Analysis of copy number variations at 15 schizophrenia-associated loci

被引:300
作者
Rees, Elliott [1 ]
Walters, James T. R. [1 ]
Georgieva, Lyudmila [1 ]
Isles, Anthony R. [1 ]
Chambert, Kimberly D. [2 ]
Richards, Alexander L. [3 ]
Mahoney-Davies, Gerwyn [3 ]
Legge, Sophie E. [3 ]
Moran, Jennifer L. [2 ]
McCarroll, Steven A. [2 ]
O'Donovan, Michael C. [3 ]
Owen, Michael J. [3 ]
Kirov, George [1 ,3 ]
机构
[1] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CB24 4HQ, S Glam, Wales
[2] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA
[3] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Ctr Neuropsychiat Genet & Genom, Cardiff CB24 4HQ, S Glam, Wales
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国惠康基金;
关键词
RARE CHROMOSOMAL DELETIONS; RECURRENT MICRODELETIONS; 16P11.2; AUTISM; GENE; CNVS; DUPLICATIONS; PREVALENCE; DISORDERS; VARIANT;
D O I
10.1192/bjp.bp.113.131052
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Background 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. Aims 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. Method 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. Results 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 16011.2 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 x 10(-4)). Conclusions 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.
引用
收藏
页码:108 / 114
页数:7
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