Unsolved problems in genetic epidemiology.

Genetic epidemiology faces six critical issues: its scope, genetic mapping, complex inheritance, population structure, nonmendelian genetics, and the internationalization of genetics. To solve these problems the scope must be broadened to include normal variation, although much of descriptive genetics will be lost to related sciences. Genetic mapping continues to play an essential role for positional cloning and chromosome architecture, which sequencing cannot replace. A large part of current effort is devoted to complex inheritance, requiring development of methods to pool multiple studies. The effect of population structure on forensic DNA identification appears to have been solved, but its effect for complex inheritance and genetic loads remains to be clarified. Populational analysis of non-Mendelian genetics has been largely neglected. The infrastructure of genetics must be internationalized if legal and ethical principles are to be supported and genetic epidemiology is to realise its potential.