POLYGENIC INHERITANCE OF TOURETTE SYNDROME, STUTTERING, ATTENTION-DEFICIT HYPERACTIVITY, CONDUCT, AND OPPOSITIONAL DEFIANT DISORDER - THE ADDITIVE AND SUBTRACTIVE EFFECT OF THE 3 DOPAMINERGIC GENES - DRD2, D-BETA-H, AND DAT1

Polymorphisms of three different dopaminergic genes, dopamine D-2 rece ptor (DRD2), dopamine beta-hydroxylase (D beta H), and dopamine transp orter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant c orrelation with various behavioral variables in these subjects. The ad ditive and subtractive effects of the three genes were examined by gen otyping all three genes in the same set of subjects. For 9 of 20 TS as sociated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant assoc iations were, in order, attention deficit hyperactivity disorder (ADHD ), stuttering, oppositional defiant, ties, conduct, obsessive-compulsi ve, mania, alcohol abuse, and general anxiety - behaviors that constit ute the most overt clinical aspects of TS. For 16 of the 20 behavior s cores there was a linear progressive decrease in the mean score with p rogressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering, oppositional defiant and conduct di sorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this techniqu e. (C) 1996 Wiley-Liss, Inc.