DOI: 10.1101/480624Nov 29, 2018Paper

Novel Insight into the Aetiology of Autism Spectrum Disorder Gained by Integrating Expression Data with Genome-wide Association Statistics

BioRxiv : the Preprint Server for Biology
Oliver PainRichard J L Anney


Background: A recent genome-wide association study (GWAS) of autism spectrum disorders (ASD) (Ncases=18,381, Ncontrols=27,969) has provided novel opportunities for investigating the aetiology of ASD. Here, we integrate the ASD GWAS summary statistics with summary-level gene expression data to infer differential gene expression in ASD, an approach called transcriptome-wide association study (TWAS). Methods: Using FUSION software, ASD GWAS summary statistics were integrated with predictors of gene expression from 16 human datasets, including adult and fetal brain. A novel adaptation of established statistical methods was then used to test for enrichment within candidate pathways, specific tissues, and at different stages of brain development. The proportion of ASD heritability explained by predicted expression of genes in the TWAS was estimated using stratified linkage disequilibrium-score regression. Results: This study identified 14 genes as significantly differentially expressed in ASD, 13 of which were outside of known genome-wide significant loci (+/-500kb). XRN2, a gene proximal to an ASD GWAS locus, was inferred to be significantly upregulated in ASD, providing insight into functional consequence of this associated locus. ...Continue Reading

Related Concepts

Gene Expression
Genetic Markers
Computer Software
Up-Regulation (Physiology)
Fetal Brain
Genetic Loci

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