Genome-wide association study identifies five new schizophrenia loci

Stephan Ripke; Alan R. Sanders; Kenneth S. Kendler; Douglas F. Levinson; Pamela Sklar; Peter A. Holmans; Dan Yu Lin; Jubao Duan; Roel A. Ophoff; Ole A. Andreassen; Edward Scolnick; Sven Cichon; David St. Clair; Aiden Corvin; Hugh Gurling; Thomas Werge; Dan Rujescu; Douglas H.R. Blackwood; Carlos N. Pato; Anil K. Malhotra; Shaun Purcell; Frank Dudbridge; Benjamin M. Neale; Lizzy Rossin; Peter M. Visscher; Danielle Posthuma; Douglas M. Ruderfer; Ayman Fanous; Hreinn Stefansson; Stacy Steinberg; Bryan J. Mowry; Vera Golimbet; Marc De Hert; Erik G. Jönsson; István Bitter; Olli P.H. Pietiläinen; David A. Collier; Sarah Tosato; Ingrid Agartz; Margot Albus; Madeline Alexander; Richard L. Amdur; Farooq Amin; Nicholas Bass; Sarah E. Bergen; Donald W. Black; Anders D. Børglum; Matthew A. Brown; Richard Bruggeman; Nancy G. Buccola; William F. Byerley; Wiepke Cahn; Rita M. Cantor; Vaughan J. Carr; Stanley V. Catts; Khalid Choudhury; C. Robert Cloninger; Paul Cormican; Nicholas Craddock; Patrick A. Danoy; Susmita Datta; Lieuwe De Haan; Ditte Demontis; Dimitris Dikeos; Srdjan Djurovic; Peter Donnelly; Gary Donohoe; Linh Duong; Sarah Dwyer; Anders Fink-Jensen; Robert Freedman; Nelson B. Freimer; Marion Friedl; Lyudmila Georgieva; Ina Giegling; Michael Gill; Birte Glenthøj; Stephanie Godard; Marian Hamshere; Mark Hansen; Thomas Hansen; Annette M. Hartmann; Frans A. Henskens; David M. Hougaard; Christina M. Hultman; Andrés Ingason; Assen V. Jablensky; Klaus D. Jakobsen; Maurice Jay; Gesche Jürgens; René S. Kahn; Matthew C. Keller; Gunter Kenis; Elaine Kenny; Yunjung Kim; George K. Kirov; Heike Konnerth; Bettina Konte; Lydia Krabbendam; Robert Krasucki; Virginia K. Lasseter; Claudine Laurent; Jacob Lawrence; Todd Lencz; F. Bernard Lerer; Kung Yee Liang; Paul Lichtenstein; Jeffrey A. Lieberman; Don H. Linszen; Jouko Lönnqvist; Carmel M. Loughland; Alan W. MacLean; Brion S. Maher; Wolfgang Maier; Jacques Mallet; Pat Malloy; Manuel Mattheisen; Morten Mattingsdal; Kevin A. McGhee; John J. McGrath; Andrew McIntosh; Duncan E. McLean; Andrew McQuillin; Ingrid Melle; Patricia T. Michie; Vihra Milanova; Derek W. Morris; Ole Mors; Preben B. Mortensen; Valentina Moskvina; Pierandrea Muglia; Inez Myin-Germeys; Deborah A. Nertney; Gerald Nestadt; Jimmi Nielsen; Ivan Nikolov; Merete Nordentoft; Nadine Norton; Markus M. Nöthen; Colm T. O'Dushlaine; Ann Olincy; Line Olsen; F. Anthony O'Neill; Torben F. Ørntoft; Michael J. Owen; Christos Pantelis; George Papadimitriou; Michele T. Pato; Leena Peltonen; Hannes Petursson; Ben Pickard; Jonathan Pimm; Ann E. Pulver; Vinay Puri; Digby Quested; Emma M. Quinn; Henrik B. Rasmussen; János M. Réthelyi; Robert Ribble; Marcella Rietschel; Brien P. Riley; Mirella Ruggeri; Ulrich Schall; Thomas G. Schulze; Sibylle G. Schwab; Rodney J. Scott; Jianxin Shi; Engilbert Sigurdsson; Jeremy M. Silverman; Chris C.A. Spencer; Kari Stefansson; Amy Strange; Eric Strengman; T. Scott Stroup; Jaana Suvisaari; Lars Terenius; Srinivasa Thirumalai; Johan H. Thygesen; Sally Timm; Draga Toncheva; Edwin Van Den Oord; Jim Van Os; Ruud Van Winkel; Jan Veldink; Dermot Walsh; August G. Wang; Durk Wiersma; Dieter B. Wildenauer; Hywel J. Williams; Nigel M. Williams; Brandon Wormley; Stan Zammit; Patrick F. Sullivan; Michael C. O'Donovan; Mark J. Daly; Pablo V. Gejman

doi:10.1038/ng.940

Genome-wide association study identifies five new schizophrenia loci

Stephan Ripke, Alan R. Sanders, Kenneth S. Kendler, Douglas F. Levinson, Pamela Sklar, Peter A. Holmans, Dan Yu Lin, Jubao Duan, Roel A. Ophoff, Ole A. Andreassen, Edward Scolnick, Sven Cichon, David St. Clair, Aiden Corvin, Hugh Gurling, Thomas Werge, Dan Rujescu, Douglas H.R. Blackwood, Carlos N. Pato, Anil K. MalhotraShaun Purcell, Frank Dudbridge, Benjamin M. Neale, Lizzy Rossin, Peter M. Visscher, Danielle Posthuma, Douglas M. Ruderfer, Ayman Fanous, Hreinn Stefansson, Stacy Steinberg, Bryan J. Mowry, Vera Golimbet, Marc De Hert, Erik G. Jönsson, István Bitter, Olli P.H. Pietiläinen, David A. Collier, Sarah Tosato, Ingrid Agartz, Margot Albus, Madeline Alexander, Richard L. Amdur, Farooq Amin, Nicholas Bass, Sarah E. Bergen, Donald W. Black, Anders D. Børglum, Matthew A. Brown, Richard Bruggeman, Nancy G. Buccola, William F. Byerley, Wiepke Cahn, Rita M. Cantor, Vaughan J. Carr, Stanley V. Catts, Khalid Choudhury, C. Robert Cloninger, Paul Cormican, Nicholas Craddock, Patrick A. Danoy, Susmita Datta, Lieuwe De Haan, Ditte Demontis, Dimitris Dikeos, Srdjan Djurovic, Peter Donnelly, Gary Donohoe, Linh Duong, Sarah Dwyer, Anders Fink-Jensen, Robert Freedman, Nelson B. Freimer, Marion Friedl, Lyudmila Georgieva, Ina Giegling, Michael Gill, Birte Glenthøj, Stephanie Godard, Marian Hamshere, Mark Hansen, Thomas Hansen, Annette M. Hartmann, Frans A. Henskens, David M. Hougaard, Christina M. Hultman, Andrés Ingason, Assen V. Jablensky, Klaus D. Jakobsen, Maurice Jay, Gesche Jürgens, René S. Kahn, Matthew C. Keller, Gunter Kenis, Elaine Kenny, Yunjung Kim, George K. Kirov, Heike Konnerth, Bettina Konte, Lydia Krabbendam, Robert Krasucki, Virginia K. Lasseter, Claudine Laurent, Jacob Lawrence, Todd Lencz, F. Bernard Lerer, Kung Yee Liang, Paul Lichtenstein, Jeffrey A. Lieberman, Don H. Linszen, Jouko Lönnqvist, Carmel M. Loughland, Alan W. MacLean, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Pat Malloy, Manuel Mattheisen, Morten Mattingsdal, Kevin A. McGhee, John J. McGrath, Andrew McIntosh, Duncan E. McLean, Andrew McQuillin, Ingrid Melle, Patricia T. Michie, Vihra Milanova, Derek W. Morris, Ole Mors, Preben B. Mortensen, Valentina Moskvina, Pierandrea Muglia, Inez Myin-Germeys, Deborah A. Nertney, Gerald Nestadt, Jimmi Nielsen, Ivan Nikolov, Merete Nordentoft, Nadine Norton, Markus M. Nöthen, Colm T. O'Dushlaine, Ann Olincy, Line Olsen, F. Anthony O'Neill, Torben F. Ørntoft, Michael J. Owen, Christos Pantelis, George Papadimitriou, Michele T. Pato, Leena Peltonen, Hannes Petursson, Ben Pickard, Jonathan Pimm, Ann E. Pulver, Vinay Puri, Digby Quested, Emma M. Quinn, Henrik B. Rasmussen, János M. Réthelyi, Robert Ribble, Marcella Rietschel, Brien P. Riley, Mirella Ruggeri, Ulrich Schall, Thomas G. Schulze, Sibylle G. Schwab, Rodney J. Scott, Jianxin Shi, Engilbert Sigurdsson, Jeremy M. Silverman, Chris C.A. Spencer, Kari Stefansson, Amy Strange, Eric Strengman, T. Scott Stroup, Jaana Suvisaari, Lars Terenius, Srinivasa Thirumalai, Johan H. Thygesen, Sally Timm, Draga Toncheva, Edwin Van Den Oord, Jim Van Os, Ruud Van Winkel, Jan Veldink, Dermot Walsh, August G. Wang, Durk Wiersma, Dieter B. Wildenauer, Hywel J. Williams, Nigel M. Williams, Brandon Wormley, Stan Zammit, Patrick F. Sullivan, Michael C. O'Donovan, Mark J. Daly, Pablo V. Gejman

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Abstract

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 × 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 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

Original language	English
Pages (from-to)	969-978
Number of pages	10
Journal	Nature Genetics
Volume	43
Issue number	10
DOIs	https://doi.org/10.1038/ng.940
State	Published - Oct 2011

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10.1038/ng.940

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Ripke, S., Sanders, A. R., Kendler, K. S., Levinson, D. F., Sklar, P., Holmans, P. A., Lin, D. Y., Duan, J., Ophoff, R. A., Andreassen, O. A., Scolnick, E., Cichon, S., St. Clair, D., Corvin, A., Gurling, H., Werge, T., Rujescu, D., Blackwood, D. H. R., Pato, C. N., ... Gejman, P. V. (2011). Genome-wide association study identifies five new schizophrenia loci. Nature Genetics, 43(10), 969-978. https://doi.org/10.1038/ng.940

Ripke, Stephan ; Sanders, Alan R. ; Kendler, Kenneth S. ; Levinson, Douglas F. ; Sklar, Pamela ; Holmans, Peter A. ; Lin, Dan Yu ; Duan, Jubao ; Ophoff, Roel A. ; Andreassen, Ole A. ; Scolnick, Edward ; Cichon, Sven ; St. Clair, David ; Corvin, Aiden ; Gurling, Hugh ; Werge, Thomas ; Rujescu, Dan ; Blackwood, Douglas H.R. ; Pato, Carlos N. ; Malhotra, Anil K. ; Purcell, Shaun ; Dudbridge, Frank ; Neale, Benjamin M. ; Rossin, Lizzy ; Visscher, Peter M. ; Posthuma, Danielle ; Ruderfer, Douglas M. ; Fanous, Ayman ; Stefansson, Hreinn ; Steinberg, Stacy ; Mowry, Bryan J. ; Golimbet, Vera ; De Hert, Marc ; Jönsson, Erik G. ; Bitter, István ; Pietiläinen, Olli P.H. ; Collier, David A. ; Tosato, Sarah ; Agartz, Ingrid ; Albus, Margot ; Alexander, Madeline ; Amdur, Richard L. ; Amin, Farooq ; Bass, Nicholas ; Bergen, Sarah E. ; Black, Donald W. ; Børglum, Anders D. ; Brown, Matthew A. ; Bruggeman, Richard ; Buccola, Nancy G. ; Byerley, William F. ; Cahn, Wiepke ; Cantor, Rita M. ; Carr, Vaughan J. ; Catts, Stanley V. ; Choudhury, Khalid ; Cloninger, C. Robert ; Cormican, Paul ; Craddock, Nicholas ; Danoy, Patrick A. ; Datta, Susmita ; De Haan, Lieuwe ; Demontis, Ditte ; Dikeos, Dimitris ; Djurovic, Srdjan ; Donnelly, Peter ; Donohoe, Gary ; Duong, Linh ; Dwyer, Sarah ; Fink-Jensen, Anders ; Freedman, Robert ; Freimer, Nelson B. ; Friedl, Marion ; Georgieva, Lyudmila ; Giegling, Ina ; Gill, Michael ; Glenthøj, Birte ; Godard, Stephanie ; Hamshere, Marian ; Hansen, Mark ; Hansen, Thomas ; Hartmann, Annette M. ; Henskens, Frans A. ; Hougaard, David M. ; Hultman, Christina M. ; Ingason, Andrés ; Jablensky, Assen V. ; Jakobsen, Klaus D. ; Jay, Maurice ; Jürgens, Gesche ; Kahn, René S. ; Keller, Matthew C. ; Kenis, Gunter ; Kenny, Elaine ; Kim, Yunjung ; Kirov, George K. ; Konnerth, Heike ; Konte, Bettina ; Krabbendam, Lydia ; Krasucki, Robert ; Lasseter, Virginia K. ; Laurent, Claudine ; Lawrence, Jacob ; Lencz, Todd ; Lerer, F. Bernard ; Liang, Kung Yee ; Lichtenstein, Paul ; Lieberman, Jeffrey A. ; Linszen, Don H. ; Lönnqvist, Jouko ; Loughland, Carmel M. ; MacLean, Alan W. ; Maher, Brion S. ; Maier, Wolfgang ; Mallet, Jacques ; Malloy, Pat ; Mattheisen, Manuel ; Mattingsdal, Morten ; McGhee, Kevin A. ; McGrath, John J. ; McIntosh, Andrew ; McLean, Duncan E. ; McQuillin, Andrew ; Melle, Ingrid ; Michie, Patricia T. ; Milanova, Vihra ; Morris, Derek W. ; Mors, Ole ; Mortensen, Preben B. ; Moskvina, Valentina ; Muglia, Pierandrea ; Myin-Germeys, Inez ; Nertney, Deborah A. ; Nestadt, Gerald ; Nielsen, Jimmi ; Nikolov, Ivan ; Nordentoft, Merete ; Norton, Nadine ; Nöthen, Markus M. ; O'Dushlaine, Colm T. ; Olincy, Ann ; Olsen, Line ; O'Neill, F. Anthony ; Ørntoft, Torben F. ; Owen, Michael J. ; Pantelis, Christos ; Papadimitriou, George ; Pato, Michele T. ; Peltonen, Leena ; Petursson, Hannes ; Pickard, Ben ; Pimm, Jonathan ; Pulver, Ann E. ; Puri, Vinay ; Quested, Digby ; Quinn, Emma M. ; Rasmussen, Henrik B. ; Réthelyi, János M. ; Ribble, Robert ; Rietschel, Marcella ; Riley, Brien P. ; Ruggeri, Mirella ; Schall, Ulrich ; Schulze, Thomas G. ; Schwab, Sibylle G. ; Scott, Rodney J. ; Shi, Jianxin ; Sigurdsson, Engilbert ; Silverman, Jeremy M. ; Spencer, Chris C.A. ; Stefansson, Kari ; Strange, Amy ; Strengman, Eric ; Stroup, T. Scott ; Suvisaari, Jaana ; Terenius, Lars ; Thirumalai, Srinivasa ; Thygesen, Johan H. ; Timm, Sally ; Toncheva, Draga ; Van Den Oord, Edwin ; Van Os, Jim ; Van Winkel, Ruud ; Veldink, Jan ; Walsh, Dermot ; Wang, August G. ; Wiersma, Durk ; Wildenauer, Dieter B. ; Williams, Hywel J. ; Williams, Nigel M. ; Wormley, Brandon ; Zammit, Stan ; Sullivan, Patrick F. ; O'Donovan, Michael C. ; Daly, Mark J. ; Gejman, Pablo V. / Genome-wide association study identifies five new schizophrenia loci. In: Nature Genetics. 2011 ; Vol. 43, No. 10. pp. 969-978.

@article{341bb19a17594aa791be045e13fa62a0,

title = "Genome-wide association study identifies five new schizophrenia loci",

abstract = "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 × 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 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).",

author = "Stephan Ripke and Sanders, {Alan R.} and Kendler, {Kenneth S.} and Levinson, {Douglas F.} and Pamela Sklar and Holmans, {Peter A.} and Lin, {Dan Yu} and Jubao Duan and Ophoff, {Roel A.} and Andreassen, {Ole A.} and Edward Scolnick and Sven Cichon and {St. Clair}, David and Aiden Corvin and Hugh Gurling and Thomas Werge and Dan Rujescu and Blackwood, {Douglas H.R.} and Pato, {Carlos N.} and Malhotra, {Anil K.} and Shaun Purcell and Frank Dudbridge and Neale, {Benjamin M.} and Lizzy Rossin and Visscher, {Peter M.} and Danielle Posthuma and Ruderfer, {Douglas M.} and Ayman Fanous and Hreinn Stefansson and Stacy Steinberg and Mowry, {Bryan J.} and Vera Golimbet and {De Hert}, Marc and J{\"o}nsson, {Erik G.} and Istv{\'a}n Bitter and Pietil{\"a}inen, {Olli P.H.} and Collier, {David A.} and Sarah Tosato and Ingrid Agartz and Margot Albus and Madeline Alexander and Amdur, {Richard L.} and Farooq Amin and Nicholas Bass and Bergen, {Sarah E.} and Black, {Donald W.} and B{\o}rglum, {Anders D.} and Brown, {Matthew A.} and Richard Bruggeman and Buccola, {Nancy G.} and Byerley, {William F.} and Wiepke Cahn and Cantor, {Rita M.} and Carr, {Vaughan J.} and Catts, {Stanley V.} and Khalid Choudhury and Cloninger, {C. Robert} and Paul Cormican and Nicholas Craddock and Danoy, {Patrick A.} and Susmita Datta and {De Haan}, Lieuwe and Ditte Demontis and Dimitris Dikeos and Srdjan Djurovic and Peter Donnelly and Gary Donohoe and Linh Duong and Sarah Dwyer and Anders Fink-Jensen and Robert Freedman and Freimer, {Nelson B.} and Marion Friedl and Lyudmila Georgieva and Ina Giegling and Michael Gill and Birte Glenth{\o}j and Stephanie Godard and Marian Hamshere and Mark Hansen and Thomas Hansen and Hartmann, {Annette M.} and Henskens, {Frans A.} and Hougaard, {David M.} and Hultman, {Christina M.} and Andr{\'e}s Ingason and Jablensky, {Assen V.} and Jakobsen, {Klaus D.} and Maurice Jay and Gesche J{\"u}rgens and Kahn, {Ren{\'e} S.} and Keller, {Matthew C.} and Gunter Kenis and Elaine Kenny and Yunjung Kim and Kirov, {George K.} and Heike Konnerth and Bettina Konte and Lydia Krabbendam and Robert Krasucki and Lasseter, {Virginia K.} and Claudine Laurent and Jacob Lawrence and Todd Lencz and Lerer, {F. Bernard} and Liang, {Kung Yee} and Paul Lichtenstein and Lieberman, {Jeffrey A.} and Linszen, {Don H.} and Jouko L{\"o}nnqvist and Loughland, {Carmel M.} and MacLean, {Alan W.} and Maher, {Brion S.} and Wolfgang Maier and Jacques Mallet and Pat Malloy and Manuel Mattheisen and Morten Mattingsdal and McGhee, {Kevin A.} and McGrath, {John J.} and Andrew McIntosh and McLean, {Duncan E.} and Andrew McQuillin and Ingrid Melle and Michie, {Patricia T.} and Vihra Milanova and Morris, {Derek W.} and Ole Mors and Mortensen, {Preben B.} and Valentina Moskvina and Pierandrea Muglia and Inez Myin-Germeys and Nertney, {Deborah A.} and Gerald Nestadt and Jimmi Nielsen and Ivan Nikolov and Merete Nordentoft and Nadine Norton and N{\"o}then, {Markus M.} and O'Dushlaine, {Colm T.} and Ann Olincy and Line Olsen and O'Neill, {F. Anthony} and {\O}rntoft, {Torben F.} and Owen, {Michael J.} and Christos Pantelis and George Papadimitriou and Pato, {Michele T.} and Leena Peltonen and Hannes Petursson and Ben Pickard and Jonathan Pimm and Pulver, {Ann E.} and Vinay Puri and Digby Quested and Quinn, {Emma M.} and Rasmussen, {Henrik B.} and R{\'e}thelyi, {J{\'a}nos M.} and Robert Ribble and Marcella Rietschel and Riley, {Brien P.} and Mirella Ruggeri and Ulrich Schall and Schulze, {Thomas G.} and Schwab, {Sibylle G.} and Scott, {Rodney J.} and Jianxin Shi and Engilbert Sigurdsson and Silverman, {Jeremy M.} and Spencer, {Chris C.A.} and Kari Stefansson and Amy Strange and Eric Strengman and Stroup, {T. Scott} and Jaana Suvisaari and Lars Terenius and Srinivasa Thirumalai and Thygesen, {Johan H.} and Sally Timm and Draga Toncheva and {Van Den Oord}, Edwin and {Van Os}, Jim and {Van Winkel}, Ruud and Jan Veldink and Dermot Walsh and Wang, {August G.} and Durk Wiersma and Wildenauer, {Dieter B.} and Williams, {Hywel J.} and Williams, {Nigel M.} and Brandon Wormley and Stan Zammit and Sullivan, {Patrick F.} and O'Donovan, {Michael C.} and Daly, {Mark J.} and Gejman, {Pablo V.}",

year = "2011",

month = oct,

doi = "10.1038/ng.940",

language = "English",

volume = "43",

pages = "969--978",

journal = "Nature Genetics",

issn = "1061-4036",

number = "10",

}

Ripke, S, Sanders, AR, Kendler, KS, Levinson, DF, Sklar, P, Holmans, PA, Lin, DY, Duan, J, Ophoff, RA, Andreassen, OA, Scolnick, E, Cichon, S, St. Clair, D, Corvin, A, Gurling, H, Werge, T, Rujescu, D, Blackwood, DHR, Pato, CN, Malhotra, AK, Purcell, S, Dudbridge, F, Neale, BM, Rossin, L, Visscher, PM, Posthuma, D, Ruderfer, DM, Fanous, A, Stefansson, H, Steinberg, S, Mowry, BJ, Golimbet, V, De Hert, M, Jönsson, EG, Bitter, I, Pietiläinen, OPH, Collier, DA, Tosato, S, Agartz, I, Albus, M, Alexander, M, Amdur, RL, Amin, F, Bass, N, Bergen, SE, Black, DW, Børglum, AD, Brown, MA, Bruggeman, R, Buccola, NG, Byerley, WF, Cahn, W, Cantor, RM, Carr, VJ, Catts, SV, Choudhury, K, Cloninger, CR, Cormican, P, Craddock, N, Danoy, PA, Datta, S, De Haan, L, Demontis, D, Dikeos, D, Djurovic, S, Donnelly, P, Donohoe, G, Duong, L, Dwyer, S, Fink-Jensen, A, Freedman, R, Freimer, NB, Friedl, M, Georgieva, L, Giegling, I, Gill, M, Glenthøj, B, Godard, S, Hamshere, M, Hansen, M, Hansen, T, Hartmann, AM, Henskens, FA, Hougaard, DM, Hultman, CM, Ingason, A, Jablensky, AV, Jakobsen, KD, Jay, M, Jürgens, G, Kahn, RS, Keller, MC, Kenis, G, Kenny, E, Kim, Y, Kirov, GK, Konnerth, H, Konte, B, Krabbendam, L, Krasucki, R, Lasseter, VK, Laurent, C, Lawrence, J, Lencz, T, Lerer, FB, Liang, KY, Lichtenstein, P, Lieberman, JA, Linszen, DH, Lönnqvist, J, Loughland, CM, MacLean, AW, Maher, BS, Maier, W, Mallet, J, Malloy, P, Mattheisen, M, Mattingsdal, M, McGhee, KA, McGrath, JJ, McIntosh, A, McLean, DE, McQuillin, A, Melle, I, Michie, PT, Milanova, V, Morris, DW, Mors, O, Mortensen, PB, Moskvina, V, Muglia, P, Myin-Germeys, I, Nertney, DA, Nestadt, G, Nielsen, J, Nikolov, I, Nordentoft, M, Norton, N, Nöthen, MM, O'Dushlaine, CT, Olincy, A, Olsen, L, O'Neill, FA, Ørntoft, TF, Owen, MJ, Pantelis, C, Papadimitriou, G, Pato, MT, Peltonen, L, Petursson, H, Pickard, B, Pimm, J, Pulver, AE, Puri, V, Quested, D, Quinn, EM, Rasmussen, HB, Réthelyi, JM, Ribble, R, Rietschel, M, Riley, BP, Ruggeri, M, Schall, U, Schulze, TG, Schwab, SG, Scott, RJ, Shi, J, Sigurdsson, E, Silverman, JM, Spencer, CCA, Stefansson, K, Strange, A, Strengman, E, Stroup, TS, Suvisaari, J, Terenius, L, Thirumalai, S, Thygesen, JH, Timm, S, Toncheva, D, Van Den Oord, E, Van Os, J, Van Winkel, R, Veldink, J, Walsh, D, Wang, AG, Wiersma, D, Wildenauer, DB, Williams, HJ, Williams, NM, Wormley, B, Zammit, S, Sullivan, PF, O'Donovan, MC, Daly, MJ & Gejman, PV 2011, 'Genome-wide association study identifies five new schizophrenia loci', Nature Genetics, vol. 43, no. 10, pp. 969-978. https://doi.org/10.1038/ng.940

Genome-wide association study identifies five new schizophrenia loci. / Ripke, Stephan; Sanders, Alan R.; Kendler, Kenneth S.; Levinson, Douglas F.; Sklar, Pamela; Holmans, Peter A.; Lin, Dan Yu; Duan, Jubao; Ophoff, Roel A.; Andreassen, Ole A.; Scolnick, Edward; Cichon, Sven; St. Clair, David; Corvin, Aiden; Gurling, Hugh; Werge, Thomas; Rujescu, Dan; Blackwood, Douglas H.R.; Pato, Carlos N.; Malhotra, Anil K.; Purcell, Shaun; Dudbridge, Frank; Neale, Benjamin M.; Rossin, Lizzy; Visscher, Peter M.; Posthuma, Danielle; Ruderfer, Douglas M.; Fanous, Ayman; Stefansson, Hreinn; Steinberg, Stacy; Mowry, Bryan J.; Golimbet, Vera; De Hert, Marc; Jönsson, Erik G.; Bitter, István; Pietiläinen, Olli P.H.; Collier, David A.; Tosato, Sarah; Agartz, Ingrid; Albus, Margot; Alexander, Madeline; Amdur, Richard L.; Amin, Farooq; Bass, Nicholas; Bergen, Sarah E.; Black, Donald W.; Børglum, Anders D.; Brown, Matthew A.; Bruggeman, Richard; Buccola, Nancy G.; Byerley, William F.; Cahn, Wiepke; Cantor, Rita M.; Carr, Vaughan J.; Catts, Stanley V.; Choudhury, Khalid; Cloninger, C. Robert; Cormican, Paul; Craddock, Nicholas; Danoy, Patrick A.; Datta, Susmita; De Haan, Lieuwe; Demontis, Ditte; Dikeos, Dimitris; Djurovic, Srdjan; Donnelly, Peter; Donohoe, Gary; Duong, Linh; Dwyer, Sarah; Fink-Jensen, Anders; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Georgieva, Lyudmila; Giegling, Ina; Gill, Michael; Glenthøj, Birte; Godard, Stephanie; Hamshere, Marian; Hansen, Mark; Hansen, Thomas; Hartmann, Annette M.; Henskens, Frans A.; Hougaard, David M.; Hultman, Christina M.; Ingason, Andrés; Jablensky, Assen V.; Jakobsen, Klaus D.; Jay, Maurice; Jürgens, Gesche; Kahn, René S.; Keller, Matthew C.; Kenis, Gunter; Kenny, Elaine; Kim, Yunjung; Kirov, George K.; Konnerth, Heike; Konte, Bettina; Krabbendam, Lydia; Krasucki, Robert; Lasseter, Virginia K.; Laurent, Claudine; Lawrence, Jacob; Lencz, Todd; Lerer, F. Bernard; Liang, Kung Yee; Lichtenstein, Paul; Lieberman, Jeffrey A.; Linszen, Don H.; Lönnqvist, Jouko; Loughland, Carmel M.; MacLean, Alan W.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Malloy, Pat; Mattheisen, Manuel; Mattingsdal, Morten; McGhee, Kevin A.; McGrath, John J.; McIntosh, Andrew; McLean, Duncan E.; McQuillin, Andrew; Melle, Ingrid; Michie, Patricia T.; Milanova, Vihra; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Moskvina, Valentina; Muglia, Pierandrea; Myin-Germeys, Inez; Nertney, Deborah A.; Nestadt, Gerald; Nielsen, Jimmi; Nikolov, Ivan; Nordentoft, Merete; Norton, Nadine; Nöthen, Markus M.; O'Dushlaine, Colm T.; Olincy, Ann; Olsen, Line; O'Neill, F. Anthony; Ørntoft, Torben F.; Owen, Michael J.; Pantelis, Christos; Papadimitriou, George; Pato, Michele T.; Peltonen, Leena; Petursson, Hannes; Pickard, Ben; Pimm, Jonathan; Pulver, Ann E.; Puri, Vinay; Quested, Digby; Quinn, Emma M.; Rasmussen, Henrik B.; Réthelyi, János M.; Ribble, Robert; Rietschel, Marcella; Riley, Brien P.; Ruggeri, Mirella; Schall, Ulrich; Schulze, Thomas G.; Schwab, Sibylle G.; Scott, Rodney J.; Shi, Jianxin; Sigurdsson, Engilbert; Silverman, Jeremy M.; Spencer, Chris C.A.; Stefansson, Kari; Strange, Amy; Strengman, Eric; Stroup, T. Scott; Suvisaari, Jaana; Terenius, Lars; Thirumalai, Srinivasa; Thygesen, Johan H.; Timm, Sally; Toncheva, Draga; Van Den Oord, Edwin; Van Os, Jim; Van Winkel, Ruud; Veldink, Jan; Walsh, Dermot; Wang, August G.; Wiersma, Durk; Wildenauer, Dieter B.; Williams, Hywel J.; Williams, Nigel M.; Wormley, Brandon; Zammit, Stan; Sullivan, Patrick F.; O'Donovan, Michael C.; Daly, Mark J.; Gejman, Pablo V.

In: Nature Genetics, Vol. 43, No. 10, 10.2011, p. 969-978.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association study identifies five new schizophrenia loci

AU - Ripke, Stephan

AU - Sanders, Alan R.

AU - Kendler, Kenneth S.

AU - Levinson, Douglas F.

AU - Sklar, Pamela

AU - Holmans, Peter A.

AU - Lin, Dan Yu

AU - Duan, Jubao

AU - Ophoff, Roel A.

AU - Andreassen, Ole A.

AU - Scolnick, Edward

AU - Cichon, Sven

AU - St. Clair, David

AU - Corvin, Aiden

AU - Gurling, Hugh

AU - Werge, Thomas

AU - Rujescu, Dan

AU - Blackwood, Douglas H.R.

AU - Pato, Carlos N.

AU - Malhotra, Anil K.

AU - Purcell, Shaun

AU - Dudbridge, Frank

AU - Neale, Benjamin M.

AU - Rossin, Lizzy

AU - Visscher, Peter M.

AU - Posthuma, Danielle

AU - Ruderfer, Douglas M.

AU - Fanous, Ayman

AU - Stefansson, Hreinn

AU - Steinberg, Stacy

AU - Mowry, Bryan J.

AU - Golimbet, Vera

AU - De Hert, Marc

AU - Jönsson, Erik G.

AU - Bitter, István

AU - Pietiläinen, Olli P.H.

AU - Collier, David A.

AU - Tosato, Sarah

AU - Agartz, Ingrid

AU - Albus, Margot

AU - Alexander, Madeline

AU - Amdur, Richard L.

AU - Amin, Farooq

AU - Bass, Nicholas

AU - Bergen, Sarah E.

AU - Black, Donald W.

AU - Børglum, Anders D.

AU - Brown, Matthew A.

AU - Bruggeman, Richard

AU - Buccola, Nancy G.

AU - Byerley, William F.

AU - Cahn, Wiepke

AU - Cantor, Rita M.

AU - Carr, Vaughan J.

AU - Catts, Stanley V.

AU - Choudhury, Khalid

AU - Cloninger, C. Robert

AU - Cormican, Paul

AU - Craddock, Nicholas

AU - Danoy, Patrick A.

AU - Datta, Susmita

AU - De Haan, Lieuwe

AU - Demontis, Ditte

AU - Dikeos, Dimitris

AU - Djurovic, Srdjan

AU - Donnelly, Peter

AU - Donohoe, Gary

AU - Duong, Linh

AU - Dwyer, Sarah

AU - Fink-Jensen, Anders

AU - Freedman, Robert

AU - Freimer, Nelson B.

AU - Friedl, Marion

AU - Georgieva, Lyudmila

AU - Giegling, Ina

AU - Gill, Michael

AU - Glenthøj, Birte

AU - Godard, Stephanie

AU - Hamshere, Marian

AU - Hansen, Mark

AU - Hansen, Thomas

AU - Hartmann, Annette M.

AU - Henskens, Frans A.

AU - Hougaard, David M.

AU - Hultman, Christina M.

AU - Ingason, Andrés

AU - Jablensky, Assen V.

AU - Jakobsen, Klaus D.

AU - Jay, Maurice

AU - Jürgens, Gesche

AU - Kahn, René S.

AU - Keller, Matthew C.

AU - Kenis, Gunter

AU - Kenny, Elaine

AU - Kim, Yunjung

AU - Kirov, George K.

AU - Konnerth, Heike

AU - Konte, Bettina

AU - Krabbendam, Lydia

AU - Krasucki, Robert

AU - Lasseter, Virginia K.

AU - Laurent, Claudine

AU - Lawrence, Jacob

AU - Lencz, Todd

AU - Lerer, F. Bernard

AU - Liang, Kung Yee

AU - Lichtenstein, Paul

AU - Lieberman, Jeffrey A.

AU - Linszen, Don H.

AU - Lönnqvist, Jouko

AU - Loughland, Carmel M.

AU - MacLean, Alan W.

AU - Maher, Brion S.

AU - Maier, Wolfgang

AU - Mallet, Jacques

AU - Malloy, Pat

AU - Mattheisen, Manuel

AU - Mattingsdal, Morten

AU - McGhee, Kevin A.

AU - McGrath, John J.

AU - McIntosh, Andrew

AU - McLean, Duncan E.

AU - McQuillin, Andrew

AU - Melle, Ingrid

AU - Michie, Patricia T.

AU - Milanova, Vihra

AU - Morris, Derek W.

AU - Mors, Ole

AU - Mortensen, Preben B.

AU - Moskvina, Valentina

AU - Muglia, Pierandrea

AU - Myin-Germeys, Inez

AU - Nertney, Deborah A.

AU - Nestadt, Gerald

AU - Nielsen, Jimmi

AU - Nikolov, Ivan

AU - Nordentoft, Merete

AU - Norton, Nadine

AU - Nöthen, Markus M.

AU - O'Dushlaine, Colm T.

AU - Olincy, Ann

AU - Olsen, Line

AU - O'Neill, F. Anthony

AU - Ørntoft, Torben F.

AU - Owen, Michael J.

AU - Pantelis, Christos

AU - Papadimitriou, George

AU - Pato, Michele T.

AU - Peltonen, Leena

AU - Petursson, Hannes

AU - Pickard, Ben

AU - Pimm, Jonathan

AU - Pulver, Ann E.

AU - Puri, Vinay

AU - Quested, Digby

AU - Quinn, Emma M.

AU - Rasmussen, Henrik B.

AU - Réthelyi, János M.

AU - Ribble, Robert

AU - Rietschel, Marcella

AU - Riley, Brien P.

AU - Ruggeri, Mirella

AU - Schall, Ulrich

AU - Schulze, Thomas G.

AU - Schwab, Sibylle G.

AU - Scott, Rodney J.

AU - Shi, Jianxin

AU - Sigurdsson, Engilbert

AU - Silverman, Jeremy M.

AU - Spencer, Chris C.A.

AU - Stefansson, Kari

AU - Strange, Amy

AU - Strengman, Eric

AU - Stroup, T. Scott

AU - Suvisaari, Jaana

AU - Terenius, Lars

AU - Thirumalai, Srinivasa

AU - Thygesen, Johan H.

AU - Timm, Sally

AU - Toncheva, Draga

AU - Van Den Oord, Edwin

AU - Van Os, Jim

AU - Van Winkel, Ruud

AU - Veldink, Jan

AU - Walsh, Dermot

AU - Wang, August G.

AU - Wiersma, Durk

AU - Wildenauer, Dieter B.

AU - Williams, Hywel J.

AU - Williams, Nigel M.

AU - Wormley, Brandon

AU - Zammit, Stan

AU - Sullivan, Patrick F.

AU - O'Donovan, Michael C.

AU - Daly, Mark J.

AU - Gejman, Pablo V.

PY - 2011/10

Y1 - 2011/10

N2 - 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 × 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 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

AB - 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 × 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 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

UR - http://www.scopus.com/inward/record.url?scp=80053384370&partnerID=8YFLogxK

U2 - 10.1038/ng.940

DO - 10.1038/ng.940

M3 - Article

C2 - 21926974

AN - SCOPUS:80053384370

VL - 43

SP - 969

EP - 978

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 10

ER -

Genome-wide association study identifies five new schizophrenia loci

Abstract

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