Common genetic variants on 5p14.1 associate with autism spectrum disorders.
Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
Wang
Kai
K
Center for Applied Genomics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Zhang
Haitao
H
Ma
Deqiong
D
Bucan
Maja
M
Glessner
Joseph T
JT
Abrahams
Brett S
BS
Salyakina
Daria
D
Imielinski
Marcin
M
Bradfield
Jonathan P
JP
Sleiman
Patrick M A
PM
Kim
Cecilia E
CE
Hou
Cuiping
C
Frackelton
Edward
E
Chiavacci
Rosetta
R
Takahashi
Nagahide
N
Sakurai
Takeshi
T
Rappaport
Eric
E
Lajonchere
Clara M
CM
Munson
Jeffrey
J
Estes
Annette
A
Korvatska
Olena
O
Piven
Joseph
J
Sonnenblick
Lisa I
LI
Alvarez Retuerto
Ana I
AI
Herman
Edward I
EI
Dong
Hongmei
H
Hutman
Ted
T
Sigman
Marian
M
Ozonoff
Sally
S
Klin
Ami
A
Owley
Thomas
T
Sweeney
John A
JA
Brune
Camille W
CW
Cantor
Rita M
RM
Bernier
Raphael
R
Gilbert
John R
JR
Cuccaro
Michael L
ML
McMahon
William M
WM
Miller
Judith
J
State
Matthew W
MW
Wassink
Thomas H
TH
Coon
Hilary
H
Levy
Susan E
SE
Schultz
Robert T
RT
Nurnberger
John I
JI
Haines
Jonathan L
JL
Sutcliffe
James S
JS
Cook
Edwin H
EH
Minshew
Nancy J
NJ
Buxbaum
Joseph D
JD
Dawson
Geraldine
G
Grant
Struan F A
SF
Geschwind
Daniel H
DH
Pericak-Vance
Margaret A
MA
Schellenberg
Gerard D
GD
Hakonarson
Hakon
H
D001321:Autistic Disorder / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015331:Cohort Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results
C107751:CDH10 protein, human; C430712:CDH9 protein, human; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers