Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities
Background 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...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
BioMed Central
2016
|
| Online Access: | http://hdl.handle.net/1721.1/105756 https://orcid.org/0000-0002-6313-6357 https://orcid.org/0000-0002-2724-7228 |
| _version_ | 1826195791806464000 |
|---|---|
| author | Palmer, Nathan P. Kohane, Isaac S. Nazeen, Sumaiya Berger Leighton, Bonnie |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Palmer, Nathan P. Kohane, Isaac S. Nazeen, Sumaiya Berger Leighton, Bonnie |
| author_sort | Palmer, Nathan P. |
| collection | MIT |
| description | Background
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.
Results
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.
Conclusions
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.
Keywords
Autism spectrum disorder Co-morbidities of ASD Innate immunity pathways Three-tiered meta-analysis Gene expression |
| first_indexed | 2024-09-23T10:15:30Z |
| format | Article |
| id | mit-1721.1/105756 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:15:30Z |
| publishDate | 2016 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1057562022-09-26T16:50:14Z Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities Palmer, Nathan P. Kohane, Isaac S. Nazeen, Sumaiya Berger Leighton, Bonnie Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Nazeen, Sumaiya Berger Leighton, Bonnie Background 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. Results 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. Conclusions 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. Keywords Autism spectrum disorder Co-morbidities of ASD Innate immunity pathways Three-tiered meta-analysis Gene expression National Institutes of Health (U.S.) (grant GM081871) Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology United States. J. William Fulbright Foreign Scholarship Board (International Fulbright Science and Technology Fellowship) 2016-12-08T20:21:49Z 2016-12-08T20:21:49Z 2016-11 2016-07 2016-11-15T04:40:24Z Article http://purl.org/eprint/type/JournalArticle 1474-760X http://hdl.handle.net/1721.1/105756 Nazeen, Sumaiya et al. “Integrative Analysis of Genetic Data Sets Reveals a Shared Innate Immune Component in Autism Spectrum Disorder and Its Co-Morbidities.” Genome Biology 17.1 (2016): n. pag. https://orcid.org/0000-0002-6313-6357 https://orcid.org/0000-0002-2724-7228 en http://dx.doi.org/10.1186/s13059-016-1084-z Genome Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Palmer, Nathan P. Kohane, Isaac S. Nazeen, Sumaiya Berger Leighton, Bonnie Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title | Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title_full | Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title_fullStr | Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title_full_unstemmed | Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title_short | Integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co-morbidities |
| title_sort | integrative analysis of genetic data sets reveals a shared innate immune component in autism spectrum disorder and its co morbidities |
| url | http://hdl.handle.net/1721.1/105756 https://orcid.org/0000-0002-6313-6357 https://orcid.org/0000-0002-2724-7228 |
| work_keys_str_mv | AT palmernathanp integrativeanalysisofgeneticdatasetsrevealsasharedinnateimmunecomponentinautismspectrumdisorderanditscomorbidities AT kohaneisaacs integrativeanalysisofgeneticdatasetsrevealsasharedinnateimmunecomponentinautismspectrumdisorderanditscomorbidities AT nazeensumaiya integrativeanalysisofgeneticdatasetsrevealsasharedinnateimmunecomponentinautismspectrumdisorderanditscomorbidities AT bergerleightonbonnie integrativeanalysisofgeneticdatasetsrevealsasharedinnateimmunecomponentinautismspectrumdisorderanditscomorbidities |