Microduplications of 16p11.2 are associated with schizophrenia.
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).
McCarthy
Shane E
SE
Makarov
Vladimir
V
Kirov
George
G
Addington
Anjene M
AM
McClellan
Jon
J
Yoon
Seungtai
S
Perkins
Diana O
DO
Dickel
Diane E
DE
Kusenda
Mary
M
Krastoshevsky
Olga
O
Krause
Verena
V
Kumar
Ravinesh A
RA
Grozeva
Detelina
D
Malhotra
Dheeraj
D
Walsh
Tom
T
Zackai
Elaine H
EH
Kaplan
Paige
P
Ganesh
Jaya
J
Krantz
Ian D
ID
Spinner
Nancy B
NB
Roccanova
Patricia
P
Bhandari
Abhishek
A
Pavon
Kevin
K
Lakshmi
B
B
Leotta
Anthony
A
Kendall
Jude
J
Lee
Yoon-Ha
YH
Vacic
Vladimir
V
Gary
Sydney
S
Iakoucheva
Lilia M
LM
Crow
Timothy J
TJ
Christian
Susan L
SL
Lieberman
Jeffrey A
JA
Stroup
T Scott
TS
Lehtimäki
Terho
T
Puura
Kaija
K
Haldeman-Englert
Chad
C
Pearl
Justin
J
Goodell
Meredith
M
Willour
Virginia L
VL
Derosse
Pamela
P
Steele
Jo
J
Kassem
Layla
L
Wolff
Jessica
J
Chitkara
Nisha
N
McMahon
Francis J
FJ
Malhotra
Anil K
AK
Potash
James B
JB
Schulze
Thomas G
TG
Nöthen
Markus M
MM
Cichon
Sven
S
Rietschel
Marcella
M
Leibenluft
Ellen
E
Kustanovich
Vlad
V
Lajonchere
Clara M
CM
Sutcliffe
James S
JS
Skuse
David
D
Gill
Michael
M
Gallagher
Louise
L
Mendell
Nancy R
NR
Craddock
Nick
N
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Shaikh
Tamim H
TH
Susser
Ezra
E
Delisi
Lynn E
LE
Sullivan
Patrick F
PF
Deutsch
Curtis K
CK
Rapoport
Judith
J
Levy
Deborah L
DL
King
Mary-Claire
MC
Sebat
Jonathan
J
D002885:Chromosomes, Human, Pair 16; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006801:Humans; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics*