Document Detail

Implication of a rare deletion at distal 16p11.2 in schizophrenia.
MedLine Citation:
PMID:  23325106     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Large genomic copy number variations have been implicated as strong risk factors for schizophrenia. However, the rarity of these events has created challenges for the identification of further pathogenic loci, and extremely large samples are required to provide convincing replication.
OBJECTIVE: To detect novel copy number variations that increase the susceptibility to schizophrenia by using 2 ethnically homogeneous discovery cohorts and replication in large samples.
DESIGN: Genetic association study of microarray data.
SETTING: Samples of DNA were collected at 9 sites from different countries.
PARTICIPANTS: Two discovery cohorts consisted of 790 cases with schizophrenia and schizoaffective disorder and 1347 controls of Ashkenazi Jewish descent and 662 parent-offspring trios from Bulgaria, of which the offspring had schizophrenia or schizoaffective disorder. Replication data sets consisted of 12,398 cases and 17,945 controls.
MAIN OUTCOME MEASURES: Statistically increased rate of specific copy number variations in cases vs controls.
RESULTS: One novel locus was implicated: a deletion at distal 16p11.2, which does not overlap the proximal 16p11.2 locus previously reported in schizophrenia and autism. Deletions at this locus were found in 13 of 13,850 cases (0.094%) and 3 of 19,954 controls (0.015%) (odds ratio, 6.25 [95% CI, 1.78-21.93]; P = .001, Fisher exact test).
CONCLUSIONS: Deletions at distal 16p11.2 have been previously implicated in developmental delay and obesity. The region contains 9 genes, several of which are implicated in neurological diseases, regulation of body weight, and glucose homeostasis. A telomeric extension of the deletion, observed in about half the cases but no controls, potentially implicates an additional 8 genes. Our findings add a new locus to the list of copy number variations that increase the risk for development of schizophrenia.
Saurav Guha; Elliott Rees; Ariel Darvasi; Dobril Ivanov; Masashi Ikeda; Sarah E Bergen; Patrik K Magnusson; Paul Cormican; Derek Morris; Michael Gill; Sven Cichon; Jeffrey A Rosenfeld; Annette Lee; Peter K Gregersen; John M Kane; Anil K Malhotra; Marcella Rietschel; Markus M Nöthen; Franziska Degenhardt; Lutz Priebe; René Breuer; Jana Strohmaier; Douglas M Ruderfer; Jennifer L Moran; Kimberly D Chambert; Alan R Sanders; Jianxin Shi; Kenneth Kendler; Brien Riley; Tony O'Neill; Dermot Walsh; Dheeraj Malhotra; Aiden Corvin; Shaun Purcell; Pamela Sklar; Nakao Iwata; Christina M Hultman; Patrick F Sullivan; Jonathan Sebat; Shane McCarthy; Pablo V Gejman; Douglas F Levinson; Michael J Owen; Michael C O'Donovan; Todd Lencz; George Kirov; ;
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-07     Completed Date:  2013-05-02     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  253-60     Citation Subset:  AIM; IM    
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MeSH Terms
Base Sequence*
Case-Control Studies
Chromosomes, Human, Pair 16 / genetics*
Cohort Studies
DNA Copy Number Variations
Genetic Predisposition to Disease
Psychotic Disorders / genetics*
Risk Factors
Schizophrenia / genetics*
Sequence Deletion*
Grant Support
068545/Z/02//Wellcome Trust; 085475/B/08/Z//Wellcome Trust; 085475/Z/08/Z//Wellcome Trust; 2 P50 MH066392-05A1/MH/NIMH NIH HHS; G0000934//Medical Research Council; G0800509//Medical Research Council; MH46276/MH/NIMH NIH HHS; MH46289/MH/NIMH NIH HHS; MH46318/MH/NIMH NIH HHS; MH59565/MH/NIMH NIH HHS; MH59566/MH/NIMH NIH HHS; MH59571/MH/NIMH NIH HHS; MH59586/MH/NIMH NIH HHS; MH59587/MH/NIMH NIH HHS; MH59588/MH/NIMH NIH HHS; MH60870/MH/NIMH NIH HHS; MH60879/MH/NIMH NIH HHS; MH61675/MH/NIMH NIH HHS; MH67257/MH/NIMH NIH HHS; MH79469/MH/NIMH NIH HHS; MH79470/MH/NIMH NIH HHS; MH81800/MH/NIMH NIH HHS; P30 MH090590/MH/NIMH NIH HHS; P30 MH090590/MH/NIMH NIH HHS; P50 MH066392/MH/NIMH NIH HHS; P50 MH080173/MH/NIMH NIH HHS; P50 MH080173/MH/NIMH NIH HHS; R01 MH059565/MH/NIMH NIH HHS; R01 MH059566/MH/NIMH NIH HHS; R01 MH059571/MH/NIMH NIH HHS; R01 MH059586/MH/NIMH NIH HHS; R01 MH059587/MH/NIMH NIH HHS; R01 MH059588/MH/NIMH NIH HHS; R01 MH060870/MH/NIMH NIH HHS; R01 MH060879/MH/NIMH NIH HHS; R01 MH061675/MH/NIMH NIH HHS; R01 MH067257/MH/NIMH NIH HHS; R01 MH081800/MH/NIMH NIH HHS; R01 MH083094/MH/NIMH NIH HHS; R01 MH084098/MH/NIMH NIH HHS; R01 MH084098/MH/NIMH NIH HHS; R01 MH095034/MH/NIMH NIH HHS; RC2 MH089964/MH/NIMH NIH HHS; RC2 MH089964/MH/NIMH NIH HHS; U01 MH046276-08/MH/NIMH NIH HHS; U01 MH046289-08/MH/NIMH NIH HHS; U01 MH046318/MH/NIMH NIH HHS; U01 MH046318-08/MH/NIMH NIH HHS; U01 MH079469/MH/NIMH NIH HHS; U01 MH079470/MH/NIMH NIH HHS; U01 MH094411/MH/NIMH NIH HHS; U54 RR020278/RR/NCRR NIH HHS; U54 RR020278/RR/NCRR NIH HHS

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