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Letter

Nature Genetics 41, 1223–1227 (1 November 2009) | doi:10.1038/ng.474

Microduplications of 16p11.2 are associated with schizophrenia

Shane E McCarthy , Vladimir Makarov , George Kirov , Anjene M Addington , Jon McClellan , Seungtai Yoon , Diana O Perkins , Diane E Dickel , Mary Kusenda , Olga Krastoshevsky , Verena Krause , Ravinesh A Kumar , Detelina Grozeva , Dheeraj Malhotra , Tom Walsh , Elaine H Zackai , Paige Kaplan , Jaya Ganesh , Ian D Krantz , Nancy B Spinner , Patricia Roccanova , Abhishek Bhandari , Kevin Pavon , B Lakshmi , Anthony Leotta , Jude Kendall , Yoon-ha Lee , Vladimir Vacic , Sydney Gary , Lilia M Iakoucheva , Timothy J Crow , Susan L Christian , Jeffrey A Lieberman , T Scott Stroup , Terho Lehtim|[auml]|ki , Kaija Puura , Chad Haldeman-Englert , Justin Pearl , Meredith Goodell , Virginia L Willour , Pamela DeRosse , Jo Steele , Layla Kassem , Jessica Wolff , Nisha Chitkara , Francis J McMahon , Anil K Malhotra , James B Potash , Thomas G Schulze , Markus M N|[ouml]|then , Sven Cichon , Marcella Rietschel , Ellen Leibenluft , Vlad Kustanovich , Clara M Lajonchere , James S Sutcliffe , David Skuse , Michael Gill , Louise Gallagher , Nancy R Mendell , Nick Craddock , Michael J Owen , Michael C O'Donovan , Tamim H Shaikh , Ezra Susser , Lynn E DeLisi , Patrick F Sullivan , Curtis K Deutsch , Judith Rapoport , Deborah L Levy , Mary-Claire King & Jonathan Sebat

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 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 |[times]| 10|[minus]|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 |[times]| 10|[minus]|7), bipolar disorder (P = 0.017) and autism (P = 1.9 |[times]| 10|[minus]|7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 |[times]| 10|[minus]|13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).