Common variant at 16p11.2 conferring risk of psychosis

S. Steinberg, S. De Jong, M. Mattheisen, J. Costas, D. Demontis, S. Jamain, O. P H Pietiläinen, K. Lin, S. Papiol, J. Huttenlocher, E. Sigurdsson, E. Vassos, I. Giegling, R. Breuer, G. Fraser, N. Walker, I. Melle, S. Djurovic, I. Agartz, A. Tuulio-HenrikssonJ. Suvisaari, J. Lönnqvist, T. Paunio, L. Olsen, T. Hansen, A. Ingason, M. Pirinen, E. Strengman, D. M. Hougaard, T. Orntoft, M. Didriksen, M. V. Hollegaard, M. Nordentoft, L. Abramova, V. Kaleda, M. Arrojo, J. Sanjuán, C. Arango, B. Etain, F. Bellivier, A. Méary, F. Schürhoff, A. Szoke, M. Ribolsi, V. Magni, A. Siracusano, S. Sperling, M. Rossner, C. Christiansen, L. A. Kiemeney, B. Franke, L. H. Van Den Berg, J. Veldink, S. Curran, P. Bolton, M. Poot, W. Staal, K. Rehnstrom, H. Kilpinen, C. M. Freitag, J. Meyer, P. Magnusson, E. Saemundsen, I. Martsenkovsky, I. Bikshaieva, I. Martsenkovska, O. Vashchenko, M. Raleva, K. Paketchieva, B. Stefanovski, N. Durmishi, M. Pejovic Milovancevic, D. Lecic Tosevski, T. Silagadze, N. Naneishvili, N. Mikeladze, S. Surguladze, J. B. Vincent, A. Farmer, P. B. Mitchell, A. Wright, P. R. Schofield, J. M. Fullerton, G. W. Montgomery, N. G. Martin, I. A. Rubino, R. Van Winkel, G. Kenis, M. De Hert, J. M. Réthelyi, I. Bitter, L. Terenius, E. G. Jönsson, S. Bakker, J. Van Os, A. Jablensky, M. Leboyer, E. Bramon, J. Powell, R. Murray, A. Corvin, M. Gill, D. Morris, F. A. O'Neill, K. Kendler, B. Riley, N. Craddock, M. J. Owen, M. C. O'Donovan, U. Thorsteinsdottir, A. Kong, H. Ehrenreich, A. Carracedo, V. Golimbet, O. A. Andreassen, A. D. Børglum, O. Mors, P. B. Mortensen, T. Werge, R. A. Ophoff, M. M. Nöthen, M. Rietschel, S. Cichon, M. Ruggeri, S. Tosato, A. Palotie, D. St Clair, D. Rujescu, D. A. Collier, H. Stefansson, K. Stefansson

Research output: Contribution to journalArticle

Abstract

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255T; odds ratio=1.08; P=6.6 × 10 -11). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255T is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Original languageEnglish
Pages (from-to)108-114
Number of pages7
JournalMolecular Psychiatry
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Psychotic Disorders
Schizophrenia
Bipolar Disorder
Body Mass Index
Genome
Genome-Wide Association Study
Meta-Analysis
Odds Ratio
Phenotype

Keywords

  • 16p11.2
  • association
  • bipolar disorder
  • cross-disorder
  • schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Steinberg, S., De Jong, S., Mattheisen, M., Costas, J., Demontis, D., Jamain, S., ... Stefansson, K. (2014). Common variant at 16p11.2 conferring risk of psychosis. Molecular Psychiatry, 19(1), 108-114. https://doi.org/10.1038/mp.2012.157

Common variant at 16p11.2 conferring risk of psychosis. / Steinberg, S.; De Jong, S.; Mattheisen, M.; Costas, J.; Demontis, D.; Jamain, S.; Pietiläinen, O. P H; Lin, K.; Papiol, S.; Huttenlocher, J.; Sigurdsson, E.; Vassos, E.; Giegling, I.; Breuer, R.; Fraser, G.; Walker, N.; Melle, I.; Djurovic, S.; Agartz, I.; Tuulio-Henriksson, A.; Suvisaari, J.; Lönnqvist, J.; Paunio, T.; Olsen, L.; Hansen, T.; Ingason, A.; Pirinen, M.; Strengman, E.; Hougaard, D. M.; Orntoft, T.; Didriksen, M.; Hollegaard, M. V.; Nordentoft, M.; Abramova, L.; Kaleda, V.; Arrojo, M.; Sanjuán, J.; Arango, C.; Etain, B.; Bellivier, F.; Méary, A.; Schürhoff, F.; Szoke, A.; Ribolsi, M.; Magni, V.; Siracusano, A.; Sperling, S.; Rossner, M.; Christiansen, C.; Kiemeney, L. A.; Franke, B.; Van Den Berg, L. H.; Veldink, J.; Curran, S.; Bolton, P.; Poot, M.; Staal, W.; Rehnstrom, K.; Kilpinen, H.; Freitag, C. M.; Meyer, J.; Magnusson, P.; Saemundsen, E.; Martsenkovsky, I.; Bikshaieva, I.; Martsenkovska, I.; Vashchenko, O.; Raleva, M.; Paketchieva, K.; Stefanovski, B.; Durmishi, N.; Pejovic Milovancevic, M.; Lecic Tosevski, D.; Silagadze, T.; Naneishvili, N.; Mikeladze, N.; Surguladze, S.; Vincent, J. B.; Farmer, A.; Mitchell, P. B.; Wright, A.; Schofield, P. R.; Fullerton, J. M.; Montgomery, G. W.; Martin, N. G.; Rubino, I. A.; Van Winkel, R.; Kenis, G.; De Hert, M.; Réthelyi, J. M.; Bitter, I.; Terenius, L.; Jönsson, E. G.; Bakker, S.; Van Os, J.; Jablensky, A.; Leboyer, M.; Bramon, E.; Powell, J.; Murray, R.; Corvin, A.; Gill, M.; Morris, D.; O'Neill, F. A.; Kendler, K.; Riley, B.; Craddock, N.; Owen, M. J.; O'Donovan, M. C.; Thorsteinsdottir, U.; Kong, A.; Ehrenreich, H.; Carracedo, A.; Golimbet, V.; Andreassen, O. A.; Børglum, A. D.; Mors, O.; Mortensen, P. B.; Werge, T.; Ophoff, R. A.; Nöthen, M. M.; Rietschel, M.; Cichon, S.; Ruggeri, M.; Tosato, S.; Palotie, A.; St Clair, D.; Rujescu, D.; Collier, D. A.; Stefansson, H.; Stefansson, K.

In: Molecular Psychiatry, Vol. 19, No. 1, 01.2014, p. 108-114.

Research output: Contribution to journalArticle

Steinberg, S, De Jong, S, Mattheisen, M, Costas, J, Demontis, D, Jamain, S, Pietiläinen, OPH, Lin, K, Papiol, S, Huttenlocher, J, Sigurdsson, E, Vassos, E, Giegling, I, Breuer, R, Fraser, G, Walker, N, Melle, I, Djurovic, S, Agartz, I, Tuulio-Henriksson, A, Suvisaari, J, Lönnqvist, J, Paunio, T, Olsen, L, Hansen, T, Ingason, A, Pirinen, M, Strengman, E, Hougaard, DM, Orntoft, T, Didriksen, M, Hollegaard, MV, Nordentoft, M, Abramova, L, Kaleda, V, Arrojo, M, Sanjuán, J, Arango, C, Etain, B, Bellivier, F, Méary, A, Schürhoff, F, Szoke, A, Ribolsi, M, Magni, V, Siracusano, A, Sperling, S, Rossner, M, Christiansen, C, Kiemeney, LA, Franke, B, Van Den Berg, LH, Veldink, J, Curran, S, Bolton, P, Poot, M, Staal, W, Rehnstrom, K, Kilpinen, H, Freitag, CM, Meyer, J, Magnusson, P, Saemundsen, E, Martsenkovsky, I, Bikshaieva, I, Martsenkovska, I, Vashchenko, O, Raleva, M, Paketchieva, K, Stefanovski, B, Durmishi, N, Pejovic Milovancevic, M, Lecic Tosevski, D, Silagadze, T, Naneishvili, N, Mikeladze, N, Surguladze, S, Vincent, JB, Farmer, A, Mitchell, PB, Wright, A, Schofield, PR, Fullerton, JM, Montgomery, GW, Martin, NG, Rubino, IA, Van Winkel, R, Kenis, G, De Hert, M, Réthelyi, JM, Bitter, I, Terenius, L, Jönsson, EG, Bakker, S, Van Os, J, Jablensky, A, Leboyer, M, Bramon, E, Powell, J, Murray, R, Corvin, A, Gill, M, Morris, D, O'Neill, FA, Kendler, K, Riley, B, Craddock, N, Owen, MJ, O'Donovan, MC, Thorsteinsdottir, U, Kong, A, Ehrenreich, H, Carracedo, A, Golimbet, V, Andreassen, OA, Børglum, AD, Mors, O, Mortensen, PB, Werge, T, Ophoff, RA, Nöthen, MM, Rietschel, M, Cichon, S, Ruggeri, M, Tosato, S, Palotie, A, St Clair, D, Rujescu, D, Collier, DA, Stefansson, H & Stefansson, K 2014, 'Common variant at 16p11.2 conferring risk of psychosis', Molecular Psychiatry, vol. 19, no. 1, pp. 108-114. https://doi.org/10.1038/mp.2012.157
Steinberg S, De Jong S, Mattheisen M, Costas J, Demontis D, Jamain S et al. Common variant at 16p11.2 conferring risk of psychosis. Molecular Psychiatry. 2014 Jan;19(1):108-114. https://doi.org/10.1038/mp.2012.157
Steinberg, S. ; De Jong, S. ; Mattheisen, M. ; Costas, J. ; Demontis, D. ; Jamain, S. ; Pietiläinen, O. P H ; Lin, K. ; Papiol, S. ; Huttenlocher, J. ; Sigurdsson, E. ; Vassos, E. ; Giegling, I. ; Breuer, R. ; Fraser, G. ; Walker, N. ; Melle, I. ; Djurovic, S. ; Agartz, I. ; Tuulio-Henriksson, A. ; Suvisaari, J. ; Lönnqvist, J. ; Paunio, T. ; Olsen, L. ; Hansen, T. ; Ingason, A. ; Pirinen, M. ; Strengman, E. ; Hougaard, D. M. ; Orntoft, T. ; Didriksen, M. ; Hollegaard, M. V. ; Nordentoft, M. ; Abramova, L. ; Kaleda, V. ; Arrojo, M. ; Sanjuán, J. ; Arango, C. ; Etain, B. ; Bellivier, F. ; Méary, A. ; Schürhoff, F. ; Szoke, A. ; Ribolsi, M. ; Magni, V. ; Siracusano, A. ; Sperling, S. ; Rossner, M. ; Christiansen, C. ; Kiemeney, L. A. ; Franke, B. ; Van Den Berg, L. H. ; Veldink, J. ; Curran, S. ; Bolton, P. ; Poot, M. ; Staal, W. ; Rehnstrom, K. ; Kilpinen, H. ; Freitag, C. M. ; Meyer, J. ; Magnusson, P. ; Saemundsen, E. ; Martsenkovsky, I. ; Bikshaieva, I. ; Martsenkovska, I. ; Vashchenko, O. ; Raleva, M. ; Paketchieva, K. ; Stefanovski, B. ; Durmishi, N. ; Pejovic Milovancevic, M. ; Lecic Tosevski, D. ; Silagadze, T. ; Naneishvili, N. ; Mikeladze, N. ; Surguladze, S. ; Vincent, J. B. ; Farmer, A. ; Mitchell, P. B. ; Wright, A. ; Schofield, P. R. ; Fullerton, J. M. ; Montgomery, G. W. ; Martin, N. G. ; Rubino, I. A. ; Van Winkel, R. ; Kenis, G. ; De Hert, M. ; Réthelyi, J. M. ; Bitter, I. ; Terenius, L. ; Jönsson, E. G. ; Bakker, S. ; Van Os, J. ; Jablensky, A. ; Leboyer, M. ; Bramon, E. ; Powell, J. ; Murray, R. ; Corvin, A. ; Gill, M. ; Morris, D. ; O'Neill, F. A. ; Kendler, K. ; Riley, B. ; Craddock, N. ; Owen, M. J. ; O'Donovan, M. C. ; Thorsteinsdottir, U. ; Kong, A. ; Ehrenreich, H. ; Carracedo, A. ; Golimbet, V. ; Andreassen, O. A. ; Børglum, A. D. ; Mors, O. ; Mortensen, P. B. ; Werge, T. ; Ophoff, R. A. ; Nöthen, M. M. ; Rietschel, M. ; Cichon, S. ; Ruggeri, M. ; Tosato, S. ; Palotie, A. ; St Clair, D. ; Rujescu, D. ; Collier, D. A. ; Stefansson, H. ; Stefansson, K. / Common variant at 16p11.2 conferring risk of psychosis. In: Molecular Psychiatry. 2014 ; Vol. 19, No. 1. pp. 108-114.
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title = "Common variant at 16p11.2 conferring risk of psychosis",
abstract = "Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255T; odds ratio=1.08; P=6.6 × 10 -11). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255T is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).",
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AU - Steinberg, S.

AU - De Jong, S.

AU - Mattheisen, M.

AU - Costas, J.

AU - Demontis, D.

AU - Jamain, S.

AU - Pietiläinen, O. P H

AU - Lin, K.

AU - Papiol, S.

AU - Huttenlocher, J.

AU - Sigurdsson, E.

AU - Vassos, E.

AU - Giegling, I.

AU - Breuer, R.

AU - Fraser, G.

AU - Walker, N.

AU - Melle, I.

AU - Djurovic, S.

AU - Agartz, I.

AU - Tuulio-Henriksson, A.

AU - Suvisaari, J.

AU - Lönnqvist, J.

AU - Paunio, T.

AU - Olsen, L.

AU - Hansen, T.

AU - Ingason, A.

AU - Pirinen, M.

AU - Strengman, E.

AU - Hougaard, D. M.

AU - Orntoft, T.

AU - Didriksen, M.

AU - Hollegaard, M. V.

AU - Nordentoft, M.

AU - Abramova, L.

AU - Kaleda, V.

AU - Arrojo, M.

AU - Sanjuán, J.

AU - Arango, C.

AU - Etain, B.

AU - Bellivier, F.

AU - Méary, A.

AU - Schürhoff, F.

AU - Szoke, A.

AU - Ribolsi, M.

AU - Magni, V.

AU - Siracusano, A.

AU - Sperling, S.

AU - Rossner, M.

AU - Christiansen, C.

AU - Kiemeney, L. A.

AU - Franke, B.

AU - Van Den Berg, L. H.

AU - Veldink, J.

AU - Curran, S.

AU - Bolton, P.

AU - Poot, M.

AU - Staal, W.

AU - Rehnstrom, K.

AU - Kilpinen, H.

AU - Freitag, C. M.

AU - Meyer, J.

AU - Magnusson, P.

AU - Saemundsen, E.

AU - Martsenkovsky, I.

AU - Bikshaieva, I.

AU - Martsenkovska, I.

AU - Vashchenko, O.

AU - Raleva, M.

AU - Paketchieva, K.

AU - Stefanovski, B.

AU - Durmishi, N.

AU - Pejovic Milovancevic, M.

AU - Lecic Tosevski, D.

AU - Silagadze, T.

AU - Naneishvili, N.

AU - Mikeladze, N.

AU - Surguladze, S.

AU - Vincent, J. B.

AU - Farmer, A.

AU - Mitchell, P. B.

AU - Wright, A.

AU - Schofield, P. R.

AU - Fullerton, J. M.

AU - Montgomery, G. W.

AU - Martin, N. G.

AU - Rubino, I. A.

AU - Van Winkel, R.

AU - Kenis, G.

AU - De Hert, M.

AU - Réthelyi, J. M.

AU - Bitter, I.

AU - Terenius, L.

AU - Jönsson, E. G.

AU - Bakker, S.

AU - Van Os, J.

AU - Jablensky, A.

AU - Leboyer, M.

AU - Bramon, E.

AU - Powell, J.

AU - Murray, R.

AU - Corvin, A.

AU - Gill, M.

AU - Morris, D.

AU - O'Neill, F. A.

AU - Kendler, K.

AU - Riley, B.

AU - Craddock, N.

AU - Owen, M. J.

AU - O'Donovan, M. C.

AU - Thorsteinsdottir, U.

AU - Kong, A.

AU - Ehrenreich, H.

AU - Carracedo, A.

AU - Golimbet, V.

AU - Andreassen, O. A.

AU - Børglum, A. D.

AU - Mors, O.

AU - Mortensen, P. B.

AU - Werge, T.

AU - Ophoff, R. A.

AU - Nöthen, M. M.

AU - Rietschel, M.

AU - Cichon, S.

AU - Ruggeri, M.

AU - Tosato, S.

AU - Palotie, A.

AU - St Clair, D.

AU - Rujescu, D.

AU - Collier, D. A.

AU - Stefansson, H.

AU - Stefansson, K.

PY - 2014/1

Y1 - 2014/1

N2 - Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255T; odds ratio=1.08; P=6.6 × 10 -11). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255T is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

AB - Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255T; odds ratio=1.08; P=6.6 × 10 -11). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255T is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

KW - 16p11.2

KW - association

KW - bipolar disorder

KW - cross-disorder

KW - schizophrenia

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