title: Common genetic variants on 5p14.1 associate with autism spectrum disorders.
abstract: 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.
authors.affiliation: Center for Applied Genomics, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Deqiong
authors.initials: D
authors.lastname: Ma
authors.forename: Maja
authors.initials: M
authors.lastname: Bucan
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Brett S
authors.initials: BS
authors.lastname: Abrahams
authors.forename: Daria
authors.initials: D
authors.lastname: Salyakina
authors.forename: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Patrick M A
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.forename: Edward
authors.initials: E
authors.lastname: Frackelton
authors.forename: Rosetta
authors.initials: R
authors.lastname: Chiavacci
authors.forename: Nagahide
authors.initials: N
authors.lastname: Takahashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Eric
authors.initials: E
authors.lastname: Rappaport
authors.forename: Clara M
authors.initials: CM
authors.lastname: Lajonchere
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Munson
authors.forename: Annette
authors.initials: A
authors.lastname: Estes
authors.forename: Olena
authors.initials: O
authors.lastname: Korvatska
authors.forename: Joseph
authors.initials: J
authors.lastname: Piven
authors.forename: Lisa I
authors.initials: LI
authors.lastname: Sonnenblick
authors.forename: Ana I
authors.initials: AI
authors.lastname: Alvarez Retuerto
authors.forename: Edward I
authors.initials: EI
authors.lastname: Herman
authors.forename: Hongmei
authors.initials: H
authors.lastname: Dong
authors.forename: Ted
authors.initials: T
authors.lastname: Hutman
authors.forename: Marian
authors.initials: M
authors.lastname: Sigman
authors.forename: Sally
authors.initials: S
authors.lastname: Ozonoff
authors.forename: Ami
authors.initials: A
authors.lastname: Klin
authors.forename: Thomas
authors.initials: T
authors.lastname: Owley
authors.forename: John A
authors.initials: JA
authors.lastname: Sweeney
authors.forename: Camille W
authors.initials: CW
authors.lastname: Brune
authors.forename: Rita M
authors.initials: RM
authors.lastname: Cantor
authors.forename: Raphael
authors.initials: R
authors.lastname: Bernier
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.forename: William M
authors.initials: WM
authors.lastname: McMahon
authors.forename: Judith
authors.initials: J
authors.lastname: Miller
authors.forename: Matthew W
authors.initials: MW
authors.lastname: State
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Wassink
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.forename: Susan E
authors.initials: SE
authors.lastname: Levy
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schultz
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: James S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Minshew
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: Geraldine
authors.initials: G
authors.lastname: Dawson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: 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
chemical_list: C107751:CDH10 protein, human; C430712:CDH9 protein, human; D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D005819:Genetic Markers