Exclusion of linkage between manic depressive illness and tyrosine hydroxylase and dopamine D2 receptor genes.

Mutations at the tyrosine hydroxylase or dopamine D2 receptor loci causing manic depressive illness are unlikely in two families reported here. Linkage was excluded for both loci assuming a dominant mode of transmission and for the tyrosine hydroxylase locus also assuming a recessive mode of transmission. The exclusion was significant using models based on severity of psychopathology and a model requiring severe illness also in first-degree relatives. Conservative genetic parameters were used to minimize misclassification.