Implication of a rare deletion at distal 16p11.2 in 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 PriebeRené 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

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)


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 parentoffspring 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.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalJAMA Psychiatry
Issue number3
Publication statusPublished - 03-2013

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health


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