A Comprehensive multiomics approach towards understanding obsessive-compulsive disorder
To date, very little progress has been made towards elucidating the genetic causes of obsessive-compulsive disorder (OCD). In this project we have performed rare variant association study (RVAS) transcriptomics and metagenomics analyses to focus on areas relatively underexplored in OCD. We have iden...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/665800 |
| Acceso en línea: | http://hdl.handle.net/10803/665800 |
| Access Level: | acceso abierto |
| Palabra clave: | OCD Genomics Transcriptomics Metagenomics TOC Genòmica Transcriptòmica Metagenòmica 575 |
| Sumario: | To date, very little progress has been made towards elucidating the genetic causes of obsessive-compulsive disorder (OCD). In this project we have performed rare variant association study (RVAS) transcriptomics and metagenomics analyses to focus on areas relatively underexplored in OCD. We have identified and replicated an enrichment of rare variants in TMEM63A, a gene that encodes for a calcium-permeable cation channel, through whole-exome sequencing, RVAS and targeted resequencing analyses. Moreover, we have observed an overrepresentation of genes enriched in rare variants in OCD cases related to calcium signalling. Transcriptomic studies have identified differential expression of genes involved in neuronal development and function in OCD patients. Integration of our RVAS and transcriptomic results also uncover a possible role of semaphorins and axon guidance in OCD. Finally, metagenomics studies have confirmed the previously reported increase of the Rikenellaceae bacterial family in the gut microbiome and have shown a significant higher Actinobacteria/Fusobacteria ratio in the oro-pharyngeal microbiome of OCD cases. Our results actively encourage further research in these areas. |
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