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 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

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 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

Psychology

Cold Spring Harbor Laboratory
Medical Research Council
National Institutes of Health
University of Washington
University of North Carolina at Chapel Hill
Stony Brook University
McLean Hospital
The University of Chicago
Division of Human Genetics
University of Pennsylvania
Ontario Institute for Cancer Research
Rockefeller University
Oxford Health NHS Foundation Trust
Columbia University
Department of Clinical Chemistry
Tampere University
Johns Hopkins University
Zucker Hillside Hospital
Heidelberg University
Life and Brain Center
Institute of Human Genetics
University of Bonn
Autism Speaks Inc.
Vanderbilt University
University College London
Trinity College Dublin
Harvard University
VA Medical Center
University of Massachusetts Medical School

Research output: Contribution to journal › Article › peer-review

608 Scopus citations

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 language	English
Pages (from-to)	1223-1227
Number of pages	5
Journal	Nature Genetics
Volume	41
Issue number	11
DOIs	https://doi.org/10.1038/ng.474
State	Published - Nov 2009

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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

@article{0a22920e74b2439c99b19679f42f1d54,

title = "Microduplications of 16p11.2 are associated with schizophrenia",

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 {\texttimes} 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 {\texttimes} 10 7), bipolar disorder (P = 0.017) and autism (P = 1.9 {\texttimes} 10 7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 {\texttimes} 10 13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).",

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

year = "2009",

month = nov,

doi = "10.1038/ng.474",

language = "English",

volume = "41",

pages = "1223--1227",

journal = "Nature Genetics",

issn = "1061-4036",

number = "11",

}

McCarthy, SE, Makarov, V, Kirov, G, Addington, AM, McClellan, J, Yoon, S, Perkins, DO, Dickel, DE, Kusenda, M, Krastoshevsky, O, Krause, V, Kumar, RA, Grozeva, D, Malhotra, D, Walsh, T, Zackai, EH, Kaplan, P, Ganesh, J, Krantz, ID, Spinner, NB, Roccanova, P, Bhandari, A, Pavon, K, Lakshmi, B, Leotta, A, Kendall, J, Lee, YH, Vacic, V, Gary, S, Iakoucheva, LM, Crow, TJ, Christian, SL, Lieberman, JA, Stroup, TS, Lehtimäki, T, Puura, K, Haldeman-Englert, C, Pearl, J, Goodell, M, Willour, VL, Derosse, P, Steele, J, Kassem, L, Wolff, J, Chitkara, N, McMahon, FJ, Malhotra, AK, Potash, JB, Schulze, TG, Nöthen, MM, Cichon, S, Rietschel, M, Leibenluft, E, Kustanovich, V, Lajonchere, CM, Sutcliffe, JS, Skuse, D, Gill, M, Gallagher, L, Mendell, NR, Craddock, N, Owen, MJ, O'Donovan, MC, Shaikh, TH, Susser, E, Delisi, LE, Sullivan, PF, Deutsch, CK, Rapoport, J, Levy, DL, King, MC & Sebat, J 2009, 'Microduplications of 16p11.2 are associated with schizophrenia', Nature Genetics, vol. 41, no. 11, pp. 1223-1227. https://doi.org/10.1038/ng.474

TY - JOUR

T1 - Microduplications of 16p11.2 are associated with schizophrenia

AU - McCarthy, Shane E.

AU - Makarov, Vladimir

AU - Kirov, George

AU - Addington, Anjene M.

AU - McClellan, Jon

AU - Yoon, Seungtai

AU - Perkins, Diana O.

AU - Dickel, Diane E.

AU - Kusenda, Mary

AU - Krastoshevsky, Olga

AU - Krause, Verena

AU - Kumar, Ravinesh A.

AU - Grozeva, Detelina

AU - Malhotra, Dheeraj

AU - Walsh, Tom

AU - Zackai, Elaine H.

AU - Kaplan, Paige

AU - Ganesh, Jaya

AU - Krantz, Ian D.

AU - Spinner, Nancy B.

AU - Roccanova, Patricia

AU - Bhandari, Abhishek

AU - Pavon, Kevin

AU - Lakshmi, B.

AU - Leotta, Anthony

AU - Kendall, Jude

AU - Lee, Yoon Ha

AU - Vacic, Vladimir

AU - Gary, Sydney

AU - Iakoucheva, Lilia M.

AU - Crow, Timothy J.

AU - Christian, Susan L.

AU - Lieberman, Jeffrey A.

AU - Stroup, T. Scott

AU - Lehtimäki, Terho

AU - Puura, Kaija

AU - Haldeman-Englert, Chad

AU - Pearl, Justin

AU - Goodell, Meredith

AU - Willour, Virginia L.

AU - Derosse, Pamela

AU - Steele, Jo

AU - Kassem, Layla

AU - Wolff, Jessica

AU - Chitkara, Nisha

AU - McMahon, Francis J.

AU - Malhotra, Anil K.

AU - Potash, James B.

AU - Schulze, Thomas G.

AU - Nöthen, Markus M.

AU - Cichon, Sven

AU - Rietschel, Marcella

AU - Leibenluft, Ellen

AU - Kustanovich, Vlad

AU - Lajonchere, Clara M.

AU - Sutcliffe, James S.

AU - Skuse, David

AU - Gill, Michael

AU - Gallagher, Louise

AU - Mendell, Nancy R.

AU - Craddock, Nick

AU - Owen, Michael J.

AU - O'Donovan, Michael C.

AU - Shaikh, Tamim H.

AU - Susser, Ezra

AU - Delisi, Lynn E.

AU - Sullivan, Patrick F.

AU - Deutsch, Curtis K.

AU - Rapoport, Judith

AU - Levy, Deborah L.

AU - King, Mary Claire

AU - Sebat, Jonathan

PY - 2009/11

Y1 - 2009/11

N2 - 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).

AB - 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).

UR - https://www.scopus.com/pages/publications/70350626873

U2 - 10.1038/ng.474

DO - 10.1038/ng.474

M3 - Article

C2 - 19855392

AN - SCOPUS:70350626873

SN - 1061-4036

VL - 41

SP - 1223

EP - 1227

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Microduplications of 16p11.2 are associated with schizophrenia

Abstract

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