Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease.
We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn's disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols.
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Xue
X
Li
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Peige
P
Song
Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit Western General Hospital Edinburgh, Edinburgh, United Kingdom.
Maria
M
Timofeeva
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Xiangrui
X
Meng
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Igor
I
Rudan
School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada.
Julian
J
Little
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh and Western General Hospital Edinburgh, Edinburgh, United Kingdom.
Jack
J
Satsangi
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Harry
H
Campbell
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Evropi
E
Theodoratou
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