Copy number variations of chromosome 16p13.1 region associated with schizophrenia

A Ingason; D Rujescu; S Cichon; E Sigurdsson; T Sigmundsson; O P H Pietiläinen; J E Buizer-Voskamp; E Strengman; C Francks; P Muglia; A Gylfason; O Gustafsson; P I Olason; S Steinberg; Thomas Folkmann Hansen; K D Jakobsen; H B Rasmussen; I Giegling; H-J Möller; A Hartmann; C Crombie; G Fraser; N Walker; J Lonnqvist; J Suvisaari; A Tuulio-Henriksson; E Bramon; L A Kiemeney; B Franke; R Murray; E Vassos; T Toulopoulou; T W Mühleisen; S Tosato; M Ruggeri; S Djurovic; O A Andreassen; Z Zhang; T Werge; R A Ophoff; M Rietschel; M M Nöthen; H Petursson; H Stefansson; L Peltonen; D Collier; K Stefansson; D M St Clair; GROUP Investigators

doi:10.1038/mp.2009.101

Copy number variations of chromosome 16p13.1 region associated with schizophrenia

A Ingason, D Rujescu, S Cichon, E Sigurdsson, T Sigmundsson, O P H Pietiläinen, J E Buizer-Voskamp, E Strengman, C Francks, P Muglia, A Gylfason, O Gustafsson, P I Olason, S Steinberg, Thomas Folkmann Hansen, K D Jakobsen, H B Rasmussen, I Giegling, H-J Möller, A HartmannC Crombie, G Fraser, N Walker, J Lonnqvist, J Suvisaari, A Tuulio-Henriksson, E Bramon, L A Kiemeney, B Franke, R Murray, E Vassos, T Toulopoulou, T W Mühleisen, S Tosato, M Ruggeri, S Djurovic, O A Andreassen, Z Zhang, T Werge, R A Ophoff, M Rietschel, M M Nöthen, H Petursson, H Stefansson, L Peltonen, D Collier, K Stefansson, D M St Clair, GROUP Investigators

172 Citations (Scopus)

Abstract

Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.

Original language	English
Journal	Molecular Psychiatry
Volume	16
Issue number	1
Pages (from-to)	17-25
Number of pages	9
ISSN	1359-4184
DOIs	https://doi.org/10.1038/mp.2009.101 https://doi.org/10.1038/mp.2009.101
Publication status	Published - 1 Jan 2011

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Ingason, A., Rujescu, D., Cichon, S., Sigurdsson, E., Sigmundsson, T., Pietiläinen, O. P. H., Buizer-Voskamp, J. E., Strengman, E., Francks, C., Muglia, P., Gylfason, A., Gustafsson, O., Olason, P. I., Steinberg, S., Hansen, T. F., Jakobsen, K. D., Rasmussen, H. B., Giegling, I., Möller, H.-J., ... GROUP Investigators (2011). Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Molecular Psychiatry, 16(1), 17-25. https://doi.org/10.1038/mp.2009.101, https://doi.org/10.1038/mp.2009.101

Ingason, A, Rujescu, D, Cichon, S, Sigurdsson, E, Sigmundsson, T, Pietiläinen, OPH, Buizer-Voskamp, JE, Strengman, E, Francks, C, Muglia, P, Gylfason, A, Gustafsson, O, Olason, PI, Steinberg, S, Hansen, TF, Jakobsen, KD, Rasmussen, HB, Giegling, I, Möller, H-J, Hartmann, A, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Bramon, E, Kiemeney, LA, Franke, B, Murray, R, Vassos, E, Toulopoulou, T, Mühleisen, TW, Tosato, S, Ruggeri, M, Djurovic, S, Andreassen, OA, Zhang, Z, Werge, T, Ophoff, RA, Rietschel, M, Nöthen, MM, Petursson, H, Stefansson, H, Peltonen, L, Collier, D, Stefansson, K, St Clair, DM & GROUP Investigators 2011, 'Copy number variations of chromosome 16p13.1 region associated with schizophrenia', Molecular Psychiatry, vol. 16, no. 1, pp. 17-25. https://doi.org/10.1038/mp.2009.101, https://doi.org/10.1038/mp.2009.101

@article{cffba0c807e241b68605e1166f8618b1,

title = "Copy number variations of chromosome 16p13.1 region associated with schizophrenia",

abstract = "Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.",

author = "A Ingason and D Rujescu and S Cichon and E Sigurdsson and T Sigmundsson and Pietil{\"a}inen, {O P H} and Buizer-Voskamp, {J E} and E Strengman and C Francks and P Muglia and A Gylfason and O Gustafsson and Olason, {P I} and S Steinberg and Hansen, {Thomas Folkmann} and Jakobsen, {K D} and Rasmussen, {H B} and I Giegling and H-J M{\"o}ller and A Hartmann and C Crombie and G Fraser and N Walker and J Lonnqvist and J Suvisaari and A Tuulio-Henriksson and E Bramon and Kiemeney, {L A} and B Franke and R Murray and E Vassos and T Toulopoulou and M{\"u}hleisen, {T W} and S Tosato and M Ruggeri and S Djurovic and Andreassen, {O A} and Z Zhang and T Werge and Ophoff, {R A} and M Rietschel and N{\"o}then, {M M} and H Petursson and H Stefansson and L Peltonen and D Collier and K Stefansson and {St Clair}, {D M} and Thomas Werge",

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doi = "10.1038/mp.2009.101",

language = "English",

volume = "16",

pages = "17--25",

journal = "Molecular Psychiatry",

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T1 - Copy number variations of chromosome 16p13.1 region associated with schizophrenia

AU - Ingason, A

AU - Rujescu, D

AU - Cichon, S

AU - Sigurdsson, E

AU - Sigmundsson, T

AU - Pietiläinen, O P H

AU - Buizer-Voskamp, J E

AU - Strengman, E

AU - Francks, C

AU - Muglia, P

AU - Gylfason, A

AU - Gustafsson, O

AU - Olason, P I

AU - Steinberg, S

AU - Hansen, Thomas Folkmann

AU - Jakobsen, K D

AU - Rasmussen, H B

AU - Giegling, I

AU - Möller, H-J

AU - Hartmann, A

AU - Crombie, C

AU - Fraser, G

AU - Walker, N

AU - Lonnqvist, J

AU - Suvisaari, J

AU - Tuulio-Henriksson, A

AU - Bramon, E

AU - Kiemeney, L A

AU - Franke, B

AU - Murray, R

AU - Vassos, E

AU - Toulopoulou, T

AU - Mühleisen, T W

AU - Tosato, S

AU - Ruggeri, M

AU - Djurovic, S

AU - Andreassen, O A

AU - Zhang, Z

AU - Werge, T

AU - Ophoff, R A

AU - Rietschel, M

AU - Nöthen, M M

AU - Petursson, H

AU - Stefansson, H

AU - Peltonen, L

AU - Collier, D

AU - Stefansson, K

AU - St Clair, D M

AU - GROUP Investigators

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.

AB - Deletions and reciprocal duplications of the chromosome 16p13.1 region have recently been reported in several cases of autism and mental retardation (MR). As genomic copy number variants found in these two disorders may also associate with schizophrenia, we examined 4345 schizophrenia patients and 35,079 controls from 8 European populations for duplications and deletions at the 16p13.1 locus, using microarray data. We found a threefold excess of duplications and deletions in schizophrenia cases compared with controls, with duplications present in 0.30% of cases versus 0.09% of controls (P=0.007) and deletions in 0.12 % of cases and 0.04% of controls (P>0.05). The region can be divided into three intervals defined by flanking low copy repeats. Duplications spanning intervals I and II showed the most significant (P = 0.00010) association with schizophrenia. The age of onset in duplication and deletion carriers among cases ranged from 12 to 35 years, and the majority were males with a family history of psychiatric disorders. In a single Icelandic family, a duplication spanning intervals I and II was present in two cases of schizophrenia, and individual cases of alcoholism, attention deficit hyperactivity disorder and dyslexia. Candidate genes in the region include NTAN1 and NDE1. We conclude that duplications and perhaps also deletions of chromosome 16p13.1, previously reported to be associated with autism and MR, also confer risk of schizophrenia.

U2 - 10.1038/mp.2009.101

DO - 10.1038/mp.2009.101

M3 - Journal article

C2 - 19786961

SN - 1359-4184

VL - 16

SP - 17

EP - 25

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 1

ER -

Copy number variations of chromosome 16p13.1 region associated with schizophrenia

Abstract

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