RT Journal
A1 Guha S, Rees E, Darvasi A, et al
T1 IMplication of a rare deletion at distal 16p11.2 in schizophrenia
JF JAMA Psychiatry
JO JAMA Psychiatry
YR 2013
FD March 1
VO 70
IS 3
SP 253
OP 260
DO 10.1001/2013.jamapsychiatry.71
UL http://dx.doi.org/10.1001/2013.jamapsychiatry.71
AB 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.