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