Am J Psychiatry 1993; 150:449-453
Copyright © 1993 by American Psychiatric Association
Exclusion of close linkage of Tourette's syndrome to D1 dopamine receptor
J Gelernter, JL Kennedy, DK Grandy, QY Zhou, O Civelli, DL Pauls, A Pakstis, R Kurlan, RK Sunahara and HB Niznik
Department of Psychiatry, Child Study Center, New Haven, Conn.
OBJECTIVE: The authors' goal was to establish if a mutation in D1 dopamine
receptor locus (DRD1), or one genetically close to it, could cause Gilles
de la Tourette's syndrome. METHOD: DRD1 and linked markers (D5S36, D5S61,
and D5S62) were studied in a large Mennonite Tourette's syndrome kindred.
Only individuals with the full Tourette's syndrome were considered to be
affected in one series of analyses; in another series the diagnostic
spectrum was broadened to include chronic multiple tics. Liability classes
were defined to take into account age at onset and sex differences;
dominant inheritance was assumed. The authors' version of the LINKMAP
program of the LINKAGE package modified to run under distributed parallel
processing (Linda LINKMAP) was used for the multipoint linkage analysis.
RESULTS: Complete (theta = 0.0) linkage of Tourette's syndrome with DRD1
was ruled out (lod score of - 10.1) when the disease was defined narrowly.
The area of exclusion of linkage (lod score between -2 and -10.5) extended
from map position - 0.10 to map position 0.50. The authors conducted an
additional (centromeric) multipoint analysis with D5S36 as well as
glucocorticoid receptor (GRL) and D5S22, resulting in an overlapping area
of exclusion to map position -0.30 when the disease was defined narrowly.
CONCLUSIONS: This result provides strong evidence against linkage of the
DRD1 D1 dopamine receptor locus with Tourette's syndrome. This exclusion
extends the authors' earlier work with the dopamine system in Tourette's
syndrome to exclude the two best characterized dopamine receptors from
linkage with Tourette's syndrome.
