Fifty years of genetic epidemiology, with special reference to Japan.

Genetic epidemiology deals with etiology, distribution, and control of disease in groups of relatives and with inherited causes of disease in populations. It took its first steps before its recognition as a discipline, and did not reach its present scope until the Human Genome Project succeeded. The intimate relationship between genetics and epidemiology was discussed by Neel and Schull (1954), just a year after Watson and Crick reported the DNA double helix, and 2 years before human cytogenetics and the Japan Society of Human Genetics were founded. It is convenient to divide the next half-century into three phases. The first of these (1956-1979) was before DNA polymorphisms were typed, and so the focus was on segregation and linkage of major genes, cytogenetics, population studies, and biochemical genetics. The next phase (1980-2001) progressively identified DNA polymorphisms and their application to complex inheritance. The last phase began with a reliable sequence of the human genome (2002), followed by exploration of genomic diversity. Linkage continues to be useful to study recombination and to map major genes, but association mapping gives much greater resolution and enables studies of complex inheritance. The generation now entering human genetics will have collaborative opportunities undreamed of a few years ago, without the independence that led to great advances during the past half-century.