The genetics of complex diseases (Reprinted from Trends in Biochemical Science, vol 12, Dec., 1999)

Genetic factors influence virtually every human disorder, determining disea se susceptibility or resistance and interactions with environmental factors . Our recent successes in the genetic mapping and identification of the mol ecular basis of mendelian traits have been remarkable. Now, attention is ra pidly shifting to more-complex, and more-prevalent, genetic disorders and t raits that involve multiple genes and environmental effects, such as cardio vascular disease, diabetes, rheumatoid arthritis and schizophrenia. Rather than being due to specific and relatively rare mutations, complex diseases and traits result principally from genetic variation that is relatively com mon in the general population. Unfortunately, despite extensive efforts by many groups, only a few genetic regions and genes involved in complex disea ses have been identified. Completion of the human genome sequence will be a seminal accomplishment, but it will not provide an immediate solution to t he genetics of complex traits.