title: Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities.
abstract: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder that tends to co-occur with other diseases, including asthma, inflammatory bowel disease, infections, cerebral palsy, dilated cardiomyopathy, muscular dystrophy, and schizophrenia. However, the molecular basis of this co-occurrence, and whether it is due to a shared component that influences both pathophysiology and environmental triggering of illness, has not been elucidated. To address this, we deploy a three-tiered transcriptomic meta-analysis that functions at the gene, pathway, and disease levels across ASD and its co-morbidities.
  
  
  
  Our analysis reveals a novel shared innate immune component between ASD and all but three of its co-morbidities that were examined. In particular, we find that the Toll-like receptor signaling and the chemokine signaling pathways, which are key pathways in the innate immune response, have the highest shared statistical significance. Moreover, the disease genes that overlap these two innate immunity pathways can be used to classify the cases of ASD and its co-morbidities vs. controls with at least 70 % accuracy.
  
  
  
  This finding suggests that a neuropsychiatric condition and the majority of its non-brain-related co-morbidities share a dysregulated signal that serves as not only a common genetic basis for the diseases but also as a link to environmental triggers. It also raises the possibility that treatment and/or prophylaxis used for disorders of innate immunity may be successfully used for ASD patients with immune-related phenotypes.
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, MA, USA.
authors.forename: Sumaiya
authors.initials: S
authors.lastname: Nazeen
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, 25 Shattuck Street, Boston, 02115, MA, USA.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Palmer
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, MA, USA. bab@mit.edu.|Department of Mathematics, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, MA, USA. bab@mit.edu.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Berger
authors.affiliation: Department of Biomedical Informatics, Harvard Medical School, 25 Shattuck Street, Boston, 02115, MA, USA. isaac_kohane@harvard.edu.
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
mesh_terms: D000067877:Autism Spectrum Disorder / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015897:Comorbidity; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics* / Q000276:immunology
keywords: Autism spectrum disorder; Co-morbidities of ASD; Gene expression; Innate immunity pathways; Three-tiered meta-analysis