The Genetics of Obsessive‐Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway‐Based Approach for Gene Discovery

Journal of the American Academy of Child and Adolescent Psychiatry

Volumn 49, Issue 8, 2010, Pages 810-819.e2

  Grados, Marco A ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Genetics; Genome wide association studies; Obsessive compulsive disorder; Pedigrees; Tourette syndrome

Indexed keywords

AMINE OXIDASE (FLAVIN CONTAINING); AMPA RECEPTOR; BRAIN DERIVED NEUROTROPHIC FACTOR; DOPAMINE 1 RECEPTOR; DOPAMINE 4 RECEPTOR; DOPAMINE TRANSPORTER; EXCITATORY AMINO ACID TRANSPORTER 3; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; PHOSPHATIDYLINOSITOL 3 KINASE; TRANSCRIPTION FACTOR 7 LIKE 2;

ATTENTION DEFICIT DISORDER; BACTERIAL ARTIFICIAL CHROMOSOME; BIOINFORMATICS; DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS; DNA STRUCTURE; GENE MAPPING; GENE SEQUENCE; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENETICS; GILLES DE LA TOURETTE SYNDROME; HUMAN; NERVE CELL DIFFERENTIATION; NONHUMAN; OBSESSIVE COMPULSIVE DISORDER; PEDIGREE; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOLESCENT; ANIMALS; CHILD; COMORBIDITY; CROSS-SECTIONAL STUDIES; DISEASE MODELS, ANIMAL; GENETIC ASSOCIATION STUDIES; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; OBSESSIVE-COMPULSIVE DISORDER; PHENOTYPE; TOURETTE SYNDROME;

EID: 77955717820     PISSN: 08908567     EISSN: 15275418     Source Type: Journal    
DOI: 10.1016/j.jaac.2010.04.009     Document Type: Review

References (103)

1. Leckman JF, Grice DE, Barr LC, et al. Tic-related vs. non-tic-related obsessive compulsive disorder. Anxiety 1994;1:208-215.
2. Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. Neurology 2001;57:1383-1388.
3. Leckman JF, Walker DE, Goodman WK, Pauls DL, Cohen DJ. “Just right” perceptions associated with compulsive behavior in Tourette’s syndrome. Am J Psychiatry 1994;151:675-680.
4. Miguel EC, Baer L, Coffey BJ, et al. Phenomenological differences appearing with repetitive behaviours in obsessive-compulsive disorder and Gilles de la Tourette’s syndrome. Br J Psychiatry 1997;170:140-145.
5. 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.
6. Grados MA, Riddle MA, Samuels JF, 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.
7. Pauls DL, Leckman JF, Towbin KE, Zahner GE, Cohen DJ. A possible genetic relationship exists between Tourette’s syndrome and obsessive-compulsive disorder. Psychopharmacol Bull 1986;22:730-733.
8. Miguel EC, Leckman JF, Rauch S, et al. Obsessive-compulsive disorder phenotypes: implications for genetic studies. Mol Psychiatry 2005;10:258-275.
9. Pinto A, Greenberg BD, Grados MA, et al. Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories. Psychiatry Res 2008;160:83-93.
10. Saxena S, Brody AL, Maidment KM, et al. Cerebral glucose metabolism in obsessive-compulsive hoarding. Am J Psychiatry 2004;161:1038-1048.
11. Mataix-Cols D, Wooderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML. Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. Arch Gen Psychiatry 2004;61:564-576.
12. Mathews CA, Jang KL, Herrera LD, et al. Tic symptom profiles in subjects with Tourette Syndrome from two genetically isolated populations. Biol Psychiatry 2007;61:292-300.
13. Alsobrook JP, Pauls DL. A factor analysis of tic symptoms in Gilles de la Tourette’s syndrome. Am J Psychiatry 2002;159:291-296.
14. 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.
15. Nestadt G, Di CZ, Riddle MA, et al. Obsessive-compulsive disorder: subclassification based on co-morbidity. Psychol Med 2009;39:1491-1501.
16. Grados M, Kazman J, Heley K, Fox J, Kitamura C. A Latent Class Analysis of Pediatric OCD using Tics, ADHD, Depression and Anxiety. Boston, MA: Annual Meeting of the American Academy of Child and Adolescent Psychiatry; October 28 - November 2, 2008.
17. 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.
18. Hudziak JJ, Althoff RR, Derks EM, Faraone SV, Boomsma DI. Prevalence and genetic architecture of Child Behavior Checklist-juvenile bipolar disorder. Biol Psychiatry 58:562-568.
19. Zielasek J, Gaebel W. Modern modularity and the road towards a modular psychiatry. Eur Arch Psychiatry Clin Neurosci 2008;258(Suppl):60-65.
20. Beesdo K, Lau JY, Guyer AE, et al. Common and distinct amygdala-function perturbations in depressed vs anxious adolescents. Arch Gen Psychiatry 2009;66:275-285.
21. Menzies L, Achard S, Chamberlain SR, et al. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain 2007;130:3223-3236.
22. Hudziak JJ, Van Beijsterveldt CE, Althoff RR, et al. Genetic and environmental contributions to the Child Behavior Checklist Obsessive-Compulsive Scale: a cross-cultural twin study. Arch Gen Psychiatry 2004;61:608-616.
23. Crosbie J, Perusse D, Barr CL, Schachar RJ. Validating psychiatric endophenotypes: inhibitory control and attention deficit hyperactivity disorder. Neurosci Biobehav Rev 2008;32:40-55.
24. Rosenberg DR, Averbach DH, O’Hearn KM, Seymour AB, Birmaher B, Sweeney JA. Oculomotor response inhibition abnormalities in pediatric obsessive-compulsive disorder. Arch Gen Psychiatry 1997;54:831-838.
25. Menzies L, Achard S, Chamberlain SR, et al. Neurocognitive endophenotypes of obsessive-compulsive disorder. Brain 2007;130:3223-3236.
26. Bevan MD, Atherton JF, Baufreton J. Cellular principles underlying normal and pathological activity in the subthalamic nucleus. Curr Opin Neurobiol 2006;16:621-628.
27. Chamberlain SR, Menzies L, Hampshire A, et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science 2008;321:421-422.
28. Greisberg S, McKay D. Neuropsychology of obsessive-compulsive disorder: a review and treatment implications. Clin Psychol Rev 2003;23:95-117.
29. Church JA, Wenger KK, Dosenbach NU, Miezin FM, Petersen SE, Schlaggar BL. Task control signals in pediatric Tourette syndrome show evidence of immature and anomalous functional activity. Front Hum Neurosci 2009;3:1-14.
30. Hanna GL, Himle JA, Curtis GC, Gillespie BW. A family study of obsessive-compulsive disorder with pediatric probands. Am J Med Genet B Neuropsychiatr Genet 2005;134B:13-19.
31. do Rosario-Campos MC, Leckman JF, Curi M, et al. A family study of early-onset obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2005;136B:92-97.
32. Schork NJ, Murray SS, Frazer KA, Topol EJ. Common vs. rare allele hypotheses for complex diseases. Curr Opin Genet Dev 2009;19:212-219.
33. Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 2008;40:695-701.
34. Grados MA, Walkup JT. A new gene for Tourette’s syndrome: a window into causal mechanisms?. Trends Genet 2006;22:291-293.
35. Cunninghame Graham DS. Genome-wide association studies in systemic lupus erythematosus: a perspective. Arthritis Res Ther 2009;11:119.
36. Ferreira MA, O’Donovan MC, Meng YA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008;40:1056-1058.
37. Weedon MN, Lango H, Lindgren CM, et al. Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 2008;40:575-583.
38. Saxena R, Voight BF, Lyssenko V, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007;316:1331-1336.
39. Moore AF, Jablonski KA, McAteer JB, et al. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes 2008;57:2503-2510.
40. Goldstein DB. Common genetic variation and human traits. N Engl J Med 2009;360:1696-1698.
41. Greer JM, Capecchi MR. Hoxb8 is required for normal grooming behavior in mice. Neuron 2002;33:23-34.
42. Zuchner S, Wendland JR, Ashley-Koch AE, et al. Multiple rare SAPAP3 missense variants in trichotillomania and OCD. Mol Psychiatry 2009;14:6-9.
43. Bienvenu OJ, Wang Y, Shugart YY, et al. Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet 2009;150B:710-720.
44. Abelson JF, Kwan KY, O’Roak BJ, et al. Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 2005;310:317-320.
45. Scharf JM, Moorjani P, Fagerness J, et al. Lack of association between SLITRK1var321 and Tourette syndrome in a large family-based sample. Neurology 2008;70:1495-1496.
46. Zimprich A, Hatala K, Riederer F, et al. Sequence analysis of the complete SLITRK1 gene in Austrian patients with Tourette’s disorder. Psychiatr Genet 2008;18:308-309.
47. Katayama K, Yamada K, Ornthanalai VG, et al. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities. Mol Psychiatry 2010;15:177-184.
48. Shearin AL, Ostrander EA. Leading the way: canine models of genomics and disease. Dis Model Mech 2010;3:27-34.
49. Rapoport JL, Ryland DH, Kriete M. Drug treatment of canine acral lick. An animal model of obsessive-compulsive disorder. Arch Gen Psychiatry 1992;49:517-521.
50. Pauls DL. An update on the genetics of Gilles de la Tourette syndrome. J Psychosom Res 2003;55:7-12.
51. Grados M, Wilcox HC. Genetics of obsessive-compulsive disorder: a research update. Expert Rev Neurother 2007;7:967-980.
52. Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder.
53. McDougle CJ, Epperson CN, Price LH, Gelernter J. Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder. Mol Psychiatry 1998;3:270-273.
54. Hu XZ, Lipsky RH, Zhu G, et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 2006;78:815-826.
55. Ozaki N, Goldman D, Kaye WH, et al. Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. Mol Psychiatry 2003;8:933-936.
56. Delorme R, Betancur C, Wagner M, et al. Support for the association between the rare functional variant I425V of the serotonin transporter gene and susceptibility to obsessive compulsive disorder. Mol Psychiatry 2005;10:1059-1061.
57. Mundo E, Richter MA, Zai G, et al. 5HT1Dbeta receptor gene implicated in the pathogenesis of obsessive-compulsive disorder: further evidence from a family-based association study. Mol Psychiatry 2002;7:805-809.
58. Cruz C, Camarena B, King N, Paez F, Sidenberg D, de IF Jr., Nicolini H. 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.
59. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.
60. Hemmings SM, Kinnear CJ, Lochner C, et al. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates. Psychiatry Res 2004;128:175-182.
61. Karayiorgou M, Altemus M, Galke BL, et al. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder. Proc Natl Acad Sci U S A 1997;94:4572-4575.
62. Pooley EC, Fineberg N, Harrison PJ. The met(158) allele of catechol-O-methyltransferase (COMT) is associated with obsessive-compulsive disorder in men: case-control study and meta-analysis. Mol Psychiatry 2007;12:556-561.
63. Hall D, Dhilla A, Charalambous A, Gogos JA, Karayiorgou M. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 2003;73:370-376.
64. Yoon DY, Rippel CA, Kobets AJ, et al. Dopaminergic polymorphisms in Tourette syndrome: association with the DAT gene (SLC6A3). Am J Med Genet B Neuropsychiatr Genet 2007;144B:605-610.
65. Grice DE, Leckman JF, Pauls DL, 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.
66. The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD).
67. Hasler G, Kazuba D, Murphy DL. Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism. Am J Med Genet B Neuropsychiatr Genet 2006;141:403-408.
68. Hanna GL, Veenstra-VanderWeele J, Cox NJ, et al. Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet 2002;114:541-552.
69. Hanna GL, Veenstra-VanderWeele J, Cox NJ, et al. Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder. Biol Psychiatry 2007;62:856-862.
70. Shugart YY, Samuels J, Willour VL, et al. Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Mol Psychiatry 2006;11:763-770.
71. 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.
72. Knight S, Coon H, Johnson M, Leppert MF, Camp NJ, McMahon WM. Linkage analysis of Tourette syndrome in a large Utah pedigree. Am J Med Genet B Neuropsychiatr Genet 2010;153B:656-662.
73. Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 2006;63:769-776.
74. Wang Y, Samuels JF, Chang YC, et al. Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families. Am J Med Genet B Neuropsychiatr Genet 2009;150B:33-40.
75. Samuels J, Shugart YY, Grados MA, et al. Significant Linkage to Compulsive Hoarding on Chromosome 14 in Families with Obsessive-Compulsive Disorder: Results From the OCD Collaborative Genetics Study. Am J Psychiatry 2007;164:493-499.
76. Willour VL, Yao SY, Samuels J, et al. Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet 2004;75:508-513.
77. Dickel DE, Veenstra-VanderWeele J, Cox NJ, et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry 2006;63:778-785.
78. Stewart SE, Fagerness JA, Platko J, et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2007;144B:1027-1033.
79. Shugart YY, Wang Y, Samuels JF, et al. A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet 2009;150B:886-892.
80. Wang Y, Adamczyk A, Shugart YY, et al. A screen of SLC1A1 for OCD-related alleles. Am J Med Genet B Neuropsychiatr Genet 2010;153B:675-679.
81. Nieoullon A, Canolle B, Masmejean F, Guillet B, Pisano P, Lortet S. The neuronal excitatory amino acid transporter EAAC1/EAAT3: does it represent a major actor at the brain excitatory synapse?. J Neurochem 2006;98:1007-1018.
82. Kwon CH, Luikart BW, Powell CM, et al. Pten regulates neuronal arborization and social interaction in mice. Neuron 2006;50:377-388.
83. Li D, He L. Association study between the NMDA receptor 2B subunit gene (GRIN2B) and schizophrenia: a HuGE review and meta-analysis. Genet Med 2007;9:4-8.
84. Avramopoulos D, Lasseter VK, Fallin MD, et al. Stage II follow-up on a linkage scan for bipolar disorder in the Ashkenazim provides suggestive evidence for chromosome 12p and the GRIN2B gene. Genet Med 2007;9:745-751.
85. Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy JL, Richter MA. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Psychopharmacology (Berl) 2004;174:530-538.
86. Arnold PD, Macmaster FP, Richter MA, et al. Glutamate receptor gene (GRIN2B) associated with reduced anterior cingulate glutamatergic concentration in pediatric obsessive-compulsive disorder. Psychiatry Res 2009;172:136-139.
87. Menuz K, O’Brien JL, Karmizadegan S, Bredt DS, Nicoll RA. TARP redundancy is critical for maintaining AMPA receptor function. J Neurosci 2008;28:8740-8746.
88. Hafler BP, Choi MY, Shivdasani RA, Rowitch DH. Expression and function of Nkx6.3 in vertebrate hindbrain. Brain Res 2008;1222:42-50.
89. Mendoza-Topaz C, Urra F, Barria R, et al. DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function. J Neurosci 2008;28:304-314.
90. Bentley DR. Whole-genome re-sequencing. Curr Opin Genet Dev 2006;16:545-552.
91. Waxman EA, Baconguis I, Lynch DR, Robinson MB. N-methyl-D-aspartate receptor-dependent regulation of the glutamate transporter excitatory amino acid carrier 1. J Biol Chem 2007;282:17594-17607.
92. Collins MO, Husi H, Yu L, et al. Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J Neurochem 2006;97(Suppl 1):16-23.
93. Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG. Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat Neurosci 2000;3:661-669.
94. Schmitz Y, Luccarelli J, Kim M, Wang M, Sulzer D. Glutamate controls growth rate and branching of dopaminergic axons. J Neurosci 2009;29:11973-11981.
95. Pickel VM, Colago EE, Mania I, Molosh AI, Rainnie DG. Dopamine D1 receptors co-distribute with N-methyl-D-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl-D-aspartic acid currents in rat basolateral amygdala. Neuroscience 2006;142:671-690.
96. Torkamani A, Topol EJ, Schork NJ. Pathway analysis of seven common diseases assessed by genome-wide association. Genomics 2008;92:265-272.
97. Torkamani A, Schork NJ. Pathway and network analysis with high-density allelic association data. Methods Mol Biol 2009;563:289-301.
98. Elbers CC, van Eijk KR, Franke L, et al. Using genome-wide pathway analysis to unravel the etiology of complex diseases. Genet Epidemiol 2009;33:419-431.
99. McPherson JD, Marra M, Hillier L, et al. A physical map of the human genome. Nature 2001;409:934-941.
100. Mardis ER. Next-generation DNA sequencing methods. Annu Rev Genomics Hum Genet 2008;9:387-402.
101. Ren B, Robert F, Wyrick JJ, et al. Genome-wide location and function of DNA binding proteins. Science 2000;290:2306-2309.
102. Johnson SM, Tan FJ, McCullough HL, Riordan DP, Fire AZ. Flexibility and constraint in the nucleosome core landscape of Caenorhabditis elegans chromatin. Genome Res 2006;16:1505-1516.
103. Mikkelsen TS, Ku M, Jaffe DB, et al. Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 2007;448:553-560.