Visser, F.C.W. (2019) Interaction between genetic variants and tobacco smoking in Crohn’s disease and ulcerative colitis: a genome-wide analysis study. thesis, Medicine.
Full text available on request.Abstract
Background: Inflammatory Bowel Disease (IBD) is characterized by a complex etiology with an interplay between genetic, environmental, microbial, and immunologic factors. A divergent effect of tobacco smoke in two subtypes of IBD, Crohn’s Disease (CD) and Ulcerative Colitis (UC), supports the existence of gene-smoking interactions. Several genetic variants have already been found to interact with tobacco smoke in modifying the risk for IBD. However, gene-smoking interactions have previously been detected based on genome-wide Immunochipdata with a relatively poor coverage. We performed a case-only study in 1,097 patients, using over 12 million genetic variants with an excellent genome-wide content from Illumina Global Screening Array (GSA). We aimed to identify gene-smoking interactions that could potentially affect IBD, and to assess whether some of the interactions have an opposite effect in CD and UC. Methods: 12,130,010 single nucleotide polymorphisms (SNPs) from 1,097 IBD patients (500 CD patients and 402 UC patients) of known smoking status were available for genome-wide association studies (GWAS). Logistic regression analyses, adjusted for age and sex, were performed to compare groups with a different smoking status: ever vs never, current vs never, former vs never, and current vs never and former smokers. All analyses were performed in the total IBD cohort, and for CD and UC separately. Finally, meta-analysis of the CD results and UC results was done for each of the four smoking comparison groups. Results: 133 SNPs showed potential interaction with smoking in IBD (meta-analysis P < 5.0 x 10-5). 58 SNPs had a smoking-interaction odds ratio with an opposite direction in CD and UC (meta-analysis P < 5.0 x 10-5, and heterogeneity Cochrane Q test P < 0.05). We replicated one smoking-interacting locus that was previously identified in IBD: rs14458 (SYNPO, P = 6.04 x 10-6), and reported five SNPs that lie near known IBD genes (GCKR, PRKCB, SLC22A23, PDGFB, and CNTNAP2). Conclusion: We identified multiple novel gene-smoking interactions in IBD, of which 58 had an opposite effect in CD and UC. Our findings indicate a distinct effect of gene-smoking interactions on disease development of CD and UC, and provide a start for a better insight into the contribution of gene-smoking interactions to the etiology of IBD.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Festen |
| Faculty: | Medical Sciences |
| Date Deposited: | 02 Oct 2020 11:51 |
| Last Modified: | 02 Oct 2020 11:51 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2769 |
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