Epidemiology of inflammatory bowel disease in a German twin cohort: Results of a nationwide study

Spehlmann, Martina E.; Begun, Alexander; Burghardt, Jens; Lepage, Patricia; Raedler, Andreas; Schreiber, Stefan

doi:10.1002/ibd.20380

Cited by 147 publications

(85 citation statements)

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“…The primacy of environmental risk factors in the development of IBD is demonstrated in twin studies. The concordance rate for ulcerative colitis (UC) is less than 20 % and is around 50 % for Crohn's disease (CD) in monozygotic twins [2][3][4]. Of note, twin studies have not provided much support for a host genetic influence on the gut microbiota [5].…”

Section: The Gut Microbiota: the Proximate Environmental Risk Factor mentioning

confidence: 99%

The microbiota in inflammatory bowel disease

2015

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This review explores our current understanding of the complex interaction between environmental risk factors, genetic traits and the development of inflammatory bowel disease. The primacy of environmental risk factors is illustrated by the rapid increase in the incidence of the disease worldwide. We discuss how the gut microbiota is the proximate environmental risk factor for subsequent development of inflammatory bowel disease. The evolving fields of virome and mycobiome studies will further our understanding of the full potential of the gut microbiota in disease pathogenesis. Manipulating the gut microbiota is a promising therapeutic avenue.

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Section: The Gut Microbiota: the Proximate Environmental Risk Factor mentioning

confidence: 99%

The microbiota in inflammatory bowel disease

2015

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“…Except for highly penetrant Mendelian disorders, MZ twins exhibit a broad range (25%-95%) of disease discordance for most complex diseases that cannot be explained by classical genetics (Nance 1977). A recent report showed a discordance rate of 84% in MZ twins for UC (Spehlmann et al 2008). While, historically, twin-based studies have been employed for the identification of disease genes, recent interest in MZ twin studies has moved to mapping epigenetic changes in identical genomes that have precipitated into different phenotypes (Fraga et al 2005;Kaminsky et al 2009;Javierre et al 2010;Rakyan et al 2011a).…”

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confidence: 99%

A functional methylome map of ulcerative colitis

et al. 2012

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The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation.

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“…A study done in German 9 showed that 35% of monozygotic pairs, but only 3% of dizygotic pairs, were concordant for the disorder. In 70% of discordant monozygotic pairs the first-born had IBD.…”

Section: Geneticsmentioning

confidence: 99%

“…In 70% of discordant monozygotic pairs the first-born had IBD. 9 Substantial phenotypic (location, behaviour, and age at diagnosis) concordance exists, both at diagnosis and longitudinally, in monozygotic twins. 10 Familial aggregation is confirmed.…”

Section: Geneticsmentioning

confidence: 99%

Pathology of Inflammatory Bowel Disease

2015

J Pathol Nep

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Inflammatory bowel disease is a group of inflammatory disorders of unknown etiology. Various genetic factors, mucosal immune response, inappropriate activation of immune system driven by the presence of various luminal flora and epithelial defects have been postulated. Crohn disease and Ulcerative colitis are the two most common inflammatory bowel diseases. Since, specific clinical laboratory features are lacking which may help in establishing a diagnosis histopathological diagnosis remains the gold standard. This review highlights the known hypothesis regarding the etiopathogenesis of these two diseases and also describes pertinent histological features.Journal of Pathology of Nepal (2015) Vol. 5, 756-765

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Epidemiology of inflammatory bowel disease in a German twin cohort: Results of a nationwide study

Abstract: This study confirms a stronger genetic influence in CD than in UC. The high preponderance in being affected of the first-born twin and the fact that concordance was only 35% for CD and 16% for UC monozygotic twins highlight the important role of environmental trigger factors.

Cited by 147 publications

References 51 publications

The microbiota in inflammatory bowel disease

The microbiota in inflammatory bowel disease

A functional methylome map of ulcerative colitis

Pathology of Inflammatory Bowel Disease

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