Recent insights into the genetics of inflammatory bowel disease

Judy H. Cho, Steven Brant

Research output: Contribution to journalArticle

265 Citations (Scopus)

Abstract

Inflammatory bowel diseases (IBDs) are complex, multifactorial disorders that comprise Crohn's disease (CD) and ulcerative colitis (UC). Genome-wide association studies have identified approximately 100 loci that are significantly associated with IBD. These loci implicate a diverse array of genes and pathophysiologic mechanisms, including microbe recognition, lymphocyte activation, cytokine signaling, and intestinal epithelial defense. Consistent with epidemiologic predictions, many IBD-associated loci demonstrate genome-wide significant associations to both CD and UC, notably, genes whose products function in the interleukin-23 pathway, and transcription factors, including NK2 transcription factor related, locus 3 (NKX2-3), SMAD3, STAT3, ZMIZ1, and c-REL. Although CD and UC are both associated with genomic regions that implicate products of genes involved in leukocyte trafficking, there is evidence for association patterns that are distinct between CD and UC. CD-predominant associations include NOD2 and genes that regulate autophagy. In UC, the predominant association signal is on chromosome 6p21, in the major histocompatibility complex region, near HLA class II genes. UC-predominant loci have also implicated genes mediating epithelial defense function. There is a striking overlap of loci between diseases, which could provide comparative insight into mechanisms of disease pathogenesis. Genes that encode factors that function in the interleukin-23 pathway have been associated with a number of chronic inflammatory diseases, notably psoriasis and ankylosing spondylitis. Distinct genetic associations indicate that the colitis associated with primary sclerosing cholangitis is pathophysiologically distinct from UC that is not associated with primary sclerosing cholangitis. As many as 14 susceptibility loci are shared between IBD and celiac disease, indicating significant overlap in pathophysiology. Future genetic studies will be directed toward identifying uncommon variations with potentially greater statistical effects, defining population differences, and more completely accounting for familial transmission of disease.

Original languageEnglish (US)
Pages (from-to)1704-1712.e2
JournalGastroenterology
Volume140
Issue number6
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Fingerprint

Ulcerative Colitis
Inflammatory Bowel Diseases
Crohn Disease
Genes
Interleukin-23
Sclerosing Cholangitis
Transcription Factors
MHC Class II Genes
Genome-Wide Association Study
Ankylosing Spondylitis
Autophagy
Celiac Disease
Colitis
Lymphocyte Activation
Major Histocompatibility Complex
Psoriasis
Leukocytes
Chronic Disease
Chromosomes
Genome

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Cho, Judy H. ; Brant, Steven. / Recent insights into the genetics of inflammatory bowel disease. In: Gastroenterology. 2011 ; Vol. 140, No. 6. pp. 1704-1712.e2.
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Recent insights into the genetics of inflammatory bowel disease. / Cho, Judy H.; Brant, Steven.

In: Gastroenterology, Vol. 140, No. 6, 01.01.2011, p. 1704-1712.e2.

Research output: Contribution to journalArticle

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