Evidence that duplications of 22q11.2 protect against schizophrenia.
A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk-inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
E
E
Rees
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
G
G
Kirov
1] Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA [2] Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, IL, USA.
A
A
Sanders
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
J T R
JT
Walters
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
K D
KD
Chambert
Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
J
J
Shi
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
J
J
Szatkiewicz
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
C
C
O'Dushlaine
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
A L
AL
Richards
1] MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK [2] School of Biomedical and Biological Sciences, Plymouth University, Plymouth, UK.
E K
EK
Green
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
I
I
Jones
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
G
G
Davies
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
S E
SE
Legge
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
J L
JL
Moran
Department of Psychiatry and Behavioral Science, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA.
C
C
Pato
Department of Psychiatry and Behavioral Science, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA.
M
M
Pato
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
G
G
Genovese
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
D
D
Levinson
1] Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA [2] Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, IL, USA.
J
J
Duan
Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA.
W
W
Moy
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
H H H
HH
Göring
Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
D
D
Morris
Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
P
P
Cormican
Department of Psychiatry and Human Genetics, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
K S
KS
Kendler
Department of Psychiatry, Queen's University, Belfast, Northern Ireland.
F A
FA
O'Neill
Department of Psychiatry and Human Genetics, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
B
B
Riley
Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
M
M
Gill
Department of Psychiatry and Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin 2, Ireland.
A
A
Corvin
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
N
N
Craddock
Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
P
P
Sklar
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
C
C
Hultman
1] Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden [3] Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
P F
PF
Sullivan
1] Department of Psychiatry and Behavioral Sciences, NorthShore University HealthSystem, Evanston, IL, USA [2] Department of Psychiatry and Behavioral Sciences, University of Chicago, Chicago, IL, USA.
P V
PV
Gejman
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA, USA.
S A
SA
McCarroll
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
M C
MC
O'Donovan
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
M J
MJ
Owen
D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics*; D058674:Chromosome Duplication / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*