Microduplications of 16p11.2 are associated with schizophrenia

Jonathan Sebat and colleagues report the association of microduplication on chromosome 16p11.2 with schizophrenia, while the reciprocal microdeletion was associated with autism and developmental disorders. Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders 1 , 2 , 3 . We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls ( P = 1.2 × 10 −5 , OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls ( P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia ( P = 4.8 × 10 −7 ), bipolar disorder ( P = 0.017) and autism ( P = 1.9 × 10 −7 ). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders ( P = 2.3 × 10 −13 ). Head circumference was larger in patients with the microdeletion than in patients with the microduplication ( P = 0.0007).