Linkage analysis of Tourette syndrome in a large Utah pedigree

Stacey Knight; Hilary Coon; Michael Johnson; Mark F. Leppert; Nicola J. Camp; William M. McMahon; D. Cath; P. Heutink; M. Grados; H. S. Singer; J. T. Walkup; C. Illmann; S. Santangelo; S. E. Stewart; J. Scharf; D. L. Pauls; N. J. Cox; S. Service; D. Keen-Kim; C. Sabatti; N. Freimer; M. M. Robertson; G. A. Rouleau; J. B. Riviere; S. Chouinard; F. Richer; P. Lesperance; Y. Dion; R. A. King; J. R. Kidd; A. J. Pakstis; J. F. Leckman; K. K. Kidd; G. Gericke; R. Kurlan; P. Como; D. Palumbo; A. Verkerk; B. A. Oostra; W. McMahon; M. Leppert; C. A. Mathews; P. Sandor; C. L. Barr

doi:10.1002/ajmg.b.31035

Linkage analysis of Tourette syndrome in a large Utah pedigree

Stacey Knight, Hilary Coon, Michael Johnson, Mark F. Leppert, Nicola J. Camp, William M. McMahon, D. Cath, P. Heutink, M. Grados, H. S. Singer, J. T. Walkup, C. Illmann, S. Santangelo, S. E. Stewart, J. Scharf, D. L. Pauls, N. J. Cox, S. Service, D. Keen-Kim, C. SabattiN. Freimer, M. M. Robertson, G. A. Rouleau, J. B. Riviere, S. Chouinard, F. Richer, P. Lesperance, Y. Dion, R. A. King, J. R. Kidd, A. J. Pakstis, J. F. Leckman, K. K. Kidd, G. Gericke, R. Kurlan, P. Como, D. Palumbo, A. Verkerk, B. A. Oostra, W. McMahon, M. Leppert, C. A. Mathews, P. Sandor, C. L. Barr

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

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, highrisk 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.

Original language	English (US)
Pages (from-to)	656-662
Number of pages	7
Journal	American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume	153
Issue number	2
DOIs	https://doi.org/10.1002/ajmg.b.31035
State	Published - Mar 1 2010

Keywords

Linkage analysis
Tourette syndrome
Yale Global Tic Severity Scale

ASJC Scopus subject areas

Genetics(clinical)
Psychiatry and Mental health
Cellular and Molecular Neuroscience

Access to Document

10.1002/ajmg.b.31035

Cite this

Knight, S., Coon, H., Johnson, M., Leppert, M. F., Camp, N. J., McMahon, W. M., Cath, D., Heutink, P., Grados, M., Singer, H. S., Walkup, J. T., Illmann, C., Santangelo, S., Stewart, S. E., Scharf, J., Pauls, D. L., Cox, N. J., Service, S., Keen-Kim, D., ... Barr, C. L. (2010). Linkage analysis of Tourette syndrome in a large Utah pedigree. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 153(2), 656-662. https://doi.org/10.1002/ajmg.b.31035

Knight, S, Coon, H, Johnson, M, Leppert, MF, Camp, NJ, McMahon, WM, Cath, D, Heutink, P, Grados, M , Singer, HS, Walkup, JT, Illmann, C, Santangelo, S, Stewart, SE, Scharf, J, Pauls, DL, Cox, NJ, Service, S, Keen-Kim, D, Sabatti, C, Freimer, N, Robertson, MM, Rouleau, GA, Riviere, JB, Chouinard, S, Richer, F, Lesperance, P, Dion, Y, King, RA, Kidd, JR, Pakstis, AJ, Leckman, JF, Kidd, KK, Gericke, G, Kurlan, R, Como, P, Palumbo, D, Verkerk, A, Oostra, BA, McMahon, W, Leppert, M, Mathews, CA, Sandor, P & Barr, CL 2010, 'Linkage analysis of Tourette syndrome in a large Utah pedigree', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 153, no. 2, pp. 656-662. https://doi.org/10.1002/ajmg.b.31035

@article{1fdde08f6a8647898242c9da79e7177a,

title = "Linkage analysis of Tourette syndrome in a large Utah pedigree",

abstract = "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, highrisk 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.",

keywords = "Linkage analysis, Tourette syndrome, Yale Global Tic Severity Scale",

author = "Stacey Knight and Hilary Coon and Michael Johnson and Leppert, {Mark F.} and Camp, {Nicola J.} and McMahon, {William M.} and D. Cath and P. Heutink and M. Grados and Singer, {H. S.} and Walkup, {J. T.} and C. Illmann and S. Santangelo and Stewart, {S. E.} and J. Scharf and Pauls, {D. L.} and Cox, {N. J.} and S. Service and D. Keen-Kim and C. Sabatti and N. Freimer and Robertson, {M. M.} and Rouleau, {G. A.} and Riviere, {J. B.} and S. Chouinard and F. Richer and P. Lesperance and Y. Dion and King, {R. A.} and Kidd, {J. R.} and Pakstis, {A. J.} and Leckman, {J. F.} and Kidd, {K. K.} and G. Gericke and R. Kurlan and P. Como and D. Palumbo and A. Verkerk and Oostra, {B. A.} and W. McMahon and M. Leppert and Mathews, {C. A.} and P. Sandor and Barr, {C. L.}",

year = "2010",

month = mar,

day = "1",

doi = "10.1002/ajmg.b.31035",

language = "English (US)",

volume = "153",

pages = "656--662",

journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",

issn = "1552-4841",

publisher = "Wiley-Liss Inc.",

number = "2",

}

TY - JOUR

T1 - Linkage analysis of Tourette syndrome in a large Utah pedigree

AU - Knight, Stacey

AU - Coon, Hilary

AU - Johnson, Michael

AU - Leppert, Mark F.

AU - Camp, Nicola J.

AU - McMahon, William M.

AU - Cath, D.

AU - Heutink, P.

AU - Grados, M.

AU - Singer, H. S.

AU - Walkup, J. T.

AU - Illmann, C.

AU - Santangelo, S.

AU - Stewart, S. E.

AU - Scharf, J.

AU - Pauls, D. L.

AU - Cox, N. J.

AU - Service, S.

AU - Keen-Kim, D.

AU - Sabatti, C.

AU - Freimer, N.

AU - Robertson, M. M.

AU - Rouleau, G. A.

AU - Riviere, J. B.

AU - Chouinard, S.

AU - Richer, F.

AU - Lesperance, P.

AU - Dion, Y.

AU - King, R. A.

AU - Kidd, J. R.

AU - Pakstis, A. J.

AU - Leckman, J. F.

AU - Kidd, K. K.

AU - Gericke, G.

AU - Kurlan, R.

AU - Como, P.

AU - Palumbo, D.

AU - Verkerk, A.

AU - Oostra, B. A.

AU - McMahon, W.

AU - Leppert, M.

AU - Mathews, C. A.

AU - Sandor, P.

AU - Barr, C. L.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - 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, highrisk 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.

AB - 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, highrisk 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.

KW - Linkage analysis

KW - Tourette syndrome

KW - Yale Global Tic Severity Scale

UR - http://www.scopus.com/inward/record.url?scp=77349106005&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77349106005&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.31035

DO - 10.1002/ajmg.b.31035

M3 - Article

C2 - 19777563

AN - SCOPUS:77349106005

SN - 1552-4841

VL - 153

SP - 656

EP - 662

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 2

ER -

Linkage analysis of Tourette syndrome in a large Utah pedigree

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this