Genetic heterogeneity in common disease.

It is not apparent that diabetes mellitus and peptic ulcer disease are not single polygenic diseases, but are each genetically heterogeneous, consisting of numerous distinct entities. The delineation of genetic heterogeneity has important implications for genetic counseling, treatment, and prognosis, and is essential in determining the pathophysiology and etiology of a disorder. Unless each of the distinct component diseases of a symptom complex has been identified and separated, the basic pathophysiological abnormalities cannot be identified, and a common biochemical abnormality will not be found in all affected individuals. In approaching the genetics of any common disease disorder in man, heterogeneity must first be unmasked, and genetic and pathogenetic studies must be separately performed in each of the component, etiologically distinct disorders producing the aberrant phenotype.