Linkage studies of psychiatric disorders.

Linkage analysis has been successful in identifying the genetic basis of numerous Mendelian diseases. These successes were due in part to the rapid developments in molecular biology, which have yielded a plethora of informative genetic markers. Although there is strong evidence that the manifestation of schizophrenia and bipolar affective disorders is controlled by genes, no evidence for linkage has been established. For psychiatric disorders, the most important limiting factor is likely to be the lack of single loci with very large effects that occur with any relevant frequency. The difficulties of linkage studies in psychiatric disorders are discussed with reference to non-psychiatric genetic diseases for which linkage to genetic markers has been successful. Recommendations for collecting information to clarify the patterns of transmission of the psychiatric disorders are described.