Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 cases and 1/3,971 controls from the initial cohort, and in 9/2,645 cases and 1/2,420 controls of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia ) in the combined sample. A meta-analysis of datasets for multiple psychiatric (...) disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders. Head circumference was larger in patients with the microdeletion than in patients with the microduplication. © 2009 Nature America, Inc. All rights reserved. (shrink)