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. SpinnerPatricia 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 Lehtimäki, 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. Nöthen, 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

Research output: Contribution to journalArticle

Abstract

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 × 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).

Original languageEnglish (US)
Pages (from-to)1223-1227
Number of pages5
JournalNature genetics
Volume41
Issue number11
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Genetics

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McCarthy, S. E., Makarov, V., Kirov, G., Addington, A. M., McClellan, J., Yoon, S., Perkins, D. O., Dickel, D. E., Kusenda, M., Krastoshevsky, O., Krause, V., Kumar, R. A., Grozeva, D., Malhotra, D., Walsh, T., Zackai, E. H., Kaplan, P., Ganesh, J., Krantz, I. D., ... Sebat, J. (2009). Microduplications of 16p11.2 are associated with schizophrenia. Nature genetics, 41(11), 1223-1227. https://doi.org/10.1038/ng.474