Journal of Psychosomatic Research
Volume 67, Issue 6 , Pages 533-545 , December 2009

The genetics of Tourette syndrome: A review

  • Julia A. O'Rourke

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    • Biomedical Engineering Department, Tufts University, Medford, MA, USA
    • ,
  • Jeremiah M. Scharf

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    • ,
  • Dongmei Yu

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    • ,
  • David L. Pauls

      Affiliations

    • Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
    • Corresponding Author InformationCorresponding author. Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. Fax: +1 617 726 0830.

Received 19 February 2009 ,Revised 23 June 2009 ,Accepted 26 June 2009.

References 

  1. de la Tourette G. Etude sur une affection nerveuse caracterisee par de l'indoordination motrice accompagnee d'echolalie et al copralalie. Archives or Neurology. 1885;9:19–42
  2. Pauls DL, Hurst CR, Kruger SD, Leckman JF, Kidd KK, Cohen DJ. Gilles de la Tourette's syndrome and attention deficit disorder with hyperactivity. Evidence against a genetic relationship. Arch Gen Psychiatry. 1986;43:1177–1179
  3. Kidd KK, Prusoff BA, Cohen DJ. Familial pattern of Gilles de la Tourette syndrome. Arch Gen Psychiatry. 1980;37:1336–1339
  4. Pauls DL, Cohen DJ, Heimbuch R, Detlor J, Kidd KK. Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics. Arch Gen Psychiatry. 1981;38:1091–1093
  5. Pauls DL, Kruger SD, Leckman JF, Cohen DJ, Kidd KK. The risk of Tourette's syndrome and chronic multiple tics among relatives of Tourette's syndrome patients obtained by direct interview. J Am Acad Child Psychiatry. 1984;23:134–137
  6. Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome. Am J Hum Genet. 1991;48:154–163
  7. Eapen V, Pauls DL, Robertson MM. Evidence for autosomal dominant transmission in Tourette's syndrome. United Kingdom cohort study. Br J Psychiatry. 1993;162:593–596
  8. Walkup JT, LaBuda MC, Singer HS, Brown J, Riddle MA, Hurko O. Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance. Am J Hum Genet. 1996;59:684–693
  9. Hebebrand J, Klug B, Fimmers R, Seuchter SA, Wettke-Schafer R, Deget F, et al. Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome. J Psychiatr Res. 1997;31:519–530
  10. Kano Y, Ohta M, Nagai Y, Pauls DL, Leckman JF. A family study of Tourette syndrome in Japan. Am J Med Genet. 2001;105:414–421
  11. Saccomani L, Fabiana V, Manuela B, Giambattista R. Tourette syndrome and chronic tics in a sample of children and adolescents. Brain Dev. 2005;27:349–352
  12. Stewart SE, Illmann C, Geller DA, Leckman JF, King R, Pauls DL. A controlled family study of attention-deficit/hyperactivity disorder and Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 2006;45:1354–1362
  13. Smoller JW, Sheidley BR, Tsuang MT. Psychiatric genetics applications in clinical practice. Washington (DC): American Psychiatric Publishing, Inc.; 2008;
  14. Freeman RD, Fast DK, Burd L, Kerbeshian J, Robertson MM, Sandor P. An international perspective on Tourette syndrome: selected findings from 3,500 individuals in 22 countries. Dev Med Child Neurol. 2000;42:436–447
  15. Mol Debes NM, Hjalgrim H, Skov L. Validation of the presence of comorbidities in a Danish clinical cohort of children with Tourette syndrome. J Child Neurol. 2008;23:1017–1027
  16. Freeman RD. Tic disorders and ADHD: answers from a world-wide clinical dataset on Tourette syndrome. Eur Child Adolesc Psychiatry. 2007;16(Suppl 1):15–23
  17. Khalifa N, von Knorring AL. Psychopathology in a Swedish population of school children with tic disorders. J Am Acad Child Adolesc Psychiatry. 2006;45:1346–1353
  18. Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry. 1988;45:1094–1099
  19. Weissman MM, Bland RC, Canino GJ, Greenwald S, Hwu HG, Lee CK, et al The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry. 1994;55(Suppl):5–10
  20. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–948
  21. Pringsheim T, Lang A, Kurlan R, Pearce M, Sandor P. Understanding disability in Tourette syndrome. Dev Med Child Neurol. 2008;468–472
  22. Budman CL, Bruun RD, Park KS, Lesser M, Olson M. Explosive outbursts in children with Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 2000;39:1270–1276
  23. Budman CL, Bruun RD, Park KS, Olson ME. Rage attacks in children and adolescents with Tourette's disorder: a pilot study. J Clin Psychiatry. 1998;59:576–580
  24. Pauls DL. The genetics of obsessive compulsive disorder: a review of the evidence. Am J Med Genet C Semin Med Genet. 2008;148:133–139
  25. Pauls DL, Towbin KE, Leckman JF, Zahner GE, Cohen DJ. Gilles de la Tourette's syndrome and obsessive-compulsive disorder. Evidence supporting a genetic relationship. Arch Gen Psychiatry. 1986;43:1180–1182
  26. Curtis D, Robertson MM, Gurling HM. Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome. Br J Psychiatry. 1992;160:845–849
  27. McMahon WM, van de Wetering BJ, Filloux F, Betit K, Coon H, Leppert M. Bilineal transmission and phenotypic variation of Tourette's disorder in a large pedigree. J Am Acad Child Adolesc Psychiatry. 1996;35:672–680
  28. Pauls DL, Alsobrook JP, Goodman W, Rasmussen S, Leckman JF. A family study of obsessive-compulsive disorder. Am J Psychiatry. 1995;152:76–84
  29. Grados MA, Riddle MA, Samuels JF, Liang KY, Hoehn-Saric R, Bienvenu OJ, et al. The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study. Biol Psychiatry. 2001;50:559–565
  30. Leonard HL, Lenane MC, Swedo SE, Rettew DC, Gershon ES, Rapoport JL. Tics and Tourette's disorder: a 2- to 7-year follow-up of 54 obsessive-compulsive children. Am J Psychiatry. 1992;149:1244–1251
  31. Nestadt G, Samuels J, Riddle M, Bienvenu OJ, Liang KY, LaBuda M, et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry. 2000;57:358–363
  32. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237–248
  33. Comings DE, Comings BGA. controlled study of Tourette syndrome. I. Attention-deficit disorder, learning disorders, and school problems. Am J Hum Genet. 1987;41:701–741
  34. Knell ER, Comings DE. Tourette's syndrome and attention-deficit hyperactivity disorder: evidence for a genetic relationship. J Clin Psychiatry. 1993;54:331–337
  35. Pauls DL, Leckman JF, Cohen DJ. Familial relationship between Gilles de la Tourette's syndrome, attention deficit disorder, learning disabilities, speech disorders, and stuttering. J Am Acad Child Adolesc Psychiatry. 1993;32:1044–1050
  36. ORourke JA, Scharf JM, Stewart E, Platko J, Illmann C, Geller D, King RA, Leckman JF, Pauls D. The familial association of Tourette's disorder and ADHD: the impact of OCD symptoms. Submitted for publication.
  37. Spencer T, Biederman J, Harding M, O'Donnell D, Wilens T, Faraone S, et al. Disentangling the overlap between Tourette's disorder and ADHD. J Child Psychol Psychiatry. 1998;39:1037–1044
  38. McMahon WM, Carter AS, Fredine N, Pauls DL. Children at familial risk for Tourette's disorder: child and parent diagnoses. Am J Med Genet B Neuropsychiatr Genet. 2003;121B:105–111
  39. Grados MA, Mathews CA. Latent class analysis of Gilles de la Tourette syndrome using comorbidities: clinical and genetic implications. Biol Psychiatry. 2008;64:219–225
  40. Robertson MM, Althoff RR, Hafez A, Pauls DL. Principal components analysis of a large cohort with Tourette syndrome. Br J Psychiatry. 2008;193:31–36
  41. Comings DE, Comings BG, Devor EJ, Cloninger CR. Detection of major gene for Gilles de la Tourette syndrome. Am J Hum Genet. 1984;36:586–600
  42. Baron M, Shapiro E, Shapiro A, Rainer JD. Genetic analysis of Tourette syndrome suggesting major gene effect. Am J Hum Genet. 1981;33:767–775
  43. Devor EJ. Complex segregation analysis of Gilles de la Tourette syndrome: further evidence for a major locus mode of transmission. Am J Hum Genet. 1984;36:704–709
  44. Hasstedt SJ, Leppert M, Filloux F, van de Wetering BJ, McMahon WM. Intermediate inheritance of Tourette syndrome, assuming assortative mating. Am J Hum Genet. 1995;57:682–689
  45. Kidd KK, Pauls DL. Genetic hypotheses for Tourette syndrome. Adv Neurol. 1982;35:243–249
  46. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors. Evidence for autosomal dominant transmission. N Engl J Med. 1986;315:993–997
  47. Pauls DL, Pakstis AJ, Kurlan R, Kidd KK, Leckman JF, Cohen DJ, et al. Segregation and linkage analyses of Tourette's syndrome and related disorders. J Am Acad Child Adolesc Psychiatry. 1990;29:195–203
  48. Price RA, Pauls DL, Kruger SD, Caine ED. Family data support a dominant major gene for Tourette syndrome. Psychiatry Res. 1988;24:251–261
  49. Seuchter SA, Hebebrand J, Klug B, Knapp M, Lehmkuhl G, Poustka F, et al. Complex segregation analysis of families ascertained through Gilles de la Tourette syndrome. Genet Epidemiol. 2000;18:33–47
  50. Comings DE, Comings BG, Knell E. Hypothesis: homozygosity in Tourette syndrome. Am J Med Genet. 1989;34:413–421
  51. Hanna PA, Janjua FN, Contant CF, Jankovic J. Bilineal transmission in Tourette syndrome. Neurology. 1999;53:813–818
  52. Kurlan R, Eapen V, Stern J, McDermott MP, Robertson MM. Bilineal transmission in Tourette's syndrome families. Neurology. 1994;44:2336–2342
  53. Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome. Arch Gen Psychiatry. 1985;42:815–820
  54. Hyde TM, Aaronson BA, Randolph C, Rickler KC, Weinberger DR. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology. 1992;42(3 Pt 1):652–658
  55. Barr CL, Wigg KG, Pakstis AJ, Kurlan R, Pauls D, Kidd KK, et al. Genome scan for linkage to Gilles de la Tourette syndrome. Am J Med Genet. 1999;88:437–445
  56. Curtis D, Brett P, Dearlove AM, McQuillin A, Kalsi G, Robertson MM, et al. Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13. Psychiatr Genet. 2004;14:83–87
  57. Leppert M, Peiffer A, Snyder B. Two loci of interest in a family with Tourette syndrome. Am J Hum Genet Suppl. 1996;59:A225
  58. Tourette Syndrome Association International Consortium for Genetics . A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. The Tourette Syndrome Association International Consortium for Genetics. Am J Hum Genet. 1999;65:1428–1436
  59. Tourette Syndrome Association International Consortium for Genetics . Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am J Hum Genet. 2007;80:265–272
  60. Scharf JM, Pauls DL. Genetics of tic disorders. In:  Rimoin D,  Connor JM,  Pyeritz RE,  Korf BR editor. Emery and Rimoin's principles and practices of medical genetics. Philadelphia: Churchill Livingstone/Elsevier; 2007;p. 2737–2754
  61. Cook EH, Scherer SW. Copy-number variations associated with neuropsychiatric conditions. Nature. 2008;455:919–923
  62. Weiss LA, Shen Y, Korn JM, Arking DE, Miller DT, Fossdal R, et al. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008;358:667–675
  63. Walsh T, McClellan JM, McCarthy SE, Addington AM, Pierce SB, Cooper GM, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320:539–543
  64. Stefansson H, Rujescu D, Cichon S, Pietilainen OP, Ingason A, Steinberg S, et al. Large recurrent microdeletions associated with schizophrenia. Nature. 2008;455:232–236
  65. International Schizophrenia Consortium . Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature. 2008;455:237–241
  66. Robertson MM, Trimble MR. Normal chromosomal findings in Gilles de la Tourette syndrome. Psychiatric Genetics. 1993;3:95–99
  67. Shen Y, Dies KA, Holm IA, Bridgemohan C, Sobeih MM, Caronna EB, Miller KJ, Frazier JA, Silverstein I, Picker J, Weissman L, Raffalli P, Jeste S, Demmer LA, Peters HK, Brewster SJ, Kowalczyk SJ, Rosen-Sheidley B, McGowan C, W. DA, Lincoln SA, Lowe KR, Schonwald A, Robbins M, Wolff R, Becker R, Nasir R, Milunsky JM, Rappaport L, Gusella JF, Walsh CA, Wu BL, Miller DT. Clinical genetic testing for patients with autism spectrum disorders. Pediatrics. Submitted for publication.
  68. Feuk L, Carson AR, Scherer SW. Structural variation in the human genome. Nat Rev Genet. 2006;7:85–97
  69. Shelley BP, Robertson MM, Turk J. An individual with Gilles de la Tourette syndrome and Smith-Magenis microdeletion syndrome: is chromosome 17p11.2 a candidate region for Tourette syndrome putative susceptibility genes?. J Intellect Disabil Res. 2007;51(Pt 8):620–624
  70. Dehning S, Riedel M, Muller N. Father-to-son transmission of 6;17 translocation in Tourette's syndrome. Am J Psychiatry. 2008;165:1051–1052
  71. Boghosian-Sell L, Comings DE, Overhauser J. Tourette syndrome in a pedigree with a 7;18 translocation: identification of a YAC spanning the translocation breakpoint at 18q22.3. Am J Hum Genet. 1996;59:999–1005
  72. Kroisel PM, Petek E, Emberger W, Windpassinger C, Wladika W, Wagner K. Candidate region for Gilles de la Tourette syndrome at 7q31. Am J Med Genet. 2001;101:259–261
  73. Petek E, Windpassinger C, Vincent JB, Cheung J, Boright AP, Scherer SW, et al. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am J Hum Genet. 2001;68:848–858
  74. Petek E, Schwarzbraun T, Noor A, Patel M, Nakabayashi K, Choufani S, et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol Genet Genomics. 2007;277:71–81
  75. Crawford FC, Ait-Ghezala G, Morris M, Sutcliffe MJ, Hauser RA, Silver AA, et al. Translocation breakpoint in two unrelated Tourette syndrome cases, within a region previously linked to the disorder. Hum Genet. 2003;113:154–161
  76. Matsumoto N, David DE, Johnson EW, Konecki D, Burmester JK, Ledbetter DH, et al. Breakpoint sequences of an 1;8 translocation in a family with Gilles de la Tourette syndrome. Eur J Hum Genet. 2000;8:875–883
  77. Donnai D. Gene location in Tourette syndrome. Lancet. 1987;1:627
  78. State MW, Greally JM, Cuker A, Bowers PN, Henegariu O, Morgan TM, et al. Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype. Proc Natl Acad Sci U S A. 2003;100:4684–4689
  79. Cuker A, State MW, King RA, Davis N, Ward DC. Candidate locus for Gilles de la Tourette syndrome/obsessive compulsive disorder/chronic tic disorder at 18q22. Am J Med Genet A. 2004;130A:37–39
  80. Verkerk AJ, Mathews CA, Joosse M, Eussen BH, Heutink P, Oostra BA. CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics. 2003;82:1–9
  81. Belloso JM, Bache I, Guitart M, Caballin MR, Halgren C, Kirchhoff M, et al. Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome. Eur J Hum Genet. 2007;15:711–713
  82. Taylor LD, Krizman DB, Jankovic J, Hayani A, Steuber PC, Greenberg F, et al. 9p Monosomy in a patient with Gilles de la Tourette's syndrome. Neurology. 1991;41:1513–1515
  83. Singh DN, Howe GL, Jordan HW, Hara S. Tourette's syndrome in a black woman with associated triple X and 9p mosaicism. J Natl Med Assoc. 1982;74:675–682
  84. Brett PM, Curtis D, Robertson MM, Gurling HM. The genetic susceptibility to Gilles de la Tourette syndrome in a large multiple affected British kindred: linkage analysis excludes a role for the genes coding for dopamine D1, D2, D3, D4, D5 receptors, dopamine beta hydroxylase, tyrosinase, and tyrosine hydroxylase. Biol Psychiatry. 1995;37:533–540
  85. Gelernter J, Kennedy JL, Grandy DK, Zhou QY, Civelli O, Pauls DL, et al Exclusion of close linkage of Tourette's syndrome to D1 dopamine receptor. Am J Psychiatry. 1993;150:449–453
  86. Thompson M, Comings DE, Feder L, George SR, O'Dowd BF. Mutation screening of the dopamine D1 receptor gene in Tourette's syndrome and alcohol dependent patients. Am J Med Genet. 1998;81:241–244
  87. Chou IC, Tsai CH, Lee CC, Kuo HT, Hsu YA, Li CI, et al. Association analysis between Tourette's syndrome and dopamine D1 receptor gene in Taiwanese children. Psychiatr Genet. 2004;14:219–221
  88. Tarnok Z, Ronai Z, Gervai J, Kereszturi E, Gadoros J, Sasvari-Szekely M, et al. Dopaminergic candidate genes in Tourette syndrome: association between tic severity and 3′ UTR polymorphism of the dopamine transporter gene. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:900–905
  89. Devor EJ, Grandy DK, Civelli O, Litt M, Burgess AK, Isenberg KE, et al. Genetic linkage is excluded for the D2-dopamine receptor lambda HD2G1 and flanking loci on chromosome 11q22-q23 in Tourette syndrome. Hum Hered. 1990;40:105–108
  90. Gelernter J, Pakstis AJ, Pauls DL, Kurlan R, Gancher ST, Civelli O, et al. Gilles de la Tourette syndrome is not linked to D2-dopamine receptor. Arch Gen Psychiatry. 1990;47:1073–1077
  91. Gelernter J, Pauls DL, Leckman J, Kidd KK, Kurlan R. D2 dopamine receptor alleles do not influence severity of Tourette's syndrome. Results from four large kindreds. Arch Neurol. 1994;51:397–400
  92. Diaz-Anzaldua A, Joober R, Riviere JB, Dion Y, Lesperance P, Richer F, et al. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol Psychiatry. 2004;9:272–277
  93. Nothen MM, Hebebrand J, Knapp M, Hebebrand K, Camps A, von Gontard A, et al Association analysis of the dopamine D2 receptor gene in Tourette's syndrome using the haplotype relative risk method. Am J Med Genet. 1994;54:249–252
  94. Comings DE, Comings BG, Muhleman D, Dietz G, Shahbahrami B, Tast D, et al The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991;266:1793–1800
  95. Comings DE, Wu S, Chiu C, Ring RH, Gade R, Ahn C, et al. Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes—DRD2, D beta H, and DAT1. Am J Med Genet. 1996;67:264–288
  96. Devor EJ. The D2 dopamine receptor and Tourette's syndrome. JAMA. 1992;267:651;author reply 652
  97. Lee CC, Chou IC, Tsai CH, Wang TR, Li TC, Tsai FJ. Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome. Pediatr Neurol. 2005;33:272–276
  98. Brett P, Robertson M, Gurling H, Curtis D. Failure to find linkage and increased homozygosity for the dopamine D3 receptor gene in Tourette's syndrome. Lancet. 1993;341:1225
  99. Devor EJ, Dill-Devor RM, Magee HJ. The Bal I and Msp I polymorphisms in the dopamine D3 receptor gene display, linkage disequilibrium with each other but no association with Tourette syndrome. Psychiatr Genet. 1998;8:49–52
  100. Hebebrand J, Nothen MM, Lehmkuhl G, Poustka F, Schmidt M, Propping P, et al. Tourette's syndrome and homozygosity for the dopamine D3 receptor gene. German Tourette's Syndrome Collaborative Research Group. Lancet. 1993;341:1483–1484
  101. Comings DE, Muhleman D, Dietz G, Dino M, LeGro R, Gade R. Association between Tourette's syndrome and homozygosity at the dopamine D3 receptor gene. Lancet. 1993;341:906
  102. Barr CL, Wigg KG, Zovko E, Sandor P, Tsui LC. No evidence for a major gene effect of the dopamine D4 receptor gene in the susceptibility to Gilles de la Tourette syndrome in five Canadian families. Am J Med Genet. 1996;67:301–305
  103. Comings DE, Gonzalez N, Wu S, Gade R, Muhleman D, Saucier G, et al. Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse. Am J Med Genet. 1999;88:358–368
  104. Hebebrand J, Nothen MM, Ziegler A, Klug B, Neidt H, Eggermann K, et al. Nonreplication of linkage disequilibrium between the dopamine D4 receptor locus and Tourette syndrome. Am J Hum Genet. 1997;61:238–239
  105. Cruz C, Camarena B, King N, Paez F, Sidenberg D, de la Fuente JR, et al. Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics. Neurosci Lett. 1997;231:1–4
  106. Grice DE, Leckman JF, Pauls DL, Kurlan R, Kidd KK, Pakstis AJ, et al. Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test. Am J Hum Genet. 1996;59:644–652
  107. Barr CL, Wigg KG, Zovko E, Sandor P, Tsui LC. Linkage study of the dopamine D5 receptor gene and Gilles de la Tourette syndrome. Am J Med Genet. 1997;74:58–61
  108. Ozbay F, Wigg KG, Turanli ET, Asherson P, Yazgan Y, Sandor P, et al. Analysis of the dopamine beta hydroxylase gene in Gilles de la Tourette syndrome. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:673–677
  109. Gelernter J, Vandenbergh D, Kruger SD, Pauls DL, Kurlan R, Pakstis AJ, et al. The dopamine transporter protein gene (SLC6A3): primary linkage mapping and linkage studies in Tourette syndrome. Genomics. 1995;30:459–463
  110. Vandenbergh DJ, Thompson MD, Cook EH, Bendahhou E, Nguyen T, Krasowski MD, et al. Human dopamine transporter gene: coding region conservation among normal, Tourette's disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol Psychiatry. 2000;5:283–292
  111. Yoon DY, Rippel CA, Kobets AJ, Morris CM, Lee JE, Williams PN, et al. Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3). Am J Med Genet B Neuropsychiatr Genet. 2007;144B:605–610
  112. Rowe DC, Stever C, Gard JM, Cleveland HH, Sanders ML, Abramowitz A, et al. The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behav Genet. 1998;28:215–225
  113. Gade R, Muhleman D, Blake H, MacMurray J, Johnson P, Verde R, et al. Correlation of length of VNTR alleles at the X-linked MAOA gene and phenotypic effect in Tourette syndrome and drug abuse. Mol Psychiatry. 1998;3:50–60
  114. Barr CL, Wigg KG, Sandor P. Catechol-O-methyltransferase and Gilles de la Tourette syndrome. Mol Psychiatry. 1999;4:492–495
  115. Cavallini MC, Di Bella D, Catalano M, Bellodi L. An association study between 5-HTTLPR polymorphism, COMT polymorphism, and Tourette's syndrome. Psychiatry Res. 2000;97:93–100
  116. Xu C, Ozbay F, Wigg K, Shulman R, Tahir E, Yazgan Y, et al. Evaluation of the genes for the adrenergic receptors alpha 2A and alpha 1C and Gilles de la Tourette Syndrome. Am J Med Genet B Neuropsychiatr Genet. 2003;119B:54–59
  117. Chou IC, Tsai CH, Wan L, Hsu YA, Tsai FJ. Association study between Tourette's syndrome and polymorphisms of noradrenergic genes (ADRA2A, ADRA2C). Psychiatr Genet. 2007;17:359
  118. Stober G, Hebebrand J, Cichon S, Bruss M, Bonisch H, Lehmkuhl G, et al. Tourette syndrome and the norepinephrine transporter gene: results of a systematic mutation screening. Am J Med Genet. 1999;88:158–163
  119. Rippel CA, Kobets AJ, Yoon DY, Williams PN, Shugart YY, Bridges DD, et al. Norepinephrine transporter polymorphisms in Tourette syndrome with and without attention deficit hyperactivity disorder: no evidence for significant association. Psychiatr Genet. 2006;16:179–180
  120. Brett PM, Curtis D, Robertson MM, Gurling HM. Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol Psychiatry. 1997;42:941–947
  121. Brett PM, Curtis D, Robertson MM, Gurling HM. Exclusion of the 5-HT1A serotonin neuroreceptor and tryptophan oxygenase genes in a large British kindred multiply affected with Tourette's syndrome, chronic motor tics, and obsessive-compulsive behavior. Am J Psychiatry. 1995;152:437–440
  122. Erdmann J, Shimron-Abarbanell D, Cichon S, Albus M, Maier W, Lichtermann D, et al Systematic screening for mutations in the promoter and the coding region of the 5-HT1A gene. Am J Med Genet. 1995;60:393–399
  123. Huang Y, Liu X, Li T, Guo L, Sun X, Xiao X, et al. Cases-control association study and transmission disequilibrium test of T102C polymorphism in 5HT2A and Tourette syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2001;18:11–13
  124. Dickel DE, Veenstra-VanderWeele J, Bivens NC, Wu X, Fischer DJ, Van Etten-Lee M, et al. Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder. Biol Psychiatry. 2007;61:322–329
  125. Niesler B, Frank B, Hebebrand J, Rappold G. Serotonin receptor genes HTR3A and HTR3B are not involved in Gilles de la Tourette syndrome. Psychiatr Genet. 2005;15:303–304
  126. Gelernter J, Rao PA, Pauls DL, Hamblin MW, Sibley DR, Kidd KK. Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics. 1995;26:207–209
  127. Comings DE, Gade R, Muhleman D, Chiu C, Wu S, To M, et al. Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders. Pharmacogenetics. 1996;6:307–318
  128. Comings DE, Chen C, Wu S, Muhleman D. Association of the androgen receptor gene (AR) with ADHD and conduct disorder. NeuroReport. 1999;10:1589–1592
  129. Hebebrand J, Nothen MM, Klug B, Wettke-Schafer R, Camps A, Lisch S, et al No association between length of the (CAG)n repeat of the Huntington's disease gene and Tourette's syndrome. Biol Psychiatry. 1995;37:209–211
  130. Schoenian S, Konig I, Oertel W, Remschmidt H, Ziegler A, Hebebrand J, et al. HLA-DRB genotyping in Gilles de la Tourette patients and their parents. Am J Med Genet B Neuropsychiatr Genet. 2003;119B:60–64
  131. Huang Y, Li T, Wang Y, Ansar J, Lanting G, Liu X, et al. Linkage disequilibrium analysis of polymorphisms in the gene for myelin oligodendrocyte glycoprotein in Tourette's syndrome patients from a Chinese sample. Am J Med Genet B Neuropsychiatr Genet. 2004;124B:76–80
  132. Miranda DM, Wigg K, Feng Y, Sandor P, Barr CL. Association study between Gilles de la Tourette Syndrome and two genes in the Robo-Slit pathway located in the chromosome 11q24 linked/associated region. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:68–72
  133. Mossner R, Muller-Vahl KR, Doring N, Stuhrmann M. Role of the novel tryptophan hydroxylase-2 gene in Tourette syndrome. Mol Psychiatry. 2007;12:617–619
  134. Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science. 2008;322:881–888
  135. Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005;310:317–320
  136. Keen-Kim D, Mathews CA, Reus VI, Lowe TL, Herrera LD, Budman CL, et al. Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Hum Mol Genet. 2006;15:3324–3328
  137. Zuchner S, Cuccaro ML, Tran-Viet KN, Cope H, Krishnan RR, Pericak-Vance MA, et al. SLITRK1 mutations in trichotillomania. Mol Psychiatry. 2006;11:887–889
  138. Scharf JM, Moorjani P, Fagerness J, Platko JV, Illmann C, Galloway B, et al. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology. 2008;70(16 Pt 2):1495–1496
  139. Deng H, Le WD, Xie WJ, Jankovic J. Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome. Acta Neurol Scand. 2006;114:400–402
  140. Chou IC, Wan L, Liu SC, Tsai CH, Tsai FJ. Association of the Slit and Trk-like 1 gene in Taiwanese patients with Tourette syndrome. Pediatr Neurol. 2007;37:404–406
  141. Miranda DM, Wigg K, Kabia EM, Feng Y, Sandor P, Barr CL. Association of SLITRK1 to Gilles de la Tourette Syndrome. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:483–486
  142. Zimprich A, Hatala K, Riederer F, Stogmann E, Aschauer HN, Stamenkovic M. Sequence analysis of the complete SLITRK1 gene in Austrian patients with Tourette's disorder. Psychiatr Genet. 2008;18:308–309
  143. Verkerk AJ, Cath DC, van der Linde HC, Both J, Heutink P, Breedveld G, et al. Genetic and clinical analysis of a large Dutch Gilles de la Tourette family. Mol Psychiatry. 2006;11:954–964
  144. Wendland JR, Kruse MR, Murphy DL. Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive-compulsive disorder. Mol Psychiatry. 2006;11:802–804
  145. Fabbrini G, Pasquini M, Aurilia C, Berardelli I, Breedveld G, Oostra BA, et al. A large Italian family with Gilles de la Tourette syndrome: clinical study and analysis of the SLITRK1 gene. Mov Disord. 2007;22:2229–2234
  146. Orth M, Djarmati A, Baumer T, Winkler S, Grunewald A, Lohmann-Hedrich K, et al. Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene. Mov Disord. 2007;22:2090–2096
  147. Pasquini M, Fabbrini G, Berardelli I, Bonifati V, Biondi M, Berardelli A. Psychopathological features of obsessive-compulsive disorder in an Italian family with Gilles de la Tourette syndrome not linked to the SLITRK1 gene. Psychiatry Res. 2008;161:109–111
  148. Manolio TA, Brooks LD, Collins FS. A HapMap harvest of insights into the genetics of common disease. J Clin Invest. 2008;118:1590–1605
  149. McCarroll SA, Kuruvilla FG, Korn JM, Cawley S, Nemesh J, Wysoker A, et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet. 2008;40:1166–1174
  150. Wang K, Li M, Hadley D, Liu R, Glessner J, Grant SF, et al. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res. 2007;17:1665–1674
  151. Dudbridge F, Gusnanto A. Estimation of significance thresholds for genomewide association scans. Genet Epidemiol. 2008;32:227–234
  152. Purcell S, Cherny SS, Sham PC. Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics. 2003;19:149–150
  153. Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, et al. Complement factor H polymorphism in age-related macular degeneration. Science. 2005;308:385–389
  154. Gudbjartsson DF, Walters GB, Thorleifsson G, Stefansson H, Halldorsson BV, Zusmanovich P, et al. Many sequence variants affecting diversity of adult human height. Nat Genet. 2008;40:609–615
  155. Lettre G, Jackson AU, Gieger C, Schumacher FR, Berndt SI, Sanna S, et al. Identification of ten loci associated with height highlights new biological pathways in human growth. Nat Genet. 2008;40:584–591
  156. Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet. 2008;40:575–583
  157. Visscher PM. Sizing up human height variation. Nat Genet. 2008;40:489–490
  158. Reich DE, Lander ES. On the allelic spectrum of human disease. Trends Genet. 2001;17:502–510
  159. Pritchard JK. Are rare variants responsible for susceptibility to complex diseases?. Am J Hum Genet. 2001;69:124–137
  160. Xu Z, He Z, Huang K, Tang W, Li Z, Tang R, et al. No genetic association between NCAM1 gene polymorphisms and schizophrenia in the Chinese population. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1633–1636
  161. Ferreira MA, Sham P, Daly MJ, Purcell S. Ascertainment through family history of disease often decreases the power of family-based association studies. Behav Genet. 2007;37:631–636
  162. Sklar P, Smoller JW, Fan J, Ferreira MA, Perlis RH, Chambert K, et al. Whole-genome association study of bipolar disorder. Mol Psychiatry. 2008;13:558–569
  163. WTCCC, Consortium WTCC . Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661–678

☆ Supported in part by grants from the National Institute of Neurological Disease and Stroke, NS16648 and NS40024.

PII: S0022-3999(09)00258-X

doi: 10.1016/j.jpsychores.2009.06.006

Journal of Psychosomatic Research
Volume 67, Issue 6 , Pages 533-545 , December 2009

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