학술논문
Microduplications of 16p11.2 are associated with schizophrenia
Document Type
article
Author
McCarthy, Shane E; Makarov, Vladimir; Kirov, George; Addington, Anjene M; McClellan, Jon; Yoon, Seungtai; Perkins, Diana O; Dickel, Diane E; Kusenda, Mary; Krastoshevsky, Olga; Krause, Verena; Kumar, Ravinesh A; Grozeva, Detelina; Malhotra, Dheeraj; Walsh, Tom; Zackai, Elaine H; Kaplan, Paige; Ganesh, Jaya; Krantz, Ian D; Spinner, Nancy B; Roccanova, Patricia; Bhandari, Abhishek; Pavon, Kevin; Lakshmi, B; Leotta, Anthony; Kendall, Jude; Lee, Yoon-ha; Vacic, Vladimir; Gary, Sydney; Iakoucheva, Lilia M; Crow, Timothy J; Christian, Susan L; Lieberman, Jeffrey A; Stroup, T Scott; Lehtimäki, Terho; Puura, Kaija; Haldeman-Englert, Chad; Pearl, Justin; Goodell, Meredith; Willour, Virginia L; DeRosse, Pamela; Steele, Jo; Kassem, Layla; Wolff, Jessica; Chitkara, Nisha; McMahon, Francis J; Malhotra, Anil K; Potash, James B; Schulze, Thomas G; Nöthen, Markus M; Cichon, Sven; Rietschel, Marcella; Leibenluft, Ellen; Kustanovich, Vlad; Lajonchere, Clara M; Sutcliffe, James S; Skuse, David; Gill, Michael; Gallagher, Louise; Mendell, Nancy R; Craddock, Nick; Owen, Michael J; O'Donovan, Michael C; Shaikh, Tamim H; Susser, Ezra; DeLisi, Lynn E; Sullivan, Patrick F; Deutsch, Curtis K; Rapoport, Judith; Levy, Deborah L; King, Mary-Claire; Sebat, Jonathan
Source
Nature Genetics. 41(11)
Subject
Language
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 x 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 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).