Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci
Background & aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profi...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/179935 |
| Acceso en línea: | https://hdl.handle.net/2445/179935 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Biòpsia Expressió gènica Còlon Biopsy Gene expression Colon (Anatomy) |
| _version_ | 1878737460968554496 |
|---|---|
| author | Diez Obrero, Virginia |
| author2 | Dampier, Christopher H. Moratalla Navarro, Ferran Devall, Matthew Plummer, Sarah J. Díez Villanueva, Anna Peters, Ulrike Bien, Stephanie Huyghe, Jeroen R. Kundaje, Anshul Ibáñez Sanz, Gemma Guinó, Elisabet Obón Santacana, Mireia Carreras Torres, Robert Casey, Graham Moreno Aguado, Víctor |
| author2_role | author author author author author author author author author author author author author author author |
| author_browse | Bien, Stephanie Carreras Torres, Robert Casey, Graham Dampier, Christopher H. Devall, Matthew Diez Obrero, Virginia Díez Villanueva, Anna Guinó, Elisabet Huyghe, Jeroen R. Ibáñez Sanz, Gemma Kundaje, Anshul Moratalla Navarro, Ferran Moreno Aguado, Víctor Obón Santacana, Mireia Peters, Ulrike Plummer, Sarah J. |
| author_facet | Diez Obrero, Virginia Dampier, Christopher H. Moratalla Navarro, Ferran Devall, Matthew Plummer, Sarah J. Díez Villanueva, Anna Peters, Ulrike Bien, Stephanie Huyghe, Jeroen R. Kundaje, Anshul Ibáñez Sanz, Gemma Guinó, Elisabet Obón Santacana, Mireia Carreras Torres, Robert Casey, Graham Moreno Aguado, Víctor |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| description | Background & aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource. Methods: We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses. Results: We provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application. Conclusions: We provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_a0285063251d7de61e2fd7d5fb158d0d |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/179935 |
| publishDate | 2021 |
| publishDateSort | 2021 |
| publisher | Elsevier BV |
| publisherStr | Elsevier BV |
| reponame_str | Dipòsit Digital de la UB |
| spelling | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci Diez Obrero, Virginia Dampier, Christopher H. Moratalla Navarro, Ferran Devall, Matthew Plummer, Sarah J. Díez Villanueva, Anna Peters, Ulrike Bien, Stephanie Huyghe, Jeroen R. Kundaje, Anshul Ibáñez Sanz, Gemma Guinó, Elisabet Obón Santacana, Mireia Carreras Torres, Robert Casey, Graham Moreno Aguado, Víctor Biòpsia Expressió gènica Còlon Biopsy Gene expression Colon (Anatomy) Background & aims: The association of genetic variation with tissue-specific gene expression and alternative splicing guides functional characterization of complex trait-associated loci and may suggest novel genes implicated in disease. Here, our aims were as follows: (1) to generate reference profiles of colon mucosa gene expression and alternative splicing and compare them across colon subsites (ascending, transverse, and descending), (2) to identify expression and splicing quantitative trait loci (QTLs), (3) to find traits for which identified QTLs contribute to single-nucleotide polymorphism (SNP)-based heritability, (4) to propose candidate effector genes, and (5) to provide a web-based visualization resource. Methods: We collected colonic mucosal biopsy specimens from 485 healthy adults and performed bulk RNA sequencing. We performed genome-wide SNP genotyping from blood leukocytes. Statistical approaches and bioinformatics software were used for QTL identification and downstream analyses. Results: We provided a complete quantification of gene expression and alternative splicing across colon subsites and described their differences. We identified thousands of expression and splicing QTLs and defined their enrichment at genome-wide regulatory regions. We found that part of the SNP-based heritability of diseases affecting colon tissue, such as colorectal cancer and inflammatory bowel disease, but also of diseases affecting other tissues, such as psychiatric conditions, can be explained by the identified QTLs. We provided candidate effector genes for multiple phenotypes. Finally, we provided the Colon Transcriptome Explorer web application. Conclusions: We provide a large characterization of gene expression and splicing across colon subsites. Our findings provide greater etiologic insight into complex traits and diseases influenced by transcriptomic changes in colon tissue. Elsevier BV https://hdl.handle.net/2445/179935 |
| spellingShingle | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci Diez Obrero, Virginia Biòpsia Expressió gènica Còlon Biopsy Gene expression Colon (Anatomy) |
| status_str | publishedVersion |
| title | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| title_full | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| title_fullStr | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| title_full_unstemmed | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| title_short | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| title_sort | Genetic Effects on Transcriptome Profiles in Colon Epithelium Provide Functional Insights for Genetic Risk Loci |
| topic | Biòpsia Expressió gènica Còlon Biopsy Gene expression Colon (Anatomy) |
| topic_facet | Biòpsia Expressió gènica Còlon Biopsy Gene expression Colon (Anatomy) |
| url | https://hdl.handle.net/2445/179935 |