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

TitleCopy number variations of chromosome 16p13.1 region associated with schizophrenia.
Publication TypeJournal Article
Year of Publication2011
AuthorsIngason, 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
Corporate AuthorsGROUP Investigators
JournalMolecular psychiatry
Volume16
Issue1
Pagination17-25
Date Published2011 Jan
ISSN1476-5578
KeywordsAdolescent, Adult, Case-Control Studies, Child, Chromosome Aberrations, Chromosome Mapping, Chromosomes, Human, Pair 16, DNA Copy Number Variations, Female, Humans, Male, Reference Values, Schizophrenia, Segmental Duplications, Genomic, Sequence Deletion, Young Adult
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.

DOI10.1038/ng.2250
Alternate JournalMol. Psychiatry