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...
| Autor: | |
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| Tipo de documento: | tese |
| Estado: | Versão publicada |
| Data de publicação: | 2023 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositório: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/687887 |
| Acesso em linha: | http://hdl.handle.net/10803/687887 |
| Access Level: | Acceso aberto |
| Palavra-chave: | 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 |
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Genetic associations on major depression: curation and functional analysisPérez Granado, JudithPsychiatric disordersMajor depressionFunctional genomicsGenome-wide association studiesBioinformaticsTrastorns psiquiàtricsDepressió majorGenòmica funcionalEstudis d’associació del genoma completBioinformàtica616.89Major 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.La depressió major (DM) és la principal causa d'incapacitat en tot el món. La falta de comprensió dels seus fonaments biològics dificulta el desenvolupament de millors diagnòstics i tractaments. Gràcies als avanços en estudis d'associació genètica, s'han identificat múltiples variants genètiques significativament associades a la DM. En aquesta tesi, volem aprofitar aquests coneixements per avançar en la comprensió de la DM i descobrir els seus mecanismes moleculars. Per a això, hem desenvolupat unes directrius de curació per avaluar l'ampli ventall de dades d'associació genètica disponibles sobre la DM i hem creat una base de dades de variants genètiques associades a la DM que ha estat curada per experts. Un cop finalitzada, vam aprofitar aquestes dades i diverses eines de genòmica funcional per entendre el paper d'aquestes variants en la patogènesi de la malaltia i proposar hipòtesis mecanístiques. Davant de la plètora d'eines disponibles, vam dur a terme una anàlisi de referència per avaluar el seu funcionament i comparar els seus resultats, on destaquem la necessitat de directrius per seleccionar I avaluar els mètodes. Globalment, aquesta tesi contribueix a omplir el buit que existeix pel que fa a l'avaluació de la qualitat dels estudis genètics sobre la DM, I avançar en el descobriment del paper functional de les variants associades a la DM mitjçant l’ús de mètodes in silico.Programa de doctorat en BiomedicinaUniversitat Pompeu FabraPiñero, JanetFurlong, Laura I.Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida202320232023info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion151 p.application/pdfhttp://hdl.handle.net/10803/687887TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésL'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/6878872026-06-14T12:46:07Z |
| dc.title.none.fl_str_mv |
Genetic associations on major depression: curation and functional analysis |
| title |
Genetic associations on major depression: curation and functional analysis |
| spellingShingle |
Genetic associations on major depression: curation and functional analysis Pérez Granado, Judith 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 |
| title_short |
Genetic associations on major depression: curation and functional analysis |
| title_full |
Genetic associations on major depression: curation and functional analysis |
| title_fullStr |
Genetic associations on major depression: curation and functional analysis |
| title_full_unstemmed |
Genetic associations on major depression: curation and functional analysis |
| title_sort |
Genetic associations on major depression: curation and functional analysis |
| dc.creator.none.fl_str_mv |
Pérez Granado, Judith |
| author |
Pérez Granado, Judith |
| author_facet |
Pérez Granado, Judith |
| author_role |
author |
| dc.contributor.none.fl_str_mv |
Piñero, Janet Furlong, Laura I. Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida |
| dc.subject.none.fl_str_mv |
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 |
| topic |
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 |
| description |
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. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 2023 2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/publishedVersion |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10803/687887 |
| url |
http://hdl.handle.net/10803/687887 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
http://creativecommons.org/licenses/by/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
151 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| publisher.none.fl_str_mv |
Universitat Pompeu Fabra |
| dc.source.none.fl_str_mv |
TDX (Tesis Doctorals en Xarxa) reponame:TDR. Tesis Doctorales en Red instname:CBUC, CESCA |
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CBUC, CESCA |
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TDR. Tesis Doctorales en Red |
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TDR. Tesis Doctorales en Red |
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15,301603 |