Expanding the range of ZNF804A variants conferring risk of psychosis

S. Steinberg, O. Mors, A. D. Børglum, O. Gustafsson, T. Werge, P. B. Mortensen, O. A. Andreassen, E. Sigurdsson, T. E. Thorgeirsson, Y. Böttcher, P. Olason, R. A. Ophoff, S. Cichon, I. H. Gudjonsdottir, O. P. H. Pietiläinen, M. Nyegaard, A. Tuulio-Henriksson, A. Ingason, T. Hansen, L. Athanasiu & 52 others J. Suvisaari, J. Lonnqvist, T. Paunio, A. Hartmann, G. Jürgens, M. Nordentoft, D. Hougaard, B. Norgaard-Pedersen, R. Breuer, H.-J. Möller, I. Giegling, B. Glenthøj, H. B. Rasmussen, M. Mattheisen, I. Bitter, J. M. Réthelyi, T. Sigmundsson, R. Fossdal, U. Thorsteinsdottir, M. Ruggeri, S. Tosato, E. Strengman, L. A. Kiemeney, I. Melle, S. Djurovic, L. Abramova, V. Kaleda, M. Walshe, E. Bramon, E. Vassos, T. Li, G. Fraser, N. Walker, T. Toulopoulou, J. Yoon, N. B. Freimer, R. M. Cantor, R. Murray, A. Kong, V. Golimbet, E. G. Jönsson, L. Terenius, I. Agartz, H. Petursson, M. M. Nöthen, M. Rietschel, L. Peltonen, D. Rujescu, D. A. Collier, H. Stefansson, D. St Clair, K. Stefansson

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Abstract

A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10-8) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10-7, and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10-8. In this study, using 5164 schizophrenia cases and 20¿709 controls, we replicated the association with schizophrenia (odds ratio OR=1.08, P=0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N=609, OR=1.09, P=0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]—common and with low relative risk—may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39¿481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P=0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P=0.0016 for association with the larger set of psychiatric disorders).
Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalMolecular Psychiatry
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 2011

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Psychotic Disorders
Schizophrenia
Bipolar Disorder
Psychiatry
Genome-Wide Association Study
Introns
Anxiety
Alleles
Odds Ratio

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Steinberg, S., Mors, O., Børglum, A. D., Gustafsson, O., Werge, T., Mortensen, P. B., ... Stefansson, K. (2011). Expanding the range of ZNF804A variants conferring risk of psychosis. Molecular Psychiatry, 16(1), 59-66. https://doi.org/10.1038/mp.2009.149

Expanding the range of ZNF804A variants conferring risk of psychosis. / Steinberg, S.; Mors, O.; Børglum, A. D.; Gustafsson, O.; Werge, T.; Mortensen, P. B.; Andreassen, O. A.; Sigurdsson, E.; Thorgeirsson, T. E.; Böttcher, Y.; Olason, P.; Ophoff, R. A.; Cichon, S.; Gudjonsdottir, I. H.; Pietiläinen, O. P. H.; Nyegaard, M.; Tuulio-Henriksson, A.; Ingason, A.; Hansen, T.; Athanasiu, L.; Suvisaari, J.; Lonnqvist, J.; Paunio, T.; Hartmann, A.; Jürgens, G.; Nordentoft, M.; Hougaard, D.; Norgaard-Pedersen, B.; Breuer, R.; Möller, H.-J.; Giegling, I.; Glenthøj, B.; Rasmussen, H. B.; Mattheisen, M.; Bitter, I.; Réthelyi, J. M.; Sigmundsson, T.; Fossdal, R.; Thorsteinsdottir, U.; Ruggeri, M.; Tosato, S.; Strengman, E.; Kiemeney, L. A.; Melle, I.; Djurovic, S.; Abramova, L.; Kaleda, V.; Walshe, M.; Bramon, E.; Vassos, E.; Li, T.; Fraser, G.; Walker, N.; Toulopoulou, T.; Yoon, J.; Freimer, N. B.; Cantor, R. M.; Murray, R.; Kong, A.; Golimbet, V.; Jönsson, E. G.; Terenius, L.; Agartz, I.; Petursson, H.; Nöthen, M. M.; Rietschel, M.; Peltonen, L.; Rujescu, D.; Collier, D. A.; Stefansson, H.; St Clair, D.; Stefansson, K.

In: Molecular Psychiatry, Vol. 16, No. 1, 01.2011, p. 59-66.

Research output: Contribution to journalArticle

Steinberg, S, Mors, O, Børglum, AD, Gustafsson, O, Werge, T, Mortensen, PB, Andreassen, OA, Sigurdsson, E, Thorgeirsson, TE, Böttcher, Y, Olason, P, Ophoff, RA, Cichon, S, Gudjonsdottir, IH, Pietiläinen, OPH, Nyegaard, M, Tuulio-Henriksson, A, Ingason, A, Hansen, T, Athanasiu, L, Suvisaari, J, Lonnqvist, J, Paunio, T, Hartmann, A, Jürgens, G, Nordentoft, M, Hougaard, D, Norgaard-Pedersen, B, Breuer, R, Möller, H-J, Giegling, I, Glenthøj, B, Rasmussen, HB, Mattheisen, M, Bitter, I, Réthelyi, JM, Sigmundsson, T, Fossdal, R, Thorsteinsdottir, U, Ruggeri, M, Tosato, S, Strengman, E, Kiemeney, LA, Melle, I, Djurovic, S, Abramova, L, Kaleda, V, Walshe, M, Bramon, E, Vassos, E, Li, T, Fraser, G, Walker, N, Toulopoulou, T, Yoon, J, Freimer, NB, Cantor, RM, Murray, R, Kong, A, Golimbet, V, Jönsson, EG, Terenius, L, Agartz, I, Petursson, H, Nöthen, MM, Rietschel, M, Peltonen, L, Rujescu, D, Collier, DA, Stefansson, H, St Clair, D & Stefansson, K 2011, 'Expanding the range of ZNF804A variants conferring risk of psychosis' Molecular Psychiatry, vol. 16, no. 1, pp. 59-66. https://doi.org/10.1038/mp.2009.149
Steinberg S, Mors O, Børglum AD, Gustafsson O, Werge T, Mortensen PB et al. Expanding the range of ZNF804A variants conferring risk of psychosis. Molecular Psychiatry. 2011 Jan;16(1):59-66. https://doi.org/10.1038/mp.2009.149
Steinberg, S. ; Mors, O. ; Børglum, A. D. ; Gustafsson, O. ; Werge, T. ; Mortensen, P. B. ; Andreassen, O. A. ; Sigurdsson, E. ; Thorgeirsson, T. E. ; Böttcher, Y. ; Olason, P. ; Ophoff, R. A. ; Cichon, S. ; Gudjonsdottir, I. H. ; Pietiläinen, O. P. H. ; Nyegaard, M. ; Tuulio-Henriksson, A. ; Ingason, A. ; Hansen, T. ; Athanasiu, L. ; Suvisaari, J. ; Lonnqvist, J. ; Paunio, T. ; Hartmann, A. ; Jürgens, G. ; Nordentoft, M. ; Hougaard, D. ; Norgaard-Pedersen, B. ; Breuer, R. ; Möller, H.-J. ; Giegling, I. ; Glenthøj, B. ; Rasmussen, H. B. ; Mattheisen, M. ; Bitter, I. ; Réthelyi, J. M. ; Sigmundsson, T. ; Fossdal, R. ; Thorsteinsdottir, U. ; Ruggeri, M. ; Tosato, S. ; Strengman, E. ; Kiemeney, L. A. ; Melle, I. ; Djurovic, S. ; Abramova, L. ; Kaleda, V. ; Walshe, M. ; Bramon, E. ; Vassos, E. ; Li, T. ; Fraser, G. ; Walker, N. ; Toulopoulou, T. ; Yoon, J. ; Freimer, N. B. ; Cantor, R. M. ; Murray, R. ; Kong, A. ; Golimbet, V. ; Jönsson, E. G. ; Terenius, L. ; Agartz, I. ; Petursson, H. ; Nöthen, M. M. ; Rietschel, M. ; Peltonen, L. ; Rujescu, D. ; Collier, D. A. ; Stefansson, H. ; St Clair, D. ; Stefansson, K. / Expanding the range of ZNF804A variants conferring risk of psychosis. In: Molecular Psychiatry. 2011 ; Vol. 16, No. 1. pp. 59-66.
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abstract = "A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10-8) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10-7, and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10-8. In this study, using 5164 schizophrenia cases and 20¿709 controls, we replicated the association with schizophrenia (odds ratio OR=1.08, P=0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N=609, OR=1.09, P=0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]—common and with low relative risk—may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39¿481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P=0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P=0.0016 for association with the larger set of psychiatric disorders).",
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T1 - Expanding the range of ZNF804A variants conferring risk of psychosis

AU - Steinberg, S.

AU - Mors, O.

AU - Børglum, A. D.

AU - Gustafsson, O.

AU - Werge, T.

AU - Mortensen, P. B.

AU - Andreassen, O. A.

AU - Sigurdsson, E.

AU - Thorgeirsson, T. E.

AU - Böttcher, Y.

AU - Olason, P.

AU - Ophoff, R. A.

AU - Cichon, S.

AU - Gudjonsdottir, I. H.

AU - Pietiläinen, O. P. H.

AU - Nyegaard, M.

AU - Tuulio-Henriksson, A.

AU - Ingason, A.

AU - Hansen, T.

AU - Athanasiu, L.

AU - Suvisaari, J.

AU - Lonnqvist, J.

AU - Paunio, T.

AU - Hartmann, A.

AU - Jürgens, G.

AU - Nordentoft, M.

AU - Hougaard, D.

AU - Norgaard-Pedersen, B.

AU - Breuer, R.

AU - Möller, H.-J.

AU - Giegling, I.

AU - Glenthøj, B.

AU - Rasmussen, H. B.

AU - Mattheisen, M.

AU - Bitter, I.

AU - Réthelyi, J. M.

AU - Sigmundsson, T.

AU - Fossdal, R.

AU - Thorsteinsdottir, U.

AU - Ruggeri, M.

AU - Tosato, S.

AU - Strengman, E.

AU - Kiemeney, L. A.

AU - Melle, I.

AU - Djurovic, S.

AU - Abramova, L.

AU - Kaleda, V.

AU - Walshe, M.

AU - Bramon, E.

AU - Vassos, E.

AU - Li, T.

AU - Fraser, G.

AU - Walker, N.

AU - Toulopoulou, T.

AU - Yoon, J.

AU - Freimer, N. B.

AU - Cantor, R. M.

AU - Murray, R.

AU - Kong, A.

AU - Golimbet, V.

AU - Jönsson, E. G.

AU - Terenius, L.

AU - Agartz, I.

AU - Petursson, H.

AU - Nöthen, M. M.

AU - Rietschel, M.

AU - Peltonen, L.

AU - Rujescu, D.

AU - Collier, D. A.

AU - Stefansson, H.

AU - St Clair, D.

AU - Stefansson, K.

PY - 2011/1

Y1 - 2011/1

N2 - A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10-8) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10-7, and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10-8. In this study, using 5164 schizophrenia cases and 20¿709 controls, we replicated the association with schizophrenia (odds ratio OR=1.08, P=0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N=609, OR=1.09, P=0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]—common and with low relative risk—may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39¿481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P=0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P=0.0016 for association with the larger set of psychiatric disorders).

AB - A trio of genome-wide association studies recently reported sequence variants at three loci to be significantly associated with schizophrenia. No sequence polymorphism had been unequivocally (P<5 × 10-8) associated with schizophrenia earlier. However, one variant, rs1344706[T], had come very close. This polymorphism, located in an intron of ZNF804A, was reported to associate with schizophrenia with a P-value of 1.6 × 10-7, and with psychosis (schizophrenia plus bipolar disorder) with a P-value of 1.0 × 10-8. In this study, using 5164 schizophrenia cases and 20¿709 controls, we replicated the association with schizophrenia (odds ratio OR=1.08, P=0.0029) and, by adding bipolar disorder patients, we also confirmed the association with psychosis (added N=609, OR=1.09, P=0.00065). Furthermore, as it has been proposed that variants such as rs1344706[T]—common and with low relative risk—may also serve to identify regions harboring less common, higher-risk susceptibility alleles, we searched ZNF804A for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients with other psychiatric disorders and 39¿481 controls. We identified two CNVs including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in controls (P=0.013 for association with psychosis). In addition, we found a ZNF804A CNV in an anxiety patient (P=0.0016 for association with the larger set of psychiatric disorders).

U2 - 10.1038/mp.2009.149

DO - 10.1038/mp.2009.149

M3 - Article

VL - 16

SP - 59

EP - 66

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

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