التفاصيل البيبلوغرافية
| العنوان: |
Disease similarity network analysis of Autism Spectrum Disorder and comorbid brain disorders. |
| المؤلفون: |
Vilela, Joana, Martiniano, Hugo, Marques, Ana Rita, Santos, João Xavier, Rasga, Célia, Oliveira, Guiomar, Moura Vicente, Astrid |
| المصدر: |
Frontiers in Molecular Neuroscience; 8/18/2022, Vol. 15, p1-13, 13p |
| مصطلحات موضوعية: |
AUTISM spectrum disorders, GENETIC disorders, COMMUNITIES, SPECTRUM analysis, SCHIZOPHRENIA, BRAIN diseases |
| مستخلص: |
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 diseaseassociated 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-offunction 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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