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, T Hansen, K D Jakobsen, H B Rasmussen, I Giegling, H-J Möller, A Hartmann & 29 others Catriona Crombie, G Fraser, Nicholas 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, David Malcolm St Clair, GROUP Investigators

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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.Molecular Psychiatry advance online publication, 29 September 2009; doi:10.1038/mp.2009.101.
Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalMolecular Psychiatry
Volume16
Issue number1
DOIs
Publication statusPublished - 2011

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Schizophrenia
Chromosomes
Autistic Disorder
Intellectual Disability
Psychiatry
Genomic Segmental Duplications
Chromosome Duplication
Chromosome Deletion
Dyslexia
Attention Deficit Disorder with Hyperactivity
Age of Onset
Alcoholism
Publications
Population
Genes

Cite this

Ingason, A., Rujescu, D., Cichon, S., Sigurdsson, E., Sigmundsson, T., Pietiläinen, O. P. H., ... 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

Copy number variations of chromosome 16p13.1 region associated with schizophrenia. / 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; Jakobsen, K D; Rasmussen, H B; Giegling, I; Möller, H-J; Hartmann, A; Crombie, Catriona; Fraser, G; Walker, Nicholas; Lonnqvist, J; Suvisaari, J; Tuulio-Henriksson, A; Bramon, E; Kiemeney, L A; Franke, B; Murray, R; Vassos, E; Toulopoulou, T; Mühleisen, T W; Tosato, S; Ruggeri, M; Djurovic, S; Andreassen, O A; Zhang, Z; Werge, T; Ophoff, R A; Rietschel, M; Nöthen, M M; Petursson, H; Stefansson, H; Peltonen, L; Collier, D; Stefansson, K; St Clair, David Malcolm; GROUP Investigators.

In: Molecular Psychiatry, Vol. 16, No. 1, 2011, p. 17-25.

Research output: Contribution to journalArticle

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, T, 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
Ingason A, Rujescu D, Cichon S, Sigurdsson E, Sigmundsson T, Pietiläinen OPH et al. Copy number variations of chromosome 16p13.1 region associated with schizophrenia. Molecular Psychiatry. 2011;16(1):17-25. https://doi.org/10.1038/mp.2009.101
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 ; Jakobsen, K D ; Rasmussen, H B ; Giegling, I ; Möller, H-J ; Hartmann, A ; Crombie, Catriona ; Fraser, G ; Walker, Nicholas ; Lonnqvist, J ; Suvisaari, J ; Tuulio-Henriksson, A ; Bramon, E ; Kiemeney, L A ; Franke, B ; Murray, R ; Vassos, E ; Toulopoulou, T ; Mühleisen, T W ; Tosato, S ; Ruggeri, M ; Djurovic, S ; Andreassen, O A ; Zhang, Z ; Werge, T ; Ophoff, R A ; Rietschel, M ; Nöthen, M M ; Petursson, H ; Stefansson, H ; Peltonen, L ; Collier, D ; Stefansson, K ; St Clair, David Malcolm ; GROUP Investigators. / Copy number variations of chromosome 16p13.1 region associated with schizophrenia. In: Molecular Psychiatry. 2011 ; Vol. 16, No. 1. pp. 17-25.
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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, T

AU - Jakobsen, K D

AU - Rasmussen, H B

AU - Giegling, I

AU - Möller, H-J

AU - Hartmann, A

AU - Crombie, Catriona

AU - Fraser, G

AU - Walker, Nicholas

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, David Malcolm

AU - GROUP Investigators

PY - 2011

Y1 - 2011

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.Molecular Psychiatry advance online publication, 29 September 2009; doi:10.1038/mp.2009.101.

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.Molecular Psychiatry advance online publication, 29 September 2009; doi:10.1038/mp.2009.101.

U2 - 10.1038/mp.2009.101

DO - 10.1038/mp.2009.101

M3 - Article

VL - 16

SP - 17

EP - 25

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 1

ER -