title: The phenotypic manifestations of rare CNVs in schizophrenia.
abstract: There is compelling evidence for the role of copy number variants (CNVs) in schizophrenia susceptibility, and it has been estimated that up to 2-3% of schizophrenia cases may carry rare CNVs. Despite evidence that these events are associated with an increased risk across categorical neurodevelopmental disorders, there is limited understanding of the impact of CNVs on the core features of disorders like schizophrenia. Our objective was to evaluate associations between rare CNVs in differentially brain expressed (BE) genes and the core features and clinical correlates of schizophrenia. The sample included 386 cases of Irish ancestry with a diagnosis of schizophrenia, at least one rare CNV impacting any gene, and a core set of phenotypic measures. Statistically significant associations between deletions in differentially BE genes were found for family history of mental illness (decreased prevalence of all CNVs and deletions, unadjusted and adjusted) and for paternal age (increase in deletions only, unadjusted, among those with later ages at birth of patient). The strong effect of a lack of a family history on BE genes suggests that CNVs may comprise one pathway to schizophrenia, whereas a positive family history could index other genetic mechanisms that increase schizophrenia vulnerability. To our knowledge, this is the first investigation of the association between genome-wide CNVs and risk factors and sub-phenotypic features of schizophrenia beyond cognitive function.
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland. Electronic address: merikana@tcd.ie.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Merikangas
authors.affiliation: Centre for Support and Training in Analysis and Research, University College Dublin, Dublin 4, Ireland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Segurado
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Cormican
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Heron
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Richard J L
authors.initials: RJ
authors.lastname: Anney
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Moore
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Eric
authors.initials: E
authors.lastname: Kelleher
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: April
authors.initials: A
authors.lastname: Hargreaves
authors.affiliation: Psychiatric Genetics, Department of Psychiatry and Psychotherapy, University Medical Centre, Georg-August-University Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Anderson-Schmidt
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Louise
authors.initials: L
authors.lastname: Gallagher
authors.affiliation: Department of Psychiatry & Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Aiden
authors.initials: A
authors.lastname: Corvin
mesh_terms: D001921:Brain / Q000378:metabolism*; D056915:DNA Copy Number Variations; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007494:Ireland; D016015:Logistic Models; D008297:Male; D010331:Paternal Age; D010641:Phenotype; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D044465:White People / Q000235:genetics
keywords: CNV; Copy number variation; Family history; Paternal age; Phenotype; Schizophrenia