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Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Flow charts for the selection of eligible genetic and epigenetic studies.
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f1: Flow charts for the selection of eligible genetic and epigenetic studies.

Mentions: A total of 3,137 citations were identified. After title and abstract review, 1,208 publications were reviewed in full text; 84 publications were finally included, 79 of which were on paediatric CD, 34 on paediatric UC and 5 on paediatric IBD (Fig. 1). Characteristics of the included studies are presented in Supplementary Table S2. Of these, the majority of the studies (n = 57, 67.9%) were conducted in pediatric or early-onset IBD patients younger than 17 years, while 10 studies (11.9%) focused on IBD patients below 16 years and 17 studies (20.2%) focused on IBD patients below 18 years. The geographic distribution of the study populations (Supplementary Fig. S1) suggests a lack of population diversity in exploring the genetic factors of paediatric IBD, since more than 90% of the studies (n = 78) were conducted among white populations and only a small number of studies were conducted in Asian (n = 6, 7.6%) and African American (n = 1, 1.3%).


Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease
Flow charts for the selection of eligible genetic and epigenetic studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037432&req=5

f1: Flow charts for the selection of eligible genetic and epigenetic studies.
Mentions: A total of 3,137 citations were identified. After title and abstract review, 1,208 publications were reviewed in full text; 84 publications were finally included, 79 of which were on paediatric CD, 34 on paediatric UC and 5 on paediatric IBD (Fig. 1). Characteristics of the included studies are presented in Supplementary Table S2. Of these, the majority of the studies (n = 57, 67.9%) were conducted in pediatric or early-onset IBD patients younger than 17 years, while 10 studies (11.9%) focused on IBD patients below 16 years and 17 studies (20.2%) focused on IBD patients below 18 years. The geographic distribution of the study populations (Supplementary Fig. S1) suggests a lack of population diversity in exploring the genetic factors of paediatric IBD, since more than 90% of the studies (n = 78) were conducted among white populations and only a small number of studies were conducted in Asian (n = 6, 7.6%) and African American (n = 1, 1.3%).

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.