Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation, variable severity, and multiple comorbidities. A complex underlying genetic architecture matches the clinical heterogeneity, and evidence indicates that several co-occurring brain disorders shar...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.932305/full |
| _version_ | 1798039070484463616 |
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| author | Joana Vilela Joana Vilela Hugo Martiniano Hugo Martiniano Ana Rita Marques Ana Rita Marques João Xavier Santos João Xavier Santos Célia Rasga Célia Rasga Guiomar Oliveira Guiomar Oliveira Astrid Moura Vicente Astrid Moura Vicente |
| author_facet | Joana Vilela Joana Vilela Hugo Martiniano Hugo Martiniano Ana Rita Marques Ana Rita Marques João Xavier Santos João Xavier Santos Célia Rasga Célia Rasga Guiomar Oliveira Guiomar Oliveira Astrid Moura Vicente Astrid Moura Vicente |
| author_sort | Joana Vilela |
| collection | DOAJ |
| description | Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation, variable severity, and multiple comorbidities. A complex underlying genetic architecture matches the clinical heterogeneity, and evidence indicates that several co-occurring brain disorders share a genetic component with ASD. In this study, we established a genetic similarity disease network approach to explore the shared genetics between ASD and frequent comorbid brain diseases (and subtypes), namely Intellectual Disability, Attention-Deficit/Hyperactivity Disorder, and Epilepsy, as well as other rarely co-occurring neuropsychiatric conditions in the Schizophrenia and Bipolar Disease spectrum. Using sets of disease-associated genes curated by the DisGeNET database, disease genetic similarity was estimated from the Jaccard coefficient between disease pairs, and the Leiden detection algorithm was used to identify network disease communities and define shared biological pathways. We identified a heterogeneous brain disease community that is genetically more similar to ASD, and that includes Epilepsy, Bipolar Disorder, Attention-Deficit/Hyperactivity Disorder combined type, and some disorders in the Schizophrenia Spectrum. To identify loss-of-function rare de novo variants within shared genes underlying the disease communities, we analyzed a large ASD whole-genome sequencing dataset, showing that ASD shares genes with multiple brain disorders from other, less genetically similar, communities. Some genes (e.g., SHANK3, ASH1L, SCN2A, CHD2, and MECP2) were previously implicated in ASD and these disorders. This approach enabled further clarification of genetic sharing between ASD and brain disorders, with a finer granularity in disease classification and multi-level evidence from DisGeNET. Understanding genetic sharing across disorders has important implications for disease nosology, pathophysiology, and personalized treatment. |
| first_indexed | 2024-04-11T21:48:50Z |
| format | Article |
| id | doaj.art-b2ec72d7ed224cd79da47cc8cbdaa7f8 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-11T21:48:50Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-b2ec72d7ed224cd79da47cc8cbdaa7f82022-12-22T04:01:18ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-08-011510.3389/fnmol.2022.932305932305Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disordersJoana Vilela0Joana Vilela1Hugo Martiniano2Hugo Martiniano3Ana Rita Marques4Ana Rita Marques5João Xavier Santos6João Xavier Santos7Célia Rasga8Célia Rasga9Guiomar Oliveira10Guiomar Oliveira11Astrid Moura Vicente12Astrid Moura Vicente13Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalDepartamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalDepartamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalDepartamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalDepartamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalUnidade de Neurodesenvolvimento e Autismo, Serviço do Centro de Desenvolvimento da Criança, Centro de Investigação e Formação Clínica, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, PortugalFaculty of Medicine, University Clinic of Pediatrics and Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, Coimbra, PortugalDepartamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, PortugalFaculty of Sciences, BioISI-Biosystems & Integrative Sciences Institute, University of Lisboa, Lisbon, PortugalAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder with heterogeneous clinical presentation, variable severity, and multiple comorbidities. A complex underlying genetic architecture matches the clinical heterogeneity, and evidence indicates that several co-occurring brain disorders share a genetic component with ASD. In this study, we established a genetic similarity disease network approach to explore the shared genetics between ASD and frequent comorbid brain diseases (and subtypes), namely Intellectual Disability, Attention-Deficit/Hyperactivity Disorder, and Epilepsy, as well as other rarely co-occurring neuropsychiatric conditions in the Schizophrenia and Bipolar Disease spectrum. Using sets of disease-associated genes curated by the DisGeNET database, disease genetic similarity was estimated from the Jaccard coefficient between disease pairs, and the Leiden detection algorithm was used to identify network disease communities and define shared biological pathways. We identified a heterogeneous brain disease community that is genetically more similar to ASD, and that includes Epilepsy, Bipolar Disorder, Attention-Deficit/Hyperactivity Disorder combined type, and some disorders in the Schizophrenia Spectrum. To identify loss-of-function rare de novo variants within shared genes underlying the disease communities, we analyzed a large ASD whole-genome sequencing dataset, showing that ASD shares genes with multiple brain disorders from other, less genetically similar, communities. Some genes (e.g., SHANK3, ASH1L, SCN2A, CHD2, and MECP2) were previously implicated in ASD and these disorders. This approach enabled further clarification of genetic sharing between ASD and brain disorders, with a finer granularity in disease classification and multi-level evidence from DisGeNET. Understanding genetic sharing across disorders has important implications for disease nosology, pathophysiology, and personalized treatment.https://www.frontiersin.org/articles/10.3389/fnmol.2022.932305/fullAutism Spectrum Disorder (ASD)Psychiatric geneticscross-disorder geneticsbrain disordersdisease similaritynetwork analysis |
| spellingShingle | Joana Vilela Joana Vilela Hugo Martiniano Hugo Martiniano Ana Rita Marques Ana Rita Marques João Xavier Santos João Xavier Santos Célia Rasga Célia Rasga Guiomar Oliveira Guiomar Oliveira Astrid Moura Vicente Astrid Moura Vicente Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders Frontiers in Molecular Neuroscience Autism Spectrum Disorder (ASD) Psychiatric genetics cross-disorder genetics brain disorders disease similarity network analysis |
| title | Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders |
| title_full | Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders |
| title_fullStr | Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders |
| title_full_unstemmed | Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders |
| title_short | Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders |
| title_sort | disease similarity network analysis of autism spectrum disorder and comorbid brain disorders |
| topic | Autism Spectrum Disorder (ASD) Psychiatric genetics cross-disorder genetics brain disorders disease similarity network analysis |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.932305/full |
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