; Szatkiewicz, Jin P.; Kennedy, James L.; Thirumalai, Srinivas; Dw, Morris; Kim, Yunjung; Toncheva, Draga; Tosato, Sarah; Klovins, Janis; Veijola, Juha; Knowles, James A.; Kc, Murphy; Waddington, John; Walsh, Dermot; Konte, Bettina; Kucinskiene, Zita Ausrele; Wang, Dai; De Haan, L.; Kucinskas, Vaidutis; Wang, Qiang; Webb, Bradley T.; Lonnqvist, Jouko; Kuzelova-Ptackova, Hana; Da, Nertney; Weiser, Mark; Keong, Jimmy Lee Chee; Wildenauer, Dieter B.; Kahler, Anna K.; Williams, Nigel M.; Kk, Nicodemus; Williams, Stephanie; Laurent, Claudine; Lee, S. Hong; Witt, Stephanie H.; Wolen, Aaron R.; Legge, Sophie E.; Wong, Emily H. M.; Lerer, Bernard; Wormley, Brandon K.; Fa, O'Neill; Li, Miaoxin; Li, Tao; Xi, Hualin Simon; Zai, Clement C.; Liang, Kung-Yee; Jl, Keong; Zheng, Xuebin; Lieberman, Jeffrey; Zimprich, Fritz; Limborska, Svetlana; Khrunin, Audrey; Wray, Naomi R.; Stefansson, Kari; Loughland, Carmel M.; Gn, Papadimitriou; Visscher, Peter M.; Lubinski, Jan; Macek, Milan; Ky, Liang; Magnusson, Patrik K. E.; Maher, Brion S.; Mt, Pato; Maier, Wolfgang; Mallet, Jacques; Do, Perkins; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; Consortium, Psychosis Endophenotypes International; Jr, Macek M.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Lee Chee Keong, Jimmy; Meijer, Carin J.; Melegh, Bela; Hong Lee, S.; Kähler, Anna K.; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Pk, Magnusson; Michie, Patricia T.; Milani, Lili; Pa, Holmans; Mokrab, Younes; Morris, Derek W.; Rietschel, Marcella; Mors, Ole; Riley, Brien P.; Rujescu, Dan; Murphy, Kieran C.; Sham, Pak C.; Murray, Robin M.; Sklar, Pamela; Myin-Germeys, Inez; St Clair, David; Hb, Rasmussen; Nelis, Mari; Wendland, Jens R.; Nenadic, Igor; Werge, Thomas; Lönnqvist, Jouko; Nertney, Deborah A.; Sullivan, Patrick F.; Kd, Chambert; Nestadt, Gerald; Ma, Reimers; Nicodemus, Kristin K.; Melle, Iingrid; Nikitina-Zake, Liene; Nisenbaum, Laura; O'Callaghan, Eadbhard; O'Neill, F. Anthony; Nordin, Annelie; Ehm, Wong; O'Dushlaine, Colm; Dm, Ruderfer; Oh, Sang-Yun; Milanova, Virha; Olincy, Ann; Olsen, Line; Da, Collier; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Cr, Schubert; Parkhomenko, Elena; Pato, Michele T.; Cr, Cloninger; Paunio, Tiina; Pejovic-Milovancevic, Milica; Em, Scolnick; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Jj, Crowley; Pocklington, Andrew J.; Powell, John; Müller-Myhsok, Bertram; Lj, Seidman; Consortium, Wellcome Trust Case-Control; Kl, Davis; O’Callaghan, Eadbhard; Jm, Silverman; O’Dushlaine, Colm; O’Neill, F. Anthony; Dhr, Blackwood; Jw, Smoller; Ea, Stahl; Endophenotypes International Consortium, Psychosis; Ms, Farrell; Dm, Svrakic; Jp, Szatkiewicz; Nb, Freimer; Ji, Friedman; Ji, Goldstein; Db, Wildenauer; Nm, Williams; Ml, Hamshere; Fa, Henskens; Hs, Xi; Jn, Hirschhorn; Mv, Hollegaard; Dm, Hougaard; Nr, Wray; Pm, Visscher; Oa, Andreassen; Jl, Moran; Jd, Buxbaum; Hc, So; Consortium, Welcome Trust Case-Control; Eg, Jonsson; Jr, Wendland; Ks, Kendler; Jtr, Walters; Df, Levinson; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Mc, O'Donovan; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Eh, Wong; Hultman, Christina M.; Iwata, Nakao; Pb, Mortensen; Jonsson, Erik G.; Jablensky, Assen V.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Mm, Nothen; Lencz, Todd; Levinson, Douglas F.; Jönsson, Erik G.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; Mj, Owen; McQuillin, Andrew; Moran, Jennifer L.; Eyh, Chen; Mortensen, Preben B.; Mowry, Bryan J.; Noethen, Markus M.; Ophoff, Roel A.; Efc, Cheung; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Dh, Blackwood; Petryshen, Tracey L.; Nöthen, Markus M.; Posthuma, Danielle; Pc, Sham; Dr, Weinberger; Mj, Daly; Pf, Sullivan; Daly, Mark J.; O'Donovan, Michael C.; O’Donovan, Michael C.; Bulik-Sullivan, Brendan; Collier, David A.; 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.; 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; Bm, Neale; Cohen, Nadine; Agartz, Iingrid; Ann Chong, Siow; Ak, Kahler; Cm, Loughland; Bs, Maher; Am, McIntosh; Cj, Meijer; Cca, Spencer; Ausrele Kucinskiene, Zita; Aj, Pocklington; Ae, Pulver; Al, Richards; Ar, Sanders; Ah, Fanous; Bt, Webb; Ar, Wolen; Am, Hartmann; Bk, Wormley; Cc, Zai; Anthony O’Neill, F.; Ad, Borglum; Ca, Spencer; Adolfsson, Rolf; Cm, Hultman; Av, Jablensky; Andreassen, Ole A.; Blackwood, Douglas H. R.; Bramon, Elvira; Borglum, Anders D.; Buxbaum, Joseph D.; Cichon, Sven; Ak, Malhotra; Børglum, Anders D.; Bj, Mowry; Cn, Pato; Bp, Riley; Consortium, Psychiat Genomics; Conso, Psychosis Endophenotypes Int; Consor, Wellcome Trust Case-Control

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Timothy Dinan
Elodie et al., 2014

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Nature Research, Nature, 7510(511), p. 421-427, 2014

DOI: 10.1038/nature13595

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@article{Elodie2014,
  abstract = {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.},
  author = {Elodie, Drapeau and Ripke, Stephan and Th, Pers and Walters, James T. R. and Rc, Chan and Ry, Chen and Sa, Bacanu and Ra, Belliveau Jr and Rs, Kahn and Se, Bergen and Robert Cloninger, C. and Sh, Lee and Se, Legge and Tb, Bigdeli and Rw, McCarley and Ri, Mesholam Gately and Pt, Michie and Rl, Buckner and Rm, Murray and Rm, Cantor and Sm, Purcell and Vj, Carr and Sv, Catts and Sa, Chong and Tg, Schulze and Sg, Schwab and Rj, Scott and Sy, Oh and Re, Straub and Ts, Stroup and Sh, Witt and Neale, Benjamin M. and Corvin, Aiden and Farh, Kai-How and Holmans, Peter A. and Lee, Phil and Scott Stroup, T. and de Haan, Lieuwe and Huang, Hailiang and Pers, Tune H. and Söderman, Erik and Pv, Gejman and Simon Xi, Hualin and Qs, Li and Trust Case-Control Consortium, Wellcome and Sa, McCarroll and Rck, Chan and Ra, Ophoff and Ryl, Chen and Tl, Petryshen and Weinberger, David R. and Wellcome Trust Case Control Consortium, 2. and Cormican, Paul and Jt, Walters and Craddock, Nick and Kh, Farh and Crowley, James J. and Curtis, David and Davidson, Michael and Consortium, Schizophrenia Working Group of the Psychiatric Genomics and Davis, Kenneth L. and Degenhardt, Franziska and Del Favero, Jurgen and Demontis, Ditte and Dikeos, Dimitris and Dinan, Timothy and Djurovic, Srdjan and Pke, Magnusson and Donohoe, Gary and Duan, Jubao and Dudbridge, Frank and Durmishi, Naser and Ey, Chen and Eichhammer, Peter and Van Os, Jim and Eriksson, Johan and Escott-Price, Valentina and Ef, Cheung and Essioux, Laurent and Fanous, Ayman H. and Farrell, Martilias S. and Frank, Josef and Franke, Lude and Mc, Keller and Freedman, Robert and Price, Alkes and Freimer, Nelson B. and Pulver, Ann E. and Jl, Kennedy and Friedl, Marion and Purcell, Shaun M. and Friedman, Joseph I. and Quested, Digby and Fromer, Menachem and Muller Myhsok, B. and Rasmussen, Henrik B. and Genovese, Giulio and Reichenberg, Abraham and Georgieva, Lyudmila and Reimers, Mark A. and Giegling, Ina and Richards, Alexander L. and Giusti-Rodríguez, Paola and Roffman, Joshua L. and Godard, Stephanie and Roussos, Panos and Ruderfer, Douglas M. and Ja, Knowles and Goldstein, Jacqueline I. and Golimbet, Vera and Salomaa, Veikko and Sanders, Alan R. and Gopal, Srihari and Gratten, Jacob and Schall, Ulrich and Schubert, Christian R. and Hammer, Christian and Schulze, Thomas G. and Hamshere, Marian L. and Schwab, Sibylle G. and Hansen, Mark and Scolnick, Edward M. and Scott, Rodney J. and Hansen, Thomas and Seidman, Larry J. and Haroutunian, Vahram and Dw, Black and Shi, Jianxin and Hartmann, Annette M. and Sigurdsson, Engilbert and Henskens, Frans A. and Silagadze, Teimuraz and Herms, Stefan and Silverman, Jeremy M. and Sim, Kang and Hirschhorn, Joel N. and Slominsky, Petr and Hoffmann, Per and Smoller, Jordan W. and Hofman, Andrea and So, Hon-Cheong and Ng, Buccola and Hollegaard, Mads V. and Spencer, Chris ChrisC A. and Soderman, Erik and Hougaard, David M. and Stahl, Eli A. and Stefansson, Hreinn and Ikeda, Masashi and Steinberg, Stacy and Joa, Inge and Stogmann, Elisabeth and Julià, Antonio and Straub, Richard E. and Kahn, René S. and Strengman, Eric and Strohmaier, Jana and Jl, Roffman and Kalaydjieva, Luba and Stroup, T. Scott and Karachanak-Yankova, Sena and Subramaniam, Mythily and Karjalainen, Juha and Suvisaari, Jaana and Kavanagh, David and Svrakic, Dragan M. and Keller, Matthew C. and Szatkiewicz, Jin P. and Kennedy, James L. and Thirumalai, Srinivas and Dw, Morris and Kim, Yunjung and Toncheva, Draga and Tosato, Sarah and Klovins, Janis and Veijola, Juha and Knowles, James A. and Kc, Murphy and Waddington, John and Walsh, Dermot and Konte, Bettina and Kucinskiene, Zita Ausrele and Wang, Dai and De Haan, L. and Kucinskas, Vaidutis and Wang, Qiang and Webb, Bradley T. and Lonnqvist, Jouko and Kuzelova-Ptackova, Hana and Da, Nertney and Weiser, Mark and Keong, Jimmy Lee Chee and Wildenauer, Dieter B. and Kahler, Anna K. and Williams, Nigel M. and Kk, Nicodemus and Williams, Stephanie and Laurent, Claudine and Lee, S. Hong and Witt, Stephanie H. and Wolen, Aaron R. and Legge, Sophie E. and Wong, Emily H. M. and Lerer, Bernard and Wormley, Brandon K. and Fa, O'Neill and Li, Miaoxin and Li, Tao and Xi, Hualin Simon and Zai, Clement C. and Liang, Kung-Yee and Jl, Keong and Zheng, Xuebin and Lieberman, Jeffrey and Zimprich, Fritz and Limborska, Svetlana and Khrunin, Audrey and Wray, Naomi R. and Stefansson, Kari and Loughland, Carmel M. and Gn, Papadimitriou and Visscher, Peter M. and Lubinski, Jan and Macek, Milan and Ky, Liang and Magnusson, Patrik K. E. and Maher, Brion S. and Mt, Pato and Maier, Wolfgang and Mallet, Jacques and Do, Perkins and Marsal, Sara and Mattheisen, Manuel and Mattingsdal, Morten and McCarley, Robert W. and Consortium, Psychosis Endophenotypes International and Jr, Macek M. and McDonald, Colm and McIntosh, Andrew M. and Meier, Sandra and Lee Chee Keong, Jimmy and Meijer, Carin J. and Melegh, Bela and Hong Lee, S. and Kähler, Anna K. and Mesholam-Gately, Raquelle I. and Metspalu, Andres and Pk, Magnusson and Michie, Patricia T. and Milani, Lili and Pa, Holmans and Mokrab, Younes and Morris, Derek W. and Rietschel, Marcella and Mors, Ole and Riley, Brien P. and Rujescu, Dan and Murphy, Kieran C. and Sham, Pak C. and Murray, Robin M. and Sklar, Pamela and Myin-Germeys, Inez and St Clair, David and Hb, Rasmussen and Nelis, Mari and Wendland, Jens R. and Nenadic, Igor and Werge, Thomas and Lönnqvist, Jouko and Nertney, Deborah A. and Sullivan, Patrick F. and Kd, Chambert and Nestadt, Gerald and Ma, Reimers and Nicodemus, Kristin K. and Melle, Iingrid and Nikitina-Zake, Liene and Nisenbaum, Laura and O'Callaghan, Eadbhard and O'Neill, F. Anthony and Nordin, Annelie and Ehm, Wong and O'Dushlaine, Colm and Dm, Ruderfer and Oh, Sang-Yun and Milanova, Virha and Olincy, Ann and Olsen, Line and Da, Collier and Pantelis, Christos and Papadimitriou, George N. and Papiol, Sergi and Cr, Schubert and Parkhomenko, Elena and Pato, Michele T. and Cr, Cloninger and Paunio, Tiina and Pejovic-Milovancevic, Milica and Em, Scolnick and Perkins, Diana O. and Pietiläinen, Olli and Pimm, Jonathan and Jj, Crowley and Pocklington, Andrew J. and Powell, John and Müller-Myhsok, Bertram and Lj, Seidman and Consortium, Wellcome Trust Case-Control and Kl, Davis and O’Callaghan, Eadbhard and Jm, Silverman and O’Dushlaine, Colm and O’Neill, F. Anthony and Dhr, Blackwood and Jw, Smoller and Ea, Stahl and Endophenotypes International Consortium, Psychosis and Ms, Farrell and Dm, Svrakic and Jp, Szatkiewicz and Nb, Freimer and Ji, Friedman and Ji, Goldstein and Db, Wildenauer and Nm, Williams and Ml, Hamshere and Fa, Henskens and Hs, Xi and Jn, Hirschhorn and Mv, Hollegaard and Dm, Hougaard and Nr, Wray and Pm, Visscher and Oa, Andreassen and Jl, Moran and Jd, Buxbaum and Hc, So and Consortium, Welcome Trust Case-Control and Eg, Jonsson and Jr, Wendland and Ks, Kendler and Jtr, Walters and Df, Levinson and Darvasi, Ariel and Domenici, Enrico and Ehrenreich, Hannelore and Mc, O'Donovan and Esko, Tõnu and Gejman, Pablo V. and Gill, Michael and Gurling, Hugh and Eh, Wong and Hultman, Christina M. and Iwata, Nakao and Pb, Mortensen and Jonsson, Erik G. and Jablensky, Assen V. and Kendler, Kenneth S. and Kirov, George and Knight, Jo and Mm, Nothen and Lencz, Todd and Levinson, Douglas F. and Jönsson, Erik G. and Li, Qingqin S. and Liu, Jianjun and Malhotra, Anil K. and McCarroll, Steven A. and Mj, Owen and McQuillin, Andrew and Moran, Jennifer L. and Eyh, Chen and Mortensen, Preben B. and Mowry, Bryan J. and Noethen, Markus M. and Ophoff, Roel A. and Efc, Cheung and Owen, Michael J. and Palotie, Aarno and Pato, Carlos N. and Dh, Blackwood and Petryshen, Tracey L. and Nöthen, Markus M. and Posthuma, Danielle and Pc, Sham and Dr, Weinberger and Mj, Daly and Pf, Sullivan and Daly, Mark J. and O'Donovan, Michael C. and O’Donovan, Michael C. and Bulik-Sullivan, Brendan and Collier, David A. and Agerbo, Esben and Albus, Margot and Alexander, Madeline and Amin, Farooq and Bacanu, Silviu A. and Begemann, Martin and Belliveau, Richard A. and Bene, Judit and Bergen, Sarah E. and Bevilacqua, Elizabeth and Bigdeli, Tim B. and Black, Donald W. and Bruggeman, Richard and Buccola, Nancy G. and Buckner, Randy L. and Byerley, William and Cahn, Wiepke and Cai, Guiqing and Campion, Dominique and Cantor, Rita M. and Carr, Vaughan J. and Carrera, Noa and Catts, Stanley V. and Chambert, Kimberly D. and Chan, Raymond C. K. and Chen, Ronald Y. L. and Chen, Eric Y. H. and Cheng, Wei and Cheung, Eric F. C. and Chong, Siow Ann and Cloninger, C. Robert and Cohen, David and Bm, Neale and Cohen, Nadine and Agartz, Iingrid and Ann Chong, Siow and Ak, Kahler and Cm, Loughland and Bs, Maher and Am, McIntosh and Cj, Meijer and Cca, Spencer and Ausrele Kucinskiene, Zita and Aj, Pocklington and Ae, Pulver and Al, Richards and Ar, Sanders and Ah, Fanous and Bt, Webb and Ar, Wolen and Am, Hartmann and Bk, Wormley and Cc, Zai and Anthony O’Neill, F. and Ad, Borglum and Ca, Spencer and Adolfsson, Rolf and Cm, Hultman and Av, Jablensky and Andreassen, Ole A. and Blackwood, Douglas H. R. and Bramon, Elvira and Borglum, Anders D. and Buxbaum, Joseph D. and Cichon, Sven and Ak, Malhotra and Børglum, Anders D. and Bj, Mowry and Cn, Pato and Bp, Riley and Consortium, Psychiat Genomics and Conso, Psychosis Endophenotypes Int and Consor, Wellcome Trust Case-Control},
  doi = {10.1038/nature13595},
  journal = {Nature},
  month = {jan},
  pages = {421-427},
  title = {Biological insights from 108 schizophrenia-associated genetic loci},
  url = {http://www.nature.com/articles/nature13595.pdf},
  volume = {511},
  year = {2014}
}

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Biological insights from 108 schizophrenia-associated genetic loci

Journal article published in 2014 by Drapeau Elodie, Stephan Ripke, Pers Th, James T. R. Walters, Chan Rc, Chen Ry, Bacanu Sa, Belliveau Jr Ra, Kahn Rs, Bergen Se, C. Robert Cloninger, Lee Sh, Legge Se, Bigdeli Tb, McCarley Rw and other authors. Drapeau Elodie, Stephan Ripke, Pers Th, James T. R. Walters, Chan Rc, Chen Ry, Bacanu Sa, Belliveau Jr Ra, Kahn Rs, Bergen Se, C. Robert Cloninger, Lee Sh, Legge Se, Bigdeli Tb, McCarley Rw, Mesholam Gately Ri, Michie Pt, Buckner Rl, Murray Rm, Cantor Rm, Purcell Sm, Carr Vj, Catts Sv, Chong Sa, Schulze Tg, Schwab Sg, Scott Rj, Oh Sy, Straub Re, Stroup Ts, Witt Sh, Benjamin M. Neale, Aiden Corvin, Kai-How Farh, Peter A. Holmans, Phil Lee, T. Scott Stroup, Lieuwe de Haan, Hailiang Huang, Tune H. Pers, Erik Söderman, Gejman Pv, Hualin Simon Xi, Li Qs, Wellcome Trust Case-Control Consortium, McCarroll Sa, Chan Rck, Ophoff Ra, Chen Ryl, Petryshen Tl, David R. Weinberger, 2. Wellcome Trust Case Control Consortium, Paul Cormican, Walters Jt, Nick Craddock, Farh Kh, James J. Crowley, David Curtis, Michael Davidson, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan

, Srdjan Djurovic, Magnusson Pke, Gary Donohoe, Jubao Duan, Frank Dudbridge, Naser Durmishi, Chen Ey, Peter Eichhammer, Jim Van Os, Johan Eriksson, Valentina Escott-Price

, Cheung Ef, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke

, Keller Mc, Robert Freedman, Alkes Price, Nelson B. Freimer, Ann E. Pulver, Kennedy Jl, Marion Friedl, Shaun M. Purcell, Joseph I. Friedman, Digby Quested, Menachem Fromer, B. Muller Myhsok, Henrik B. Rasmussen, Giulio Genovese, Abraham Reichenberg, Lyudmila Georgieva, Mark A. Reimers, Ina Giegling, Alexander L. Richards, Paola Giusti-Rodríguez, Joshua L. Roffman, Stephanie Godard, Panos Roussos, Douglas M. Ruderfer

, Knowles Ja, Jacqueline I. Goldstein, Vera Golimbet, Veikko Salomaa, Alan R. Sanders, Srihari Gopal, Jacob Gratten, Ulrich Schall

, Christian R. Schubert, Christian Hammer, Thomas G. Schulze, Marian L. Hamshere, Sibylle G. Schwab, Mark Hansen, Edward M. Scolnick, Rodney J. Scott, Thomas Hansen

, Larry J. Seidman, Vahram Haroutunian, Black Dw, Jianxin Shi, Annette M. Hartmann, Engilbert Sigurdsson, Frans A. Henskens, Teimuraz Silagadze, Stefan Herms, Jeremy M. Silverman, Kang Sim, Joel N. Hirschhorn, Petr Slominsky, Per Hoffmann, Jordan W. Smoller, Andrea Hofman, Hon-Cheong So, Buccola Ng, Mads V. Hollegaard, Chris ChrisC A. Spencer, Erik Soderman, David M. Hougaard, Eli A. Stahl, Hreinn Stefansson, Masashi Ikeda, Stacy Steinberg, Inge Joa, Elisabeth Stogmann, Antonio Julià, Richard E. Straub, René S. Kahn, Eric Strengman, Jana Strohmaier, Roffman Jl, Luba Kalaydjieva, T. Scott Stroup, Sena Karachanak-Yankova, Mythily Subramaniam, Juha Karjalainen, Jaana Suvisaari, David Kavanagh, Dragan M. Svrakic, Matthew C. Keller, Jin P. Szatkiewicz, James L. Kennedy, Srinivas Thirumalai, Morris Dw, Yunjung Kim, Draga Toncheva, Sarah Tosato, Janis Klovins, Juha Veijola, James A. Knowles, Murphy Kc, John Waddington, Dermot Walsh, Bettina Konte, Zita Ausrele Kucinskiene, Dai Wang, L. De Haan, Vaidutis Kucinskas, Qiang Wang, Bradley T. Webb, Jouko Lonnqvist, Hana Kuzelova-Ptackova, Nertney Da, Mark Weiser, Jimmy Lee Chee Keong, Dieter B. Wildenauer, Anna K. Kahler, Nigel M. Williams, Nicodemus Kk, Stephanie Williams, Claudine Laurent, S. Hong Lee, Stephanie H. Witt, Aaron R. Wolen, Sophie E. Legge, Emily H. M. Wong, Bernard Lerer, Brandon K. Wormley, O'Neill Fa, Miaoxin Li

, Tao Li, Hualin Simon Xi, Clement C. Zai

, Kung-Yee Liang, Keong Jl, Xuebin Zheng, Jeffrey Lieberman, Fritz Zimprich, Svetlana Limborska, Audrey Khrunin, Naomi R. Wray

, Kari Stefansson, Carmel M. Loughland, Papadimitriou Gn, Peter M. Visscher, Jan Lubinski, Milan Macek, Liang Ky, Patrik K. E. Magnusson, Brion S. Maher, Pato Mt, Wolfgang Maier, Jacques Mallet, Perkins Do, Sara Marsal, Manuel Mattheisen

, Morten Mattingsdal, Robert W. McCarley, Psychosis Endophenotypes International Consortium, Macek M. Jr, Colm McDonald, Andrew M. McIntosh

, Sandra Meier, Jimmy Lee Chee Keong, Carin J. Meijer, Bela Melegh, S. Hong Lee, Anna K. Kähler, Raquelle I. Mesholam-Gately, Andres Metspalu, Magnusson Pk, Patricia T. Michie, Lili Milani, Holmans Pa, Younes Mokrab, Derek W. Morris

, Marcella Rietschel, Ole Mors, Brien P. Riley, Dan Rujescu, Kieran C. Murphy, Pak C. Sham, Robin M. Murray, Pamela Sklar, Inez Myin-Germeys, David St Clair, Rasmussen Hb, Mari Nelis, Jens R. Wendland, Igor Nenadic, Thomas Werge, Jouko Lönnqvist, Deborah A. Nertney, Patrick F. Sullivan, Chambert Kd, Gerald Nestadt, Reimers Ma, Kristin K. Nicodemus, Iingrid Melle, Liene Nikitina-Zake, Laura Nisenbaum, Eadbhard O'Callaghan, F. Anthony O'Neill, Annelie Nordin, Wong Ehm, Colm O'Dushlaine, Ruderfer Dm, Sang-Yun Oh, Virha Milanova, Ann Olincy, Line Olsen, Collier Da, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Schubert Cr, Elena Parkhomenko, Michele T. Pato, Cloninger Cr, Tiina Paunio, Milica Pejovic-Milovancevic, Scolnick Em, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Crowley Jj, Andrew J. Pocklington, John Powell

, Bertram Müller-Myhsok, Seidman Lj, Wellcome Trust Case-Control Consortium, Davis Kl, Eadbhard O’Callaghan, Silverman Jm, Colm O’Dushlaine, F. Anthony O’Neill, Blackwood Dhr, Smoller Jw, Stahl Ea, Psychosis Endophenotypes International Consortium, Farrell Ms, Svrakic Dm, Szatkiewicz Jp, Freimer Nb, Friedman Ji, Goldstein Ji, Wildenauer Db, Williams Nm, Hamshere Ml, Henskens Fa, Xi Hs, Hirschhorn Jn, Hollegaard Mv, Hougaard Dm, Wray Nr, Visscher Pm, Andreassen Oa, Moran Jl, Buxbaum Jd, So Hc, Welcome Trust Case-Control Consortium, Jonsson Eg, Wendland Jr, Kendler Ks, Walters Jtr, Levinson Df, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, O'Donovan Mc, Tõnu Esko

, Pablo V. Gejman, Michael Gill, Hugh Gurling, Wong Eh, Christina M. Hultman, Nakao Iwata, Mortensen Pb, Erik G. Jonsson, Assen V. Jablensky, Kenneth S. Kendler, George Kirov, Jo Knight, Nothen Mm, Todd Lencz

, Douglas F. Levinson, Erik G. Jönsson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Owen Mj, Andrew McQuillin, Jennifer L. Moran, Chen Eyh, Preben B. Mortensen, Bryan J. Mowry, Markus M. Noethen, Roel A. Ophoff, Cheung Efc, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Blackwood Dh, Tracey L. Petryshen, Markus M. Nöthen, Danielle Posthuma, Sham Pc, Weinberger Dr, Daly Mj, Sullivan Pf, Mark J. Daly, Michael C. O'Donovan, Michael C. O’Donovan

, Brendan Bulik-Sullivan, David A. Collier, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C. K. Chan, Ronald Y. L. Chen, Eric Y. H. Chen, Wei Cheng, Eric F. C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Neale Bm, Nadine Cohen, Iingrid Agartz, Siow Ann Chong, Kahler Ak, Loughland Cm, Maher Bs, McIntosh Am, Meijer Cj, Spencer Cca, Zita Ausrele Kucinskiene, Pocklington Aj, Pulver Ae, Richards Al, Sanders Ar, Fanous Ah, Webb Bt, Wolen Ar, Hartmann Am, Wormley Bk, Zai Cc, F. Anthony O’Neill, Borglum Ad, Spencer Ca, Rolf Adolfsson, Hultman Cm, Jablensky Av, Ole A. Andreassen

, Douglas H. R. Blackwood, Elvira Bramon, Anders D. Borglum, Joseph D. Buxbaum, Sven Cichon, Malhotra Ak, Anders D. Børglum, Mowry Bj, Pato Cn, Riley Bp, Psychiat Genomics Consortium, Psychosis Endophenotypes Int Conso, Wellcome Trust Case-Control Consor

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Abstract

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.

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Biological insights from 108 schizophrenia-associated genetic loci

Abstract