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

Abstract

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

Down-Regulation
Gene Expression
Genes
Genetic Markers
Genome
Computer Software
Up-Regulation (Physiology)
Adaptation
Fetal Brain
Genetic Loci

Related Feeds

Autism: Treatment Targets

The absence of effective treatments for autism are due to the high clinical and genetic heterogeneity between affected individuals, restricted knowledge of the underlying pathophysiological mechanisms, and the lack of reliable diagnostic biomarkers. Identification of more homogenous biological subgroups is therefore essential for the development of novel treatments based on the molecular mechanisms underpinning autism and autism spectrum disorders. Find the latest research on autism treatment targets here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research on autism.