CLADISTIC-ANALYSIS OF DISEASE ASSOCIATION WITH TYROSINE-HYDROXYLASE -APPLICATION TO MANIC-DEPRESSIVE DISEASE AND ALCOHOLISM

We evaluated the involvement of tyrosine hydroxylase (TH) mutations in susceptibility to manic-depressive disease (MDD) and alcoholism (ALC) with a cladistics-based association analysis. Eighty-one probands wit h MDD, 113 probands with alcoholism, and 80 normal controls were teste d for differences in frequency of nine haplotypes at the TH locus. The haplotypes were comprised of four restriction fragment length polymor phisms spanning the TH gene. A cladogram constructed from the haplotyp es provided the evolutionary context for a nested statistical analysis . Statistically significant evidence was found for association of a su bgroup of the sample for each of the disorders with different branches of the gene tree, but the findings were sensitive to minor changes in estimated haplotype frequencies. Am. J. Med. Genet. 74:289-295, 1997. (C) 1997 Wiley-Liss, Inc.