Investigation of maternal genotype effects in autism by genome-wide association

Autism Res. 2014 Apr;7(2):245-53. doi: 10.1002/aur.1363. Epub 2014 Feb 25.


Like most psychiatric disorders, autism spectrum disorders have both a genetic and an environmental component. While previous studies have clearly demonstrated the contribution of in utero (prenatal) environment on autism risk, most of them focused on transient environmental factors. Based on a recent sibling study, we hypothesized that environmental factors could also come from the maternal genome, which would result in persistent effects across siblings. In this study, the possibility of maternal genotype effects was examined by looking for common variants (single-nucleotide polymorphisms or SNPs) in the maternal genome associated with increased risk of autism in children. A case/control genome-wide association study was performed using mothers of probands as cases, and either fathers of probands or normal females as controls. Autism Genetic Resource Exchange and Illumina Genotype Control Database were used as our discovery cohort (n = 1616). The same analysis was then replicated on Simon Simplex Collection and Study of Addiction: Genetics and Environment datasets (n = 2732). We did not identify any SNP that reached genome-wide significance (P < 10(-8) ), and thus a common variant of large effect is unlikely. However, there was evidence for the possibility of a large number of alleles of effective size marginally below our power to detect.

Keywords: AGRE; GWAS; SSC; autism; maternal genotype effect.

Publication types

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

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Child
  • Child Development Disorders, Pervasive / genetics*
  • Chromosomes, Human, Pair 6 / genetics
  • Female
  • Gene Frequency
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study*
  • Genotype*
  • Humans
  • Logistic Models
  • Male
  • Mothers*
  • Polymorphism, Single Nucleotide / genetics
  • Risk
  • Utrophin / genetics


  • UTRN protein, human
  • Utrophin