FURTHER TESTS FOR LINKAGE OF BIPOLAR AFFECTIVE-DISORDER TO THE TYROSINE-HYDROXYLASE GENE LOCUS ON CHROMOSOME 11P15 IN A NEW SERIES OF MULTIPLEX BRITISH AFFECTIVE-DISORDER PEDIGREES

Objective: This study was undertaken to confirm or refute previous rep orts that link bipolar affective disorder to polymorphic DNA markers a t or near the gene for tyrosine hydroxylase. Method: A previous linkag e analysis, which wed a tetranucleotide repeat polymorphism at the tyr osine hydroxylase locus, of six Icelandic families was extended to inc lude a new series of 17 multiply affected British families. Results: O verall lod scores under the assumption of locus heterogeneity were bet ween 1.20 and 1.40 at zero recombination with tyrosine hydroxylase, an d these scores persisted across three affective disorder models. Concl usions: These results provide some support for linking affective disor der to this genetic region and suggest that additional linkage and ass ociation studies should be conducted to determine whether tyrosine hyd roxylase or a nearby locus contributes to susceptibility to bipolar af fective disorder in some families.