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. Pietilainen; 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-Henriksson; J. Suvisaari; J. Lonnqvist; 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. Sanjuan; C. Arango; B. Etain; F. Bellivier; A. Meary; F. Schuerhoff; 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. Rethelyi; I. Bitter; L. Terenius; E. G. Jonsson; 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. Borglum; O. Mors; P. B. Mortensen; T. Werge; R. A. Ophoff; M. M. Noethen; M. Rietschel; S. Cichon; M. Ruggeri; S. Tosato; A. Palotie; D. St Clair; D. Rujescu; D. A. Collier; H. Stefansson; K. Stefansson

doi:10.1038/mp.2012.157

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. Pietilainen, 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. Lonnqvist, 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. Sanjuan, C. Arango, B. Etain, F. Bellivier, A. Meary, F. Schuerhoff, 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. Rethelyi, I. Bitter, L. Terenius, E. G. Jonsson, 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. Borglum, O. Mors, P. B. Mortensen, T. Werge, R. A. Ophoff, M. M. Noethen, M. Rietschel, S. Cichon, M. Ruggeri, S. Tosato, A. Palotie, D. St Clair, D. Rujescu, D. A. Collier, H. Stefansson, K. Stefansson^*

^*Corresponding author for this work

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

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 (rs4583255[T]; odds ratio = 1.08; P = 6.6 x 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), rs4583255[T] 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 language	English
Pages (from-to)	108-114
Journal	Molecular Psychiatry
Volume	19
Issue number	1
DOIs	https://doi.org/10.1038/mp.2012.157
Publication status	Published - Jan 2014

Keywords

association
bipolar disorder
cross-disorder
schizophrenia
16p11.2

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10.1038/mp.2012.157

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Steinberg, S., de Jong, S., Mattheisen, M., Costas, J., Demontis, D., Jamain, S., Pietilainen, 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., ... 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

@article{6b39442ce2644f17b1f09231087cd1f6,

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 (rs4583255[T]; odds ratio = 1.08; P = 6.6 x 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), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium data set; P = 0.00047 in 22 651 additional Icelanders).",

keywords = "association, bipolar disorder, cross-disorder, schizophrenia, 16p11.2",

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

year = "2014",

month = jan,

doi = "10.1038/mp.2012.157",

language = "English",

volume = "19",

pages = "108--114",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer",

number = "1",

}

Steinberg, S, de Jong, S, Mattheisen, M, Costas, J, Demontis, D, Jamain, S, Pietilainen, 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, Lonnqvist, 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, Sanjuan, J, Arango, C, Etain, B, Bellivier, F, Meary, A, Schuerhoff, 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, Milovancevic, MP, Tosevski, DL, 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, Rethelyi, JM, Bitter, I, Terenius, L, Jonsson, 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, Borglum, AD, Mors, O, Mortensen, PB, Werge, T, Ophoff, RA, Noethen, 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

TY - JOUR

T1 - Common variant at 16p11.2 conferring risk of psychosis

AU - Steinberg, S.

AU - de Jong, S.

AU - Mattheisen, M.

AU - Costas, J.

AU - Demontis, D.

AU - Jamain, S.

AU - Pietilainen, 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 - Lonnqvist, 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 - Sanjuan, J.

AU - Arango, C.

AU - Etain, B.

AU - Bellivier, F.

AU - Meary, A.

AU - Schuerhoff, 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 - Milovancevic, M. Pejovic

AU - Tosevski, D. Lecic

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 - Rethelyi, J. M.

AU - Bitter, I.

AU - Terenius, L.

AU - Jonsson, 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 - Borglum, A. D.

AU - Mors, O.

AU - Mortensen, P. B.

AU - Werge, T.

AU - Ophoff, R. A.

AU - Noethen, 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 (rs4583255[T]; odds ratio = 1.08; P = 6.6 x 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), rs4583255[T] 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 (rs4583255[T]; odds ratio = 1.08; P = 6.6 x 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), rs4583255[T] 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 - association

KW - bipolar disorder

KW - cross-disorder

KW - schizophrenia

KW - 16p11.2

U2 - 10.1038/mp.2012.157

DO - 10.1038/mp.2012.157

M3 - Article

C2 - 23164818

SN - 1359-4184

VL - 19

SP - 108

EP - 114

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 1

ER -

Common variant at 16p11.2 conferring risk of psychosis

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Keywords

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