1. Microduplications of 16p11.2 are associated with schizophrenia
- Author
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Abhishek Bhandari, Patricia Roccanova, Virginia L. Willour, Shane McCarthy, Verena Krause, Ian D. Krantz, Clara Lajonchere, James S. Sutcliffe, Michael Conlon O'Donovan, Jeffrey A. Lieberman, D. Grozeva, James B. Potash, Markus M. Nöthen, Anil K. Malhotra, Layla Kassem, Olga Krastoshevsky, Jon McClellan, Elaine H. Zackai, Seungtai Yoon, Mary Claire King, Jo Steele, Vlad Kustanovich, Chad R. Haldeman-Englert, Michael Gill, Ellen Leibenluft, Jonathan Sebat, Michael John Owen, Sven Cichon, Nancy B. Spinner, Mary Kusenda, Jessica Wolff, Yoon-ha Lee, Ezra Susser, Vladimir Vacic, Nancy R. Mendell, Marcella Rietschel, Ravinesh A. Kumar, David Skuse, Nisha Chitkara, Thomas G. Schulze, Timothy J. Crow, Vladimir Makarov, Lilia M. Iakoucheva, Jaya Ganesh, B. Lakshmi, Lynn E. DeLisi, Jude Kendall, Tamim H. Shaikh, Kevin Pavon, Susan L. Christian, Kaija Puura, Sydney Gary, Anjené M. Addington, Nicholas John Craddock, Meredith Goodell, Terho Lehtimäki, T. Scott Stroup, Francis J. McMahon, Curtis K. Deutsch, George Kirov, Louise Gallagher, Patrick F. Sullivan, Tom Walsh, Diana O. Perkins, Pamela DeRosse, Justin Pearl, Paige Kaplan, Diane E. Dickel, Judith L. Rapoport, Anthony Leotta, Deborah L. Levy, and Dheeraj Malhotra
- Subjects
medicine.medical_specialty ,Psychosis ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Gene Duplication ,Internal medicine ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Copy-number variation ,Bipolar disorder ,030304 developmental biology ,0303 health sciences ,medicine.disease ,Schizophrenia ,Autism spectrum disorder ,Meta-analysis ,Cohort ,Autism ,Chromosomes, Human, Pair 16 ,030217 neurology & neurosurgery - Abstract
Recurrent microdeletions and microduplications of a 600 kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1-3. Here we report the strong association of 16p11.2 microduplications with schizophrenia in two large cohorts. In the primary sample, the microduplication was detected in 12/1906 (0.63%) cases and 1/3971 (0.03%) controls (P=1.2×10-5, OR=25.8). In the replication sample, the microduplication was detected in 9/2645 (0.34%) cases and 1/2420 (0.04%) controls (P=0.022, OR=8.3). For the series combined, microduplication of 16p11.2 was associated with 14.5-fold increased risk of schizophrenia (95% C.I. [3.3, 62]). A meta-analysis of multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder and autism. The reciprocal microdeletion was associated only with autism and developmental disorders. Analysis of patient clinical data showed that head circumference was significantly larger in patients with the microdeletion compared with patients with the microduplication (P = 0.0007). Our results suggest that the microduplication of 16p11.2 confers substantial risk for schizophrenia and other psychiatric disorders, whereas the reciprocal microdeletion is associated with contrasting clinical features.
- Published
- 2009