Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined ‐samples mega‐analysis

Blood‐based microarray studies comparing individuals affected with autism spectrum disorder (ASD) and typically developing individuals help characterize differences in circulating immune cell functions and offer potential biomarker signal. We sought to combine the subject‐level data from previously published studies by mega‐analysis to increase the statistical power. We identified studies that compared ex vivo blood or lymphocytes from ASD‐affected individuals and unrelated comparison subjects using Affymetrix or Illumina array platforms. Raw microarray data and clinical meta‐data were obtained from seven studies, totaling 626 affected and 447 comparison subjects. Microarray data were processed using uniform methods. Covariate‐controlled mixed‐effect linear models were used to identify gene transcripts and co‐expression network modules that were significantly associated with diagnostic status. Permutation‐based gene‐set analysis was used to identify functionally related sets of genes that were over‐ and under‐expressed among ASD samples. Our results were consistent with diminished interferon‐, EGF‐, PDGF‐, PI3K‐AKT‐mTOR‐, and RAS‐MAPK‐signaling cascades, and increased ribosomal translation and NK‐cell related activity in ASD. We explored evidence for sex‐differences in the ASD‐related transcriptomic signature. We also demonstrated that machine‐learning classifiers using blood transcriptome data perform with moderate accuracy whe...
Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - Category: Genetics & Stem Cells Authors: Tags: Rapid Publication Source Type: research