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; 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

doi:10.1038/mp.2009.149

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. AthanasiuJ. 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

Applied Medicine

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

134 Citations (Scopus)

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 language	English
Pages (from-to)	59-66
Number of pages	8
Journal	Molecular Psychiatry
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/mp.2009.149
Publication status	Published - Jan 2011

Access to Document

10.1038/mp.2009.149

Cite this

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., ... 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

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

@article{f0841e09052f4567ab120fdea219045b,

title = "Expanding the range of ZNF804A variants conferring risk of psychosis",

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).",

author = "S. Steinberg and O. Mors and B{\o}rglum, {A. D.} and O. Gustafsson and T. Werge and Mortensen, {P. B.} and Andreassen, {O. A.} and E. Sigurdsson and Thorgeirsson, {T. E.} and Y. B{\"o}ttcher and P. Olason and Ophoff, {R. A.} and S. Cichon and Gudjonsdottir, {I. H.} and Pietil{\"a}inen, {O. P. H.} and M. Nyegaard and A. Tuulio-Henriksson and A. Ingason and T. Hansen and L. Athanasiu and J. Suvisaari and J. Lonnqvist and T. Paunio and A. Hartmann and G. J{\"u}rgens and M. Nordentoft and D. Hougaard and B. Norgaard-Pedersen and R. Breuer and H.-J. M{\"o}ller and I. Giegling and B. Glenth{\o}j and Rasmussen, {H. B.} and M. Mattheisen and I. Bitter and R{\'e}thelyi, {J. M.} and T. Sigmundsson and R. Fossdal and U. Thorsteinsdottir and M. Ruggeri and S. Tosato and E. Strengman and Kiemeney, {L. A.} and I. Melle and S. Djurovic and L. Abramova and V. Kaleda and M. Walshe and E. Bramon and E. Vassos and T. Li and G. Fraser and N. Walker and T. Toulopoulou and J. Yoon and Freimer, {N. B.} and Cantor, {R. M.} and R. Murray and A. Kong and V. Golimbet and J{\"o}nsson, {E. G.} and L. Terenius and I. Agartz and H. Petursson and N{\"o}then, {M. M.} and M. Rietschel and L. Peltonen and D. Rujescu and Collier, {D. A.} and H. Stefansson and {St Clair}, D. and K. Stefansson",

year = "2011",

month = jan,

doi = "10.1038/mp.2009.149",

language = "English",

volume = "16",

pages = "59--66",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

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

C2 - 20048749

SN - 1359-4184

VL - 16

SP - 59

EP - 66

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 1

ER -

Expanding the range of ZNF804A variants conferring risk of psychosis

Abstract

Access to Document

Fingerprint

Cite this