Role of genetics in pediatric inflammatory bowel disease

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and unclassified IBD, is characterized by chronic intestinal inflammation and has a multifactorial etiology with complex interactions between genetic and environmental factors. The genetics of IBD are believed to be common and complex with over 163 associated genetic loci. However, the genetic contribution of the majority of these common loci is small, and the effect sizes are low. Although childhood onset IBD represents only 10% to 25% of all IBD cases, in depth research into the genetic networks of pediatric IBD has revealed exciting new developments and unsuspected pathways. Recent pediatric studies have revealed an increasing spectrum of human monogenic diseases with high effect sizes or penetrance that can present with IBD or IBD-like intestinal inflammation. A substantial proportion of patients with these genetic defects present with very early onset of intestinal inflammation, with onset of IBD at less than 10 years of age. There is also considerable overlap with primary immunodeficiencies and very early onset IBD. This review summarizes the current understanding of the genetics of pediatric IBD with a focus on the very early onset population and discusses the promising results from the effort of finding missing heritability of IBD from studying pediatric population.