Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
Background: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining t...
| Autores: | , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Servizo Galego de Saúde (SERGAS) |
| Repositorio: | RUNA. Repositorio da Consellería de Sanidade e Sergas |
| OAI Identifier: | oai:runa.sergas.gal:20.500.11940/21534 |
| Acceso en línea: | https://portalcientifico.sergas.gal//documentos/64609f7dc6d6be6c90fc6beb http://hdl.handle.net/20.500.11940/21534 |
| Access Level: | acceso abierto |
| Palabra clave: | Humans Irritable Bowel Syndrome Genome-Wide Association Study Anxiety Comorbidity Phenotype AS Pontevedra CHUP |
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Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variantsAlemany, S.Soler-Artigas, M.Cabana-Domínguez, J.Fakhreddine, D.Llonga, N.Vilar-Ribó, L.Rodríguez-Urrutia, A.Palacio, J.González Castro, Ana MaríaLobo, B.Alonso-Cotoner, C.Simrén, M.Santos, J.Ramos-Quiroga, J.A.Ribasés, M.HumansIrritable Bowel SyndromeGenome-Wide Association StudyAnxietyComorbidityPhenotypeAS PontevedraCHUPBackground: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. Methods: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. Results: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. Conclusions: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.This work was supported by the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR, 2017SGR-00444 and 2017SGR-1461); the Ministry of Science, Innovation and Universities (RYC2021-031324-I to J.C.D) and the European Union H2020 Programme (H2020/2014-2020) under grant agreements no. 848228 (DISCOvERIE). SA acknowledge a Miguel Servet contract (CP22/00026) awarded by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus, FSE +. M.S.A acknowledge a Miguel Servet contract (CP22/00128) awarded by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus, FSE +. This document is also an output of a project grant (Grant Agreement no: 848228, DISCOvERIE) funded under H2020 Research Programme of the European Commission. The content of this document represents the views of the author(s) only and is his/her/their sole responsibility; it cannot be considered to reflect the views of the European Commission or any other body of the European Union. The European Commission do not accept any responsibility for use that may be made of the information it contains.2023info:eu-repo/semantics/articlehttps://portalcientifico.sergas.gal//documentos/64609f7dc6d6be6c90fc6bebhttp://hdl.handle.net/20.500.11940/21534reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Ingléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/215342026-06-12T08:40:47Z |
| dc.title.none.fl_str_mv |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| title |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| spellingShingle |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants Alemany, S. Humans Irritable Bowel Syndrome Genome-Wide Association Study Anxiety Comorbidity Phenotype AS Pontevedra CHUP |
| title_short |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| title_full |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| title_fullStr |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| title_full_unstemmed |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| title_sort |
Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants |
| dc.creator.none.fl_str_mv |
Alemany, S. Soler-Artigas, M. Cabana-Domínguez, J. Fakhreddine, D. Llonga, N. Vilar-Ribó, L. Rodríguez-Urrutia, A. Palacio, J. González Castro, Ana María Lobo, B. Alonso-Cotoner, C. Simrén, M. Santos, J. Ramos-Quiroga, J.A. Ribasés, M. |
| author |
Alemany, S. |
| author_facet |
Alemany, S. Soler-Artigas, M. Cabana-Domínguez, J. Fakhreddine, D. Llonga, N. Vilar-Ribó, L. Rodríguez-Urrutia, A. Palacio, J. González Castro, Ana María Lobo, B. Alonso-Cotoner, C. Simrén, M. Santos, J. Ramos-Quiroga, J.A. Ribasés, M. |
| author_role |
author |
| author2 |
Soler-Artigas, M. Cabana-Domínguez, J. Fakhreddine, D. Llonga, N. Vilar-Ribó, L. Rodríguez-Urrutia, A. Palacio, J. González Castro, Ana María Lobo, B. Alonso-Cotoner, C. Simrén, M. Santos, J. Ramos-Quiroga, J.A. Ribasés, M. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Humans Irritable Bowel Syndrome Genome-Wide Association Study Anxiety Comorbidity Phenotype AS Pontevedra CHUP |
| topic |
Humans Irritable Bowel Syndrome Genome-Wide Association Study Anxiety Comorbidity Phenotype AS Pontevedra CHUP |
| description |
Background: Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. Methods: We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. Results: IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. Conclusions: These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders. |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://portalcientifico.sergas.gal//documentos/64609f7dc6d6be6c90fc6beb http://hdl.handle.net/20.500.11940/21534 |
| url |
https://portalcientifico.sergas.gal//documentos/64609f7dc6d6be6c90fc6beb http://hdl.handle.net/20.500.11940/21534 |
| 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 |
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http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas instname:Servizo Galego de Saúde (SERGAS) |
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Servizo Galego de Saúde (SERGAS) |
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RUNA. Repositorio da Consellería de Sanidade e Sergas |
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RUNA. Repositorio da Consellería de Sanidade e Sergas |
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