A logistic regression extension of the transmission disequilibrium test for continuous traits: Application to linkage disequilibrium between alcoholism and the candidate genes DRD2 and ADH3

The transmission disequilibrium test (TDT) recently has become a popular me thod of testing for linkage in the presence of association due to its simpl icity and advantages over other within-family analytic methods. In this pap er, we describe a logistic regression extension to the TDT that can be used to test for differences in linkage disequilibrium as a function of one or more continuous and/or categorical explanatory variables. We highlight impo rtant features of this method and demonstrate some of its possible uses. We applied these analyses to test for linkage disequilibrium between the dopa mine receptor D2 (DRD2) and alcohol dehydrogenase 3 (ADH3) genes and both d iagnostic and quantitative indices of alcoholism Using data from the Collab orative Study on the Genetics of Alcoholism data set, we found evidence sug gesting linkage disequilibrium between DRD2 and ADH3 and quantitative indic es of alcoholism and correlated phenotypes corresponding to smoking and per sonality None of the evidence for linkage disequilibrium varied by sex or a ge. (C) 1999 Wiley-Liss, Inc.