title: Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia.
abstract: Childhood-onset schizophrenia (COS) is a rare severe form of schizophrenia that may have greater salient genetic risk. Despite evidence for high heritability, conclusive genetic causes of schizophrenia remain elusive. Recent genomic technologies in concert with large case-control cohorts have led to several associations of highly penetrant rare copy number variants (CNVs) and schizophrenia. We previously reported two patients with COS who carried a microduplication disrupting the PXDN and MYT1L genes at 2p25.3. This rate of duplications within our COS population (N=92) is significantly higher than that in 2026 healthy controls (P=0.002). As a replication, we report a meta-analysis of four recently published studies that together provide strong evidence for an association between variably sized microduplications involving the MYT1L gene and schizophrenia. None have reported this separately. Altogether, among 5325 patients and 9279 controls, 10 microduplications were observed: nine in patients and one in a control (odds ratio=15.7, P=0.001). Further, the 2% rate observed in our COS patients is also significantly higher than the rate in adult-onset cases (0.14%, odds ratio=16.6, P=0.01). This report adds to the growing body of literature implicating rare CNVs as risk factors for schizophrenia and shows that some risk CNVs are more common among extreme early-onset cases.
authors.affiliation: Child Psychiatry Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. Leey2@mail.nih.gov
authors.forename: Yohan
authors.initials: Y
authors.lastname: Lee
authors.forename: Anand
authors.initials: A
authors.lastname: Mattai
authors.forename: Robert
authors.initials: R
authors.lastname: Long
authors.forename: Judith L
authors.initials: JL
authors.lastname: Rapoport
authors.forename: Nitin
authors.initials: N
authors.lastname: Gogtay
authors.forename: Anjené M
authors.initials: AM
authors.lastname: Addington
mesh_terms: D016022:Case-Control Studies; D058674:Chromosome Duplication / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020407:Internet; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C561020:MYT1L protein, human; D009419:Nerve Tissue Proteins; D014157:Transcription Factors