Genetic epidemiology of inflammatory bowel disease, early twin and family studies

Abstract

The influence of genetics in the etiology of inflammatory bowel disease (IBD) was initially demonstrated by epidemiological data, including differences in prevalence among different ethnic groups, familial aggregation of IBD, concordance in twins, and association with genetic syndromes. These early observations commenced the successful era of molecular genetics in IBD that has illuminated the complexity of the genetic and environmental interaction in IBD. Advances in molecular genetics have dramatically improved the resolution of the IBD genome. Yet, some of the key epidemiological observations are still unanswered from a molecular perspective. The observed high heritability in Crohn's disease can be explained only in part by the identified genetic risk loci. Possible contributions of other molecular mechanisms of heritability, such as epigenetics, are largely yet to be explored. Similarly, pronounced phenotypic similarities have been observed within multiplex families and especially within concordant monozygotic twin pairs with Crohn's disease, suggesting that genetics also influences the phenotype of the disease. However, only a few loci have been independently associated with subphenotypes of Crohn's disease and ulcerative colitis, and the underlying molecular mechanism behind the observed epidemiologic association is poorly understood. The possible impact of environmental factors also needs to be taken into account, since exposure to individual risk factors may be associated with certain subphenotypes of Crohn's disease and ulcerative colitis. Ongoing longitudinal studies with periodic measurements in subjects at high risk, that is, siblings and offspring below or around the peak age of onset of IBD, will probably become an important tool to elucidate the genetic and environmental interactions underlying this archetypal complex disease entity.