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Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- Source :
- Nature Genetics, Nature genetics, 53(11), 1543-1552. Nature Publishing Group
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Funder: Kennedy Trust Rheumatology Research Prize Studentship<br />Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167)<br />Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772<br />Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL<br />Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421<br />Irritable bowel syndrome (IBS) results from disordered brain���gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain���gut interactions underlying IBS.
- Subjects :
- Male
Molecular Chaperone
Mood Disorder
631/208/205/2138
Biology
692/699/1503/1502/2071
Bioinformatics
Polymorphism, Single Nucleotide
Genetic pathways
38/43
Irritable Bowel Syndrome
Cytoskeletal Protein
Genetics
medicine
Genetic predisposition
Aged
Anxiety Disorders
CD56 Antigen
Cell Adhesion Molecules
Cytoskeletal Proteins
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Guanine Nucleotide Exchange Factors
Homeodomain Proteins
Humans
Middle Aged
Molecular Chaperones
Mood Disorders
United Kingdom
Polymorphism
692/699/476
Irritable bowel syndrome
Depression (differential diagnoses)
article
Homeodomain Protein
Single Nucleotide
Guanine Nucleotide Exchange Factor
medicine.disease
Neuroticism
Biobank
Mood
Cell Adhesion Molecule
Anxiety
medicine.symptom
Anxiety Disorder
Human
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 53
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....70d3e63ecdfa51d27cd4c008b5d1360d