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A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome
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- Bonfiglio, F. (författare)
- Karolinska Institutet
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- Henstrom, M. (författare)
- Karolinska Institutet
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- Nag, A. (författare)
- Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
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- (creator_code:org_t)
- 2018-04-19
- 2018
- Engelska.
- Ingår i: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 30:9
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- IBS
- SNP
- genetics
- GWAS
- meta-analysis
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- ref (ämneskategori)
- art (ämneskategori)
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- Neurogastroenterology and Motility (Sök värdpublikationen i LIBRIS)
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- Av författaren/redakt...
- Bonfiglio, F.
- Henstrom, M.
- Nag, A.
- Hadizadeh, F.
- Zheng, T.
- Cenit, M. C.
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- Tigchelaar, E.
- Williams, F.
- Reznichenko, A.
- Ek, Weronica E.
- Rivera, N. V.
- Homuth, G.
- Aghdassi, A. A.
- Kacprowski, T.
- Mannikko, M.
- Karhunen, V.
- Bujanda, L.
- Rafter, J.
- Wijmenga, C.
- Ronkainen, J.
- Hysi, P.
- Zhernakova, A.
- D'Amato, M.
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- Karolinska Institutet
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