Common genetic variants on 5p14.1 associate with autism spectrum disorders

Nature. 2009 May 28;459(7246):528-33. doi: 10.1038/nature07999. Epub 2009 Apr 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autistic Disorder / genetics*
  • Brain / metabolism
  • Cadherins / genetics
  • Case-Control Studies
  • Cell Adhesion / genetics
  • Cell Adhesion Molecules, Neuronal / genetics
  • Chromosomes, Human, Pair 5 / genetics*
  • Cohort Studies
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results

Substances

  • CDH10 protein, human
  • CDH9 protein, human
  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Genetic Markers

Grant support