uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome
Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, Donostia San Sebastian, Gipuzkoa, Spain; Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.
Show others and affiliations
2018 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 30, no 9, article id e13358Article in journal (Refereed) Published
Abstract [en]

BackgroundIrritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. MethodsBased on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Key ResultsSuggestive GWAS signals (P5.0x10(-6)) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P=3.1x10(-10)) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Conclusion & InferencesOur results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 30, no 9, article id e13358
Keywords [en]
IBS, SNP, genetics, GWAS, meta-analysis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:uu:diva-366264DOI: 10.1111/nmo.13358ISI: 000445193400013PubMedID: 29673008OAI: oai:DiVA.org:uu-366264DiVA, id: diva2:1264099
Funder
Swedish Research Council, VR 2013-3862Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2018-11-19Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Ek, Weronica E.

Search in DiVA

By author/editor
Ek, Weronica E.
By organisation
Medicinsk genetik och genomikScience for Life Laboratory, SciLifeLab
In the same journal
Neurogastroenterology and Motility
Gastroenterology and Hepatology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 222 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf