title: Loci nominally associated with autism from genome-wide analysis show enrichment of brain expression quantitative trait loci but not lymphoblastoid cell line expression quantitative trait loci.
abstract: BACKGROUND
  Autism spectrum disorder is a severe early onset neurodevelopmental disorder with high heritability but significant heterogeneity. Traditional genome-wide approaches to test for an association of common variants with autism susceptibility risk have met with limited success. However, novel methods to identify moderate risk alleles in attainable sample sizes are now gaining momentum.
  
  
  METHODS
  In this study, we utilized publically available genome-wide association study data from the Autism Genome Project and annotated the results (P <0.001) for expression quantitative trait loci present in the parietal lobe (GSE35977), cerebellum (GSE35974) and lymphoblastoid cell lines (GSE7761). We then performed a test of enrichment by comparing these results to simulated data conditioned on minor allele frequency to generate an empirical P-value indicating statistically significant enrichment of expression quantitative trait loci in top results from the autism genome-wide association study.
  
  
  RESULTS
  Our findings show a global enrichment of brain expression quantitative trait loci, but not lymphoblastoid cell line expression quantitative trait loci, among top single nucleotide polymorphisms from an autism genome-wide association study. Additionally, the data implicates individual genes SLC25A12, PANX1 and PANX2 as well as pathways previously implicated in autism.
  
  
  CONCLUSIONS
  These findings provide supportive rationale for the use of annotation-based approaches to genome-wide association studies.
authors.affiliation: Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. lea.k.davis@gmail.com.
authors.forename: Lea K
authors.initials: LK
authors.lastname: Davis
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gamazon
authors.forename: Emily
authors.initials: E
authors.lastname: Kistner-Griffin
authors.forename: Judith A
authors.initials: JA
authors.lastname: Badner
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: James S
authors.initials: JS
authors.lastname: Sutcliffe
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox