Linkage analysis of Tourette syndrome in a large Utah pedigree.
Tourette syndrome (TS) is a neuropsychiatric disorder characterized by multiple motor and phonic tics. The heritability of TS has been well established, yet there is a lack of consensus in genome-wide linkage studies. The purpose of this study was to conduct a genome-wide linkage analysis on a unique, large, high-risk TS Utah pedigree. We examined a qualitative trait (TS1) where cases had a definitive diagnosis of TS as observed by a clinical interviewer (n = 66) and a quantitative phenotype based on the total Yale global motor and phonic tic severity scores (n = 102). Both parametric and non-parametric multipoint linkage analyses based on MCMC methods were performed using a 10 cM spaced micro-satellite autosomal marker set. Two regions of interest were identified under affecteds-only recessive models; a LOD score of 3.3 on chromosome 1p for Yale tic severity and a LOD score of 3.1 on chromosome 3p for the TS1 phenotype. Twenty-seven individuals shared linked segregating haplotypes for the 1p region. They had significantly higher Yale tic phonic scores than non-sharers (P = 0.01). There were 46 haplotype sharers on chromosome 3p with significantly higher percentage of females among these individuals compared to the non-sharers (P = 0.03). The significant linkage peaks on chromosomes 1p and 3p are in new areas of the genome for TS, and replication of these findings is necessary.
Knight
Stacey
S
Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah.
Coon
Hilary
H
Department of Psychiatry, University of Utah, Salt Lake City, Utah.
Johnson
Michael
M
Department of Psychiatry, University of Utah, Salt Lake City, Utah.
Leppert
Mark F
MF
Department of Human Genetics, University of Utah, Salt Lake City, Utah.
Camp
Nicola J
NJ
Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah.
McMahon
William M
WM
Department of Psychiatry, University of Utah, Salt Lake City, Utah.
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D005879:Tourette Syndrome / Q000235:genetics*; D014589:Utah