Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome.

A genome scan of the hoarding phenotype (a component of obsessive-compulsive disorder) was conducted on 77 sib pairs collected by the Tourette Syndrome Association International Consortium for Genetics (TSAICG). All sib pairs were concordant for a diagnosis of Gilles de la Tourette syndrome (GTS). However, the analyses reported here were conducted for hoarding as both a dichotomous trait and a quantitative trait. Not all sib pairs in the sample were concordant for hoarding. Standard linkage analyses were performed using GENEHUNTER and Haseman-Elston methods. In addition, novel analyses with a recursive-partitioning technique were employed. Significant allele sharing was observed for both the dichotomous and the quantitative hoarding phenotypes for markers at 4q34-35 (P=.0007), by use of GENEHUNTER, and at 5q35.2-35.3 (P=.000002) and 17q25 (P=.00002), by use of the revisited Haseman-Elston method. The 4q site is in proximity to D4S1625, which was identified by the TSAICG as a region linked to the GTS phenotype. The recursive-partitioning technique examined multiple markers simultaneously. Results suggest joint effects of specific loci on 5q and 4q, with an overall P value of.000003. Although P values were not adjusted for multiple comparison, nearly all were much smaller than the customary significance level of.0001 for genomewide scans.

[1]  M. Xiong,et al.  Recursive partitioning for tumor classification with gene expression microarray data , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  M A Province,et al.  Tree‐based recursive partitioning methods for subdividing sibpairs into relatively more homogeneous subgroups , 2001, Genetic epidemiology.

[3]  B. Leventhal,et al.  Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder , 2001, Molecular Psychiatry.

[4]  J. Weber,et al.  Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23-24 in South African Afrikaners. , 2001, American journal of medical genetics.

[5]  H. Zhang,et al.  Symptom dimensions in obsessive-compulsive disorder: toward quantitative phenotypes. , 2001, American journal of medical genetics.

[6]  T. Beaty,et al.  Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex. , 2000, American journal of human genetics.

[7]  Heping Zhang,et al.  Use of classification trees for association studies , 2000, Genetic epidemiology.

[8]  R. Frost,et al.  Mood, personality disorder symptoms and disability in obsessive compulsive hoarders: a comparison with clinical and nonclinical controls. , 2000, Behaviour research and therapy.

[9]  M M Weissman,et al.  The epidemiology and cross-national presentation of obsessive-compulsive disorder. , 2000, The Psychiatric clinics of North America.

[10]  R C Elston,et al.  Haseman and Elston revisited , 2000, Genetic epidemiology.

[11]  W. Goodman,et al.  Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. , 1999, American journal of medical genetics.

[12]  S. Rauch,et al.  Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder. , 1999, The American journal of psychiatry.

[13]  M. Antony,et al.  Symptom structure in obsessive-compulsive disorder: a confirmatory factor-analytic study. , 1999, Behaviour research and therapy.

[14]  E. Smeraldi,et al.  Complex segregation analysis for obsessive compulsive disorder and related disorders. , 1999, American journal of medical genetics.

[15]  D. Cohen,et al.  Tourette's Syndrome -- Tics, Obsessions, Compulsions: Developmental Psychopathology and Clinical Care , 1998 .

[16]  D. Black,et al.  Hoarding and treatment response in 38 nondepressed subjects with obsessive-compulsive disorder. , 1998, The Journal of clinical psychiatry.

[17]  C. McDougle,et al.  Symptoms of obsessive-compulsive disorder. , 1997, The American journal of psychiatry.

[18]  N. Risch,et al.  Mapping quantitative-trait loci in humans by use of extreme concordant sib pairs: selected sampling by parental phenotypes. , 1996, American journal of human genetics.

[19]  R. Frost,et al.  The value of possessions in compulsive hoarding: patterns of use and attachment. , 1995, Behaviour research and therapy.

[20]  E. Lander,et al.  Complete multipoint sib-pair analysis of qualitative and quantitative traits. , 1995, American journal of human genetics.

[21]  N Risch,et al.  Extreme discordant sib pairs for mapping quantitative trait loci in humans. , 1995, Science.

[22]  D. E. Walker,et al.  "Just right" perceptions associated with compulsive behavior in Tourette's syndrome. , 1994, The American journal of psychiatry.

[23]  L. Baer Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders. , 1994, The Journal of clinical psychiatry.

[24]  D. Cohen,et al.  An epidemiologic study of Gilles de la Tourette's syndrome in Israel. , 1993, Archives of general psychiatry.

[25]  N. Risch Linkage strategies for genetically complex traits. II. The power of affected relative pairs. , 1990, American journal of human genetics.

[26]  W. Goodman,et al.  The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. , 1989, Archives of general psychiatry.

[27]  D. Cohen,et al.  The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. , 1989, Journal of the American Academy of Child and Adolescent Psychiatry.

[28]  S. Sorenson,et al.  The epidemiology of obsessive-compulsive disorder in five US communities. , 1988, Archives of general psychiatry.

[29]  S. Khanna,et al.  Obsessive Compulsive Disorder, Anxiety and Depression , 1987 .

[30]  N E Morton,et al.  A unified model for complex segregation analysis. , 1983, American journal of human genetics.

[31]  M. Weissman,et al.  Best estimate of lifetime psychiatric diagnosis: a methodological study. , 1982, Archives of general psychiatry.

[32]  J. Feighner,et al.  A family study of Gilles de la Tourette syndrome. , 1976, Diseases of the nervous system.

[33]  R. Elston,et al.  The investigation of linkage between a quantitative trait and a marker locus , 1972, Behavior genetics.

[34]  Heping Zhang,et al.  Tree‐Based Linkage and Association Analyses of Asthma , 2001, Genetic epidemiology.

[35]  Wayne K. Goodman,et al.  Obsessive-compulsive disorder : contemporary issues in treatment , 2000 .

[36]  Burton H. Singer,et al.  Recursive partitioning in the health sciences , 1999 .

[37]  D. Pauls A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. The Tourette Syndrome Association International Consortium for Genetics. , 1999, American journal of human genetics.

[38]  D C Rao,et al.  CAT scans, PET scans, and genomic scans , 1998, Genetic epidemiology.

[39]  Robert W. Lucky,et al.  Just right , 1997 .

[40]  C. McDougle,et al.  Tic-related vs. non-tic-related obsessive compulsive disorder. , 1994, Anxiety.

[41]  Dc Washington Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. , 1994 .

[42]  D. E. Walker,et al.  Premonitory urges in Tourette's syndrome. , 1993, The American journal of psychiatry.

[43]  H. Nicolini,et al.  Family study of obsessive-compulsive disorder in a Mexican population. , 1993, Archives of medical research.

[44]  R. Hoehn-Saric,et al.  A family study of obsessive-compulsive disorder. , 1992, Archives of general psychiatry.