Biological insights from 108 schizophrenia-associated genetic loci

Ripke S; Neale BM; Corvin A; Walters JTR; Farh KH; Holmans PA; Lee P; Bulik-Sullivan B; Collier DA; Huang HL; Pers TH; Agartz I; Agerbo E; Albus M; Alexander M; Amin F; Bacanu SA; Begemann M; Belliveau RA; Bene J; Bergen SE; Bevilacqua E; Bigdeli TB; Black DW; Bruggeman R; Buccola NG; Buckner RL; Byerley W; Cahn W; Cai GQ; Campion D; Cantor RM; Carr VJ; Carrera N; Catts SV; Chambert KD; Chan RCK; Chen RYL; Chen EYH; Cheng W; Cheung EFC; Chong SA; Cloninger CR; Cohen D; Cohen N; Cormican P; Craddock N; Crowley JJ; Curtis D; Davidson M; Davis KL; Degenhardt F; Del Favero J; Demontis D; Dikeos D; Dinan T; Djurovic S; Donohoe G; Drapeau E; Duan J; Dudbridge F; Durmishi N; Eichhammer P; Eriksson J; Escott-Price V; Essioux L; Fanous AH; Farrell MS; Frank J; Franke L; Freedman R; Freimer NB; Friedl M; Friedman JI; Fromer M; Genovese G; Georgieva L; Giegling I; Giusti-Rodriguez P; Godard S; Goldstein JI; Golimbet V; Gopal S; Gratten J; de Haan L; Hammer C; Hamshere ML; Hansen M; Hansen T; Haroutunian V; Hartmann AM; Henskens FA; Herms S; Hirschhorn JN; Hoffmann P; Hofman A; Hollegaard MV; Hougaard DM; Ikeda M; Joa I; Julia A; Kahn RS; Kalaydjieva L; Karachanak-Yankova S; Karjalainen J; Kavanagh D; Keller MC; Kennedy JL; Khrunin A; Kim Y; Klovins J; Knowles JA; Konte B; Kucinskas V; Kucinskiene ZA; Kuzelova-Ptackova H; Kahler AK; Laurent C; Keong JLC; Lee SH; Legge SE; Lerer B; Li MX; Li T; Liang KY; Lieberman J; Limborska S; Loughland CM; Lubinski J; Lonnqvist J; Macek M; Magnusson PKE; Maher BS; Maier W; Mallet J; Marsal S; Mattheisen M; Mattingsdal M; McCarley RW; McDonald C; McIntosh AM; Meier S; Meijer CJ; Melegh B; Melle I; Mesholam-Gately RI; Metspalu A; Michie PT; Milani L; Milanova V; Mokrab Y; Morris DW; Mors O; Murphy KC; Murray RM; Myin-Germeys I; Muller-Myhsok B; Nelis M; Nenadic I; Nertney DA; Nestadt G; Nicodemus KK; Nikitina-Zake L; Nisenbaum L; Nordin A; O'Callaghan E; O'Dushlaine C; O'Neill FA; Oh SY; Olincy A; Olsen L; Van Os J; Pantelis C; Papadimitriou GN; Papiol S; Parkhomenko E; Pato MT; Paunio T; Pejovic-Milovancevic M; Perkins DO; Pietilainen O; Pimm J; Pocklington AJ; Powell J; Price A; Pulver AE; Purcell SM; Quested D; Rasmussen HB; Reichenberg A; Reimers MA; Richards AL; Roffman JL; Roussos P; Ruderfer DM; Salomaa V; Sanders AR; Schall U; Schubert CR; Schulze TG; Schwab SG; Scolnick EM; Scott RJ; Seidman LJ; Shi JX; Sigurdsson E; Silagadze T; Silverman JM; Sim K; Slominsky P; Smoller JW; So HC; Spencer CCA; Stahl EA; Stefansson H; Steinberg S; Stogmann E; Straub RE; Strengman E; Strohmaier J; Stroup TS; Subramaniam M; Suvisaari J; Svrakic DM; Szatkiewicz JP; Soderman E; Thirumalai S; Toncheva D; Tosato S; Veijola J; Waddington J; Walsh D; Wang D; Wang Q; Webb BT; Weiser M; Wildenauer DB; Williams NM; Williams S; Witt SH; Wolen AR; Wong EHM; Wormley BK; Xi HS; Zai CC; Zheng XB; Zimprich F; Wray NR; Stefansson K; Visscher PM; Adolfsson R; Andreassen OA; Blackwood DHR; Bramon E; Buxbaum JD; Borglum AD; Cichon S; Darvasi A; Domenici E; Ehrenreich H; Esko T; Gejman PV; Gill M; Gurling H; Hultman CM; Iwata N; Jablensky AV; Jonsson EG; Kendler KS; Kirov G; Knight J; Lencz T; Levinson DF; Li QQS; Liu JJ; Malhotra AK; McCarroll SA; McQuillin A; Moran JL; Mortensen PB; Mowry BJ; Nothen MM; Ophoff RA; Owen MJ; Palotie A; Pato CN; Petryshen TL; Posthuma D; Rietschel M; Riley BP; Rujescu D; Sham PC; Sklar P; St Clair D; Weinberger DR; Wendland JR; Werge T; Daly MJ; Sullivan PF; O'Donovan MC

Nature, Vol.511, No.7510, 421-421, 2014

Ripke S, Neale BM, Corvin A, Walters JTR, Farh KH, Holmans PA, Lee P, Bulik-Sullivan B, Collier DA, Huang HL, Pers TH, Agartz I, Agerbo E, Albus M, Alexander M, Amin F, Bacanu SA, Begemann M, Belliveau RA, Bene J, Bergen SE, Bevilacqua E, Bigdeli TB, Black DW, Bruggeman R, Buccola NG, Buckner RL, Byerley W, Cahn W, Cai GQ, Campion D, Cantor RM, Carr VJ, Carrera N, Catts SV, Chambert KD, Chan RCK, Chen RYL, Chen EYH, Cheng W, Cheung EFC, Chong SA, Cloninger CR, Cohen D, Cohen N, Cormican P, Craddock N, Crowley JJ, Curtis D, Davidson M, Davis KL, Degenhardt F, Del Favero J, Demontis D, Dikeos D, Dinan T, Djurovic S, Donohoe G, Drapeau E, Duan J, Dudbridge F, Durmishi N, Eichhammer P, Eriksson J, Escott-Price V, Essioux L, Fanous AH, Farrell MS, Frank J, Franke L, Freedman R, Freimer NB, Friedl M, Friedman JI, Fromer M, Genovese G, Georgieva L, Giegling I, Giusti-Rodriguez P, Godard S, Goldstein JI, Golimbet V, Gopal S, Gratten J, de Haan L, Hammer C, Hamshere ML, Hansen M, Hansen T, Haroutunian V, Hartmann AM, Henskens FA, Herms S, Hirschhorn JN, Hoffmann P, Hofman A, Hollegaard MV, Hougaard DM, Ikeda M, Joa I, Julia A, Kahn RS, Kalaydjieva L, Karachanak-Yankova S, Karjalainen J, Kavanagh D, Keller MC, Kennedy JL, Khrunin A, Kim Y, Klovins J, Knowles JA, Konte B, Kucinskas V, Kucinskiene ZA, Kuzelova-Ptackova H, Kahler AK, Laurent C, Keong JLC, Lee SH, Legge SE, Lerer B, Li MX, Li T, Liang KY, Lieberman J, Limborska S, Loughland CM, Lubinski J, Lonnqvist J, Macek M, Magnusson PKE, Maher BS, Maier W, Mallet J, Marsal S, Mattheisen M, Mattingsdal M, McCarley RW, McDonald C, McIntosh AM, Meier S, Meijer CJ, Melegh B, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mokrab Y, Morris DW, Mors O, Murphy KC, Murray RM, Myin-Germeys I, Muller-Myhsok B, Nelis M, Nenadic I, Nertney DA, Nestadt G, Nicodemus KK, Nikitina-Zake L, Nisenbaum L, Nordin A, O'Callaghan E, O'Dushlaine C, O'Neill FA, Oh SY, Olincy A, Olsen L, Van Os J, Pantelis C, Papadimitriou GN, Papiol S, Parkhomenko E, Pato MT, Paunio T, Pejovic-Milovancevic M, Perkins DO, Pietilainen O, Pimm J, Pocklington AJ, Powell J, Price A, Pulver AE, Purcell SM, Quested D, Rasmussen HB, Reichenberg A, Reimers MA, Richards AL, Roffman JL, Roussos P, Ruderfer DM, Salomaa V, Sanders AR, Schall U, Schubert CR, Schulze TG, Schwab SG, Scolnick EM, Scott RJ, Seidman LJ, Shi JX, Sigurdsson E, Silagadze T, Silverman JM, Sim K, Slominsky P, Smoller JW, So HC, Spencer CCA, Stahl EA, Stefansson H, Steinberg S, Stogmann E, Straub RE, Strengman E, Strohmaier J, Stroup TS, Subramaniam M, Suvisaari J, Svrakic DM, Szatkiewicz JP, Soderman E, Thirumalai S, Toncheva D, Tosato S, Veijola J, Waddington J, Walsh D, Wang D, Wang Q, Webb BT, Weiser M, Wildenauer DB, Williams NM, Williams S, Witt SH, Wolen AR, Wong EHM, Wormley BK, Xi HS, Zai CC, Zheng XB, Zimprich F, Wray NR, Stefansson K, Visscher PM, Adolfsson R, Andreassen OA, Blackwood DHR, Bramon E, Buxbaum JD, Borglum AD, Cichon S, Darvasi A, Domenici E, Ehrenreich H, Esko T, Gejman PV, Gill M, Gurling H, Hultman CM, Iwata N, Jablensky AV, Jonsson EG, Kendler KS, Kirov G, Knight J, Lencz T, Levinson DF, Li QQS, Liu JJ, Malhotra AK, McCarroll SA, McQuillin A, Moran JL, Mortensen PB, Mowry BJ, Nothen MM, Ophoff RA, Owen MJ, Palotie A, Pato CN, Petryshen TL, Posthuma D, Rietschel M, Riley BP, Rujescu D, Sham PC, Sklar P, St Clair D, Weinberger DR, Wendland JR, Werge T, Daly MJ, Sullivan PF, O'Donovan MC

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.