Analysis of copy number variations at 15 schizophrenia-associated loci

• Published in: British journal of psychiatry Vol. 204; no. 2; pp. 108 - 114
• Main Authors: REES, Elliott, WALTERS, James T. R, O'DONOVAN, Michael C, OWEN, Michael J, KIROV, George, GEORGIEVA, Lyudmila, ISLES, Anthony R, CHAMBERT, Kimberly D, RICHARDS, Alexander L, MAHONEY-DAVIES, Gerwyn, LEGGE, Sophie E, MORAN, Jennifer L, MCCARROLL, Steven A
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.02.2014; Royal College of Psychiatrists
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Angelman Syndrome - genetics; Biological and medical sciences; Case-Control Studies; Chromosome Deletion; Comorbidity; DNA Copy Number Variations - genetics; Female; Genetic Loci - genetics; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Genomic Imprinting; Genotyping Techniques; Humans; Male; Medical sciences; Middle Aged; Prader-Willi syndrome; Prader-Willi Syndrome - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; Screening; Susceptibility; Variants; Young Adult; Psychosis; Schizophrenia; Genetics; Copy number; Genetic determinism; Polymorphism
• ISSN: 0007-1250; 1472-1465; 1472-1465
• DOI: 10.1192/bjp.bp.113.131052

A number of copy number variants (CNVs) have been suggested as susceptibility factors for schizophrenia. For some of these the data remain equivocal, and the frequency in individuals with schizophrenia is uncertain. To determine the contribution of CNVs at 15 schizophrenia-associated loci (a) using a large new data-set of patients with schizophrenia (n = 6882) and controls (n = 6316), and (b) combining our results with those from previous studies. We used Illumina microarrays to analyse our data. Analyses were restricted to 520 766 probes common to all arrays used in the different data-sets. We found higher rates in participants with schizophrenia than in controls for 13 of the 15 previously implicated CNVs. Six were nominally significantly associated (P<0.05) in this new data-set: deletions at 1q21.1, NRXN1, 15q11.2 and 22q11.2 and duplications at 16p11.2 and the Angelman/Prader-Willi Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were of maternal origin. When combined with published data, 11 of the 15 loci showed highly significant evidence for association with schizophrenia (P<4.1×10(-4)). We strengthen the support for the majority of the previously implicated CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9% of controls carry a large, detectable CNV at one of these loci. Routine CNV screening may be clinically appropriate given the high rate of known deleterious mutations in the disorder and the comorbidity associated with these heritable mutations.