Genetic associations on major depression: curation and functional analysis

Major depression (MD) is the leading cause of impairment worldwide. The lack of understanding of its biological underpinnings hampers the development of better diagnostic tools and treatments. Thanks to the advances in genetic association studies, multiple genetic variants significantly associated w...

Descripción completa

Detalles Bibliográficos
Autor: Pérez Granado, Judith
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/687887
Acceso en línea:http://hdl.handle.net/10803/687887
Access Level:acceso abierto
Palabra clave:Psychiatric disorders
Major depression
Functional genomics
Genome-wide association studies
Bioinformatics
Trastorns psiquiàtrics
Depressió major
Genòmica funcional
Estudis d’associació del genoma complet
Bioinformàtica
616.89
Descripción
Sumario:Major depression (MD) is the leading cause of impairment worldwide. The lack of understanding of its biological underpinnings hampers the development of better diagnostic tools and treatments. Thanks to the advances in genetic association studies, multiple genetic variants significantly associated with MD have been identified. In this thesis, we aim to leverage this knowledge to advance in the understanding of MD and unravel its molecular mechanisms. For that, we developed curation guidelines to evaluate available genetic association data on MD of diverse nature, and created an expert-curated database of genetic variants associated with MD. Then, we leveraged these data and functional genomic tools to unravel the role of these variants in disease pathogenesis and propose mechanistic hypotheses. In light of the plethora of tools available to perform such analyses, we conducted a benchmarking analysis to evaluate their performance and compare their outcomes; highlighting the need for guidelines for method selection and evaluation. Overall, this thesis contributes to filling the gap regarding the quality assessment of genetic studies on MD, and to advance in discovering the functional role of MD-associated variants by using in silico approaches.