title: Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism.
abstract: Recent studies of genomic variation associated with autism have suggested the existence of extreme heterogeneity. Large-scale transcriptomics should complement these results to identify core molecular pathways underlying autism. Here we report results from a large-scale RNA sequencing effort, utilizing region-matched autism and control brains to identify neuronal and microglial genes robustly dysregulated in autism cortical brain. Remarkably, we note that a gene expression module corresponding to M2-activation states in microglia is negatively correlated with a differentially expressed neuronal module, implicating dysregulated microglial responses in concert with altered neuronal activity-dependent genes in autism brains. These observations provide pathways and candidate genes that highlight the interplay between innate immunity and neuronal activity in the aetiology of autism.
authors.affiliation: Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Ellis
authors.affiliation: Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Foram N
authors.initials: FN
authors.lastname: Ashar
authors.affiliation: Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Moes
authors.affiliation: 1] Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2] Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bader
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Jianan
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: West
authors.affiliation: Department of Medicine, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking