LINKAGE DISEQUILIBRIUM BETWEEN THE DOPAMINE TRANSPORTER GENE (DAT1) AND BIPOLAR DISORDER - EXTENDING THE TRANSMISSION DISEQUILIBRIUM TEST(TDT) TO EXAMINE GENETIC-HETEROGENEITY

Since its introduction into the statistical genetics literature, the t ransmission disequilibrium test (TDT) has seen widespread use in analy ses of linkage and association due not only to its simplicity but also to its desirable properties relative to other within-family analytic methods. In this paper, we describe an extension to the TDT useful for examining genetic heterogeneity. This extension uses contingency tabl e analyses such as log-linear analysis to test for differences in link age disequilibrium across levels of one or more moderator variables. W e applied these analyses to test for linkage disequilibrium between th e dopamine transporter gene (DAT1) and bipolar disorder, as well as fo r genetic heterogeneity due to sex, diagnostic breadth, and study site . Using data from two studies (the UCSD/UBC and Cardiff data sets), we found evidence suggesting linkage disequilibrium between DAT1 and bip olar disorder, as well as heterogeneity due to diagnostic breadth and study site. (C) 1997 Wiley-Liss, Inc.