Genome-wide association study identifies five new schizophrenia loci

Autoria(s): Ripke, S.; Sklar, P.; Rossin, L.; Ruderfer, D.M.; Bergen, S.E.; Daly, M.J.; Sanders, A.R.; Duan, J.; Gejman, P.V.; Kendler, K.S.; Maher, B.S.; Ribble, R.; Riley, B.P.; Wormley, B.; Fanous, A.; Levinson, D.F.; Alexander, M.; Silverman, J.M.; Holmans, P.A.; Craddock, N.; Dwyer, S.; Georgieva, L.; Hamshere, M.; Kirov, G.K.; Moskvina, V.; Nikolov, I.; Norton, N.; Owen, M.J.; Williams, H.J.; Williams, N.M.; Zammit, S.; O'Donovan, M.C.; Lin, D.-Y.; Ophoff, R.A.; Strengman, E.; Cantor, R.M.; Freimer, N.B.; Andreassen, O.A.; Agartz, I.; Djurovic, S.; Mattingsdal, M.; Melle, I.; Scolnick, E.; Purcell, S.; Neale, B.M.; Cichon, S.; Mattheisen, M.; Nöthen, M.M.; St. Clair, D.; Corvin, A.; Cormican, P.; Donohoe, G.; Gill, M.; Kenny, E.; Morris, D.W.; O'Dushlaine, C.T.; Quinn, E.M.; Gurling, H.; Bass, N.; Choudhury, K.; Datta, S.; Krasucki, R.; Lawrence, J.; McQuillin, A.; Pimm, J.; Puri, V.; Werge, T.; Duong, L.; Hansen, T.; Ingason, A.; Jakobsen, K.D.; Olsen, L.; Rasmussen, H.B.; Thygesen, J.H.; Rujescu, D.; Friedl, M.; Giegling, I.; Hartmann, A.M.; Konnerth, H.; Konte, B.; Blackwood, D.H.R.; MacLean, A.W.; Malloy, P.; McGhee, K.A.; McIntosh, A.; Pato, C.N.; Pato, M.T.; Malhotra, A.K.; Lencz, T.; Dudbridge, F.; Visscher, P.M.; Posthuma, D.; Amdur, R.L.; Stefansson, H.; Steinberg, S.; Stefansson, K.; Mowry, B.J.; McGrath, J.J.; Nertney, D.A.; Golimbet, V.; De Hert, M.; Van Winkel, R.; Jönsson, E.G.; Terenius, L.; Bitter, I.; Réthelyi, J.M.; Pietiläinen, O.P.H.; Peltonen, L.; Collier, D.A.; Tosato, S.; Ruggeri, M.; Albus, M.; Amin, F.; Black, D.W.; Børglum, A.D.; Demontis, D.; Mors, O.; Brown, M.A.; Danoy, P.A.; Bruggeman, R.; Wiersma, D.; Buccola, N.G.; Byerley, W.F.; Cahn, W.; Kahn, R.S.; Carr, V.J.; Catts, S.V.; Cloninger, C.R.; De Haan, L.; Linszen, D.H.; Dikeos, D.; Papadimitriou, G.; Donnelly, P.; Spencer, C.C.A.; Strange, A.; Fink-Jensen, A.; Freedman, R.; Olincy, A.; Glenthøj, B.; Godard, S.; Hansen, M.; Henskens, F.A.; Hougaard, D.M.; Hultman, C.M.; Lichtenstein, P.; Sullivan, P.F.; Jablensky, A.V.; Jay, M.; Laurent, C.; Jürgens, G.; Keller, M.C.; Kenis, G.; Kim, Y.; Krabbendam, L.; Myin-Germeys, I.; Van Os, J.; Lasseter, V.K.; Nestadt, G.; Pulver, A.E.; Lerer, F.B.; Liang, K.-Y.; Lieberman, J.A.; Stroup, T.S.; Lönnqvist, J.; Suvisaari, J.; Loughland, C.M.; Maier, W.; Rietschel, M.; Mallet, J.; McLean, D.E.; Michie, P.T.; Schall, U.; Milanova, V.; Mortensen, P.B.; Muglia, P.; Nielsen, J.; Nordentoft, M.; O'Neill, F.A.; Ørntoft, T.F.; Pantelis, C.; Petursson, H.; Sigurdsson, E.; Pickard, B.; Quested, D.; Schulze, T.G.; Schwab, S.G.; Wildenauer, D.B.; Scott, R.J.; Shi, J.; Thirumalai, S.; Timm, S.; Toncheva, D.; Van Den Oord, E.; Veldink, J.; Walsh, D.; Wang, A.G.
Data(s)

01/10/2011
Resumo

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).
Identificador

http://pure.qub.ac.uk/portal/en/publications/genomewide-association-study-identifies-five-new-schizophrenia-loci(eb2866c5-f2be-41a2-939a-c34d799ad1db).html

http://dx.doi.org/10.1038/ng.940

http://www.scopus.com/inward/record.url?partnerID=yv4JPVwI&eid=2-s2.0-80053384370&md5=6fb1cad1cc387567b068202263888e27
Idioma(s)

eng
Direitos

info:eu-repo/semantics/restrictedAccess
Fonte

Ripke , S , Sklar , P , Rossin , L , Ruderfer , D M , Bergen , S E , Daly , M J , Sanders , A R , Duan , J , Gejman , P V , Kendler , K S , Maher , B S , Ribble , R , Riley , B P , Wormley , B , Fanous , A , Levinson , D F , Alexander , M , Silverman , J M , Holmans , P A , Craddock , N , Dwyer , S , Georgieva , L , Hamshere , M , Kirov , G K , Moskvina , V , Nikolov , I , Norton , N , Owen , M J , Williams , H J , Williams , N M , Zammit , S , O'Donovan , M C , Lin , D-Y , Ophoff , R A , Strengman , E , Cantor , R M , Freimer , N B , Andreassen , O A , Agartz , I , Djurovic , S , Mattingsdal , M , Melle , I , Scolnick , E , Purcell , S , Neale , B M , Cichon , S , Mattheisen , M , Nöthen , M M , St. Clair , D , Corvin , A , Cormican , P , Donohoe , G , Gill , M , Kenny , E , Morris , D W , O'Dushlaine , C T , Quinn , E M , Gurling , H , Bass , N , Choudhury , K , Datta , S , Krasucki , R , Lawrence , J , McQuillin , A , Pimm , J , Puri , V , Werge , T , Duong , L , Hansen , T , Ingason , A , Jakobsen , K D , Olsen , L , Rasmussen , H B , Thygesen , J H , Rujescu , D , Friedl , M , Giegling , I , Hartmann , A M , Konnerth , H , Konte , B , Blackwood , D H R , MacLean , A W , Malloy , P , McGhee , K A , McIntosh , A , Pato , C N , Pato , M T , Malhotra , A K , Lencz , T , Dudbridge , F , Visscher , P M , Posthuma , D , Amdur , R L , Stefansson , H , Steinberg , S , Stefansson , K , Mowry , B J , McGrath , J J , Nertney , D A , Golimbet , V , De Hert , M , Van Winkel , R , Jönsson , E G , Terenius , L , Bitter , I , Réthelyi , J M , Pietiläinen , O P H , Peltonen , L , Collier , D A , Tosato , S , Ruggeri , M , Albus , M , Amin , F , Black , D W , Børglum , A D , Demontis , D , Mors , O , Brown , M A , Danoy , P A , Bruggeman , R , Wiersma , D , Buccola , N G , Byerley , W F , Cahn , W , Kahn , R S , Carr , V J , Catts , S V , Cloninger , C R , De Haan , L , Linszen , D H , Dikeos , D , Papadimitriou , G , Donnelly , P , Spencer , C C A , Strange , A , Fink-Jensen , A , Freedman , R , Olincy , A , Glenthøj , B , Godard , S , Hansen , M , Henskens , F A , Hougaard , D M , Hultman , C M , Lichtenstein , P , Sullivan , P F , Jablensky , A V , Jay , M , Laurent , C , Jürgens , G , Keller , M C , Kenis , G , Kim , Y , Krabbendam , L , Myin-Germeys , I , Van Os , J , Lasseter , V K , Nestadt , G , Pulver , A E , Lerer , F B , Liang , K-Y , Lieberman , J A , Stroup , T S , Lönnqvist , J , Suvisaari , J , Loughland , C M , Maier , W , Rietschel , M , Mallet , J , McLean , D E , Michie , P T , Schall , U , Milanova , V , Mortensen , P B , Muglia , P , Nielsen , J , Nordentoft , M , O'Neill , F A , Ørntoft , T F , Pantelis , C , Petursson , H , Sigurdsson , E , Pickard , B , Quested , D , Schulze , T G , Schwab , S G , Wildenauer , D B , Scott , R J , Shi , J , Thirumalai , S , Timm , S , Toncheva , D , Van Den Oord , E , Veldink , J , Walsh , D & Wang , A G 2011 , ' Genome-wide association study identifies five new schizophrenia loci ' Nature Genetics , vol 43 , no. 10 , pp. 969-976 . DOI: 10.1038/ng.940
Palavras-Chave #/dk/atira/pure/subjectarea/asjc/1300/1311 #Genetics
Tipo

article
Acesso ao item digital