Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
Abstract 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 expl...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-04-01
|
| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04107-5 |
| _version_ | 1797840895558549504 |
|---|---|
| author | Silvia Alemany María Soler-Artigas Judit Cabana-Domínguez Dana Fakhreddine Natalia Llonga Laura Vilar-Ribó Amanda Rodríguez-Urrutia Judit Palacio Ana María González-Castro Beatriz Lobo Carmen Alonso-Cotoner Magnus Simrén Javier Santos Josep Antoni Ramos-Quiroga Marta Ribasés |
| author_facet | Silvia Alemany María Soler-Artigas Judit Cabana-Domínguez Dana Fakhreddine Natalia Llonga Laura Vilar-Ribó Amanda Rodríguez-Urrutia Judit Palacio Ana María González-Castro Beatriz Lobo Carmen Alonso-Cotoner Magnus Simrén Javier Santos Josep Antoni Ramos-Quiroga Marta Ribasés |
| author_sort | Silvia Alemany |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T16:22:12Z |
| format | Article |
| id | doaj.art-facbd6f19650446a9205f35254e837f7 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T16:22:12Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-facbd6f19650446a9205f35254e837f72023-04-23T11:26:43ZengBMCJournal of Translational Medicine1479-58762023-04-0121111610.1186/s12967-023-04107-5Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variantsSilvia Alemany0María Soler-Artigas1Judit Cabana-Domínguez2Dana Fakhreddine3Natalia Llonga4Laura Vilar-Ribó5Amanda Rodríguez-Urrutia6Judit Palacio7Ana María González-Castro8Beatriz Lobo9Carmen Alonso-Cotoner10Magnus Simrén11Javier Santos12Josep Antoni Ramos-Quiroga13Marta Ribasés14Psychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaDepartment of Mental Health, Hospital Universitari Vall d’HebronLaboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLaboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariLaboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of GothenburgLaboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital UniversitariPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaPsychiatric Genetics Unit, Group of Psychiatry Mental Health and Addiction, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaAbstract 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.https://doi.org/10.1186/s12967-023-04107-5Irritable bowel syndrome (IBS)NeuroticismDepressionAnxietyMulti-trait genome-wide association study (MTAG) |
| spellingShingle | Silvia Alemany María Soler-Artigas Judit Cabana-Domínguez Dana Fakhreddine Natalia Llonga Laura Vilar-Ribó Amanda Rodríguez-Urrutia Judit Palacio Ana María González-Castro Beatriz Lobo Carmen Alonso-Cotoner Magnus Simrén Javier Santos Josep Antoni Ramos-Quiroga Marta Ribasés Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants Journal of Translational Medicine Irritable bowel syndrome (IBS) Neuroticism Depression Anxiety Multi-trait genome-wide association study (MTAG) |
| title | 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_short | 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 |
| topic | Irritable bowel syndrome (IBS) Neuroticism Depression Anxiety Multi-trait genome-wide association study (MTAG) |
| url | https://doi.org/10.1186/s12967-023-04107-5 |
| work_keys_str_mv | AT silviaalemany genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT mariasolerartigas genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT juditcabanadominguez genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT danafakhreddine genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT nataliallonga genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT lauravilarribo genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT amandarodriguezurrutia genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT juditpalacio genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT anamariagonzalezcastro genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT beatrizlobo genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT carmenalonsocotoner genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT magnussimren genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT javiersantos genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT josepantoniramosquiroga genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants AT martaribases genomewidemultitraitanalysisofirritablebowelsyndromeandrelatedmentalconditionsidentifies38newindependentvariants |