TY - JOUR
T1 - Copy number variations of chromosome 16p13.1 region associated with schizophrenia
AU - Ingason, A.
AU - Rujescu, Dan
AU - Cichon, S.
AU - Sigurdsson, Engilbert
AU - Sigmundsson, T.
AU - Pietilainen, O. P. H.
AU - Buizer-Voskamp, Jacobine E.
AU - Strengman, E.
AU - Francks, Clyde
AU - Muglia, Pierandrea
AU - Gylfason, A.
AU - Gustafsson, Omar
AU - Olason, P. I.
AU - Steinberg, Stacy
AU - Hansen, T.
AU - Jakobsen, Klaus D.
AU - Rasmussen, Henrik B.
AU - Giegling, Ina
AU - Moeller, H-J
AU - Hartmann, A
AU - Crombie, C.
AU - Fraser, G.
AU - Walker, N.
AU - Lonnqvist, Jouko
AU - Suvisaari, J.
AU - Tuulio-Henriksson, A.
AU - Bramon, Elvira
AU - Kiemeney, Lambertus A.
AU - Franke, B.
AU - Murray, R.M.
AU - Vassos, E.
AU - Toulopoulou, Timothea
AU - Muehleisen, Thomas W.
AU - Tosato, Sarah
AU - Ruggeri, M.
AU - Djurovic, Srdjan
AU - Andreassen, Ole A.
AU - Zhang, Z.
AU - Werge, Thomas
AU - Ophoff, Roel A.
AU - Rietschel, M.
AU - Noethen, M. M.
AU - Petursson, Hannes
AU - Stefansson, Hreinn
AU - Peltonen, L.
AU - Collier, David A.
AU - Stefansson, K.
AU - Genetic Risk and Outcome of Psychosis (GROUP) Investigators
AU - van Os, Jim
AU - St Clair, D. M.
PY - 2011/1
Y1 - 2011/1
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.
KW - 16p13.1
KW - CNV
KW - schizophrenia
KW - duplication
U2 - 10.1038/mp.2009.101
DO - 10.1038/mp.2009.101
M3 - Article
C2 - 19786961
SN - 1359-4184
VL - 16
SP - 17
EP - 25
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 1
ER -