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Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5

Molecular Psychiatry volume 9, pages 711–717 (2004)Cite this article

Abstract

Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (χ2=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.

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References

  1. Scahill L, Schwab-Stone M . Epidemiology of ADHD in school-age children. Child Adolesc Psychiatr Clin N Am 2000; 9: 541–555, (vii).

    Article  CAS  PubMed  Google Scholar 

  2. Wilens TE, Biederman J, Spencer TJ . Attention deficit/hyperactivity disorder across the lifespan. Annu Rev Med 2002; 53: 113–131.

    Article  CAS  PubMed  Google Scholar 

  3. Association AP. Diagnostic and statistical manual of mental disorders, 4th ed. American Psychiatric Association: Washington, DC, 1994.

  4. Biederman J, Newcorn J, Sprich S . Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders. Am J Psychiatry 1991; 148: 564–577.

    Article  CAS  PubMed  Google Scholar 

  5. Bird HR, Gould MS, Staghezza BM . Patterns of diagnostic comorbidity in a community sample of children aged 9 through 16 years. J Am Acad Child Adolesc Psychiatry 1993; 32: 361–368.

    Article  CAS  PubMed  Google Scholar 

  6. Spencer T, Biederman J, Wilens T . Attention-deficit/hyperactivity disorder and comorbidity. Pediatr Clin N Am 1999; 46: 915–927, (vii).

    Article  CAS  Google Scholar 

  7. Faraone SV, Short EJ, Biederman J, Findling RL, Roe C, Manos MJ . Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug–placebo and drug–drug response curve analysis of a naturalistic study. Int J Neuropsychopharmacol 2002; 5: 121–129.

    Article  CAS  PubMed  Google Scholar 

  8. Coolidge FL, Thede LL, Young SE . Heritability and the comorbidity of attention deficit hyperactivity disorder with behavioral disorders and executive function deficits: a preliminary investigation. Dev Neuropsychol 2000; 17: 273–287.

    Article  CAS  PubMed  Google Scholar 

  9. Willerman L . Activity level and hyperactivity in twins. Child Dev 1973; 44: 288–293.

    Article  CAS  PubMed  Google Scholar 

  10. Goodman R, Stevenson J . A twin study of hyperactivity—II. The aetiological role of genes, family relationships and perinatal adversity. J Child Psychol Psychiatry 1989; 30: 691–709.

    Article  CAS  PubMed  Google Scholar 

  11. Faraone SV, Biederman J . Neurobiology of attention-deficit hyperactivity disorder. Biol Psychiatry 1998; 44: 951–958.

    Article  CAS  PubMed  Google Scholar 

  12. Rowe DC, den Oord EJ, Stever C, Giedinghagen LN, Gard JM, Cleveland HH et al. The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder. Mol Psychiatry 1999; 4: 580–586.

    Article  CAS  PubMed  Google Scholar 

  13. Todd RD, Lobos EA . Mutation screening of the dopamine D2 receptor gene in attention-deficit hyperactivity disorder subtypes: preliminary report of a research strategy. Am J Med Genet 2002; 114: 34–41.

    Article  PubMed  Google Scholar 

  14. Comings DE . Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. Ann NY Acad Sci 2001; 931: 50–83.

    Article  CAS  PubMed  Google Scholar 

  15. Barr CL, Wigg KG, Feng Y, Zai G, Malone M, Roberts W et al. Attention-deficit hyperactivity disorder and the gene for the dopamine D5 receptor. Mol Psychiatry 2000; 5: 548–551.

    Article  CAS  PubMed  Google Scholar 

  16. Daly G, Hawi Z, Fitzgerald M, Gill M . Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry 1999; 4: 192–196.

    Article  CAS  PubMed  Google Scholar 

  17. Payton A, Holmes J, Barrett JH, Hever T, Fitzpatrick H, Trumper AL et al. Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. Am J Med Genet 2001; 105: 464–470.

    Article  CAS  PubMed  Google Scholar 

  18. Tahir E, Yazgan Y, Cirakoglu B, Ozbay F, Waldman I, Asherson PJ . Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Mol Psychiatry 2000; 5: 396–404.

    Article  CAS  PubMed  Google Scholar 

  19. Meador-Woodruff JH, Damask SP, Wang J, Haroutunian V, Davis KL, Watson SJ . Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology 1996; 15: 17–29.

    Article  CAS  PubMed  Google Scholar 

  20. Rapport LJ, Van Voorhis A, Tzelepis A, Friedman SR . Executive functioning in adult attention-deficit hyperactivity disorder. Clin Neuropsychol 2001; 15: 479–491.

    Article  CAS  PubMed  Google Scholar 

  21. Lovejoy DW, Ball JD, Keats M, Stutts ML, Spain EH, Janda L et al. Neuropsychological performance of adults with attention deficit hyperactivity disorder (ADHD): diagnostic classification estimates for measures of frontal lobe/executive functioning. J Int Neuropsychol Soc 1999; 5: 222–233.

    Article  CAS  PubMed  Google Scholar 

  22. Rubia K, Overmeyer S, Taylor E, Brammer M, Williams SC, Simmons A et al. Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI. Neurosci Biobehav Rev 2000; 24: 13–19.

    Article  CAS  PubMed  Google Scholar 

  23. Smalley SL, Bailey JN, Palmer CG, Cantwell DP, McGough JJ, Del'Homme MA et al. Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder. Mol Psychiatry 1998; 3: 427–430.

    Article  CAS  PubMed  Google Scholar 

  24. LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N et al. Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1996; 1: 121–124.

    CAS  PubMed  Google Scholar 

  25. Rowe DC, Stever C, Giedinghagen LN, Gard JM, Cleveland HH, Terris ST et al. Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder. Mol Psychiatry 1998; 3: 419–426.

    Article  CAS  PubMed  Google Scholar 

  26. Swanson JM, Sunohara GA, Kennedy JL, Regino R, Fineberg E, Wigal T et al. Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry 1998; 3: 38–41.

    Article  CAS  PubMed  Google Scholar 

  27. Barr CL, Wigg KG, Bloom S, Schachar R, Tannock R, Roberts W et al. Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 2000; 96: 262–267.

    Article  CAS  PubMed  Google Scholar 

  28. Muglia P, Jain U, Macciardi F, Kennedy JL . Adult attention deficit hyperactivity disorder and the dopamine D4 receptor gene. Am J Med Genet 2000; 96: 273–277.

    Article  CAS  PubMed  Google Scholar 

  29. Faraone SV, Doyle AE, Mick E, Biederman J . Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 2001; 158: 1052–1057.

    Article  CAS  PubMed  Google Scholar 

  30. Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH . Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 1996; 12: 81–84.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 1996; 12: 78–80.

    Article  CAS  PubMed  Google Scholar 

  33. McCracken JT, Smalley SL, McGough JJ, Crawford L, Del'Homme M, Cantor RM et al. Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD). Mol Psychiatry 2000; 5: 531–536.

    Article  CAS  PubMed  Google Scholar 

  34. Barr CL, Feng Y, Wigg KG, Schachar R, Tannock R, Roberts W et al. 5′-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. Am J Med Genet 2001; 105: 84–90.

    Article  CAS  PubMed  Google Scholar 

  35. Castellanos FX, Lau E, Tayebi N, Lee P, Long RE, Giedd JN et al. Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses. Mol Psychiatry 1998; 3: 431–434.

    Article  CAS  PubMed  Google Scholar 

  36. Eisenberg J, Zohar A, Mei-Tal G, Steinberg A, Tartakovsky E, Gritsenko I et al. A haplotype relative risk study of the dopamine D4 receptor (DRD4) exon III repeat polymorphism and attention deficit hyperactivity disorder (ADHD). Am J Med Genet 2000; 96: 258–261.

    Article  CAS  PubMed  Google Scholar 

  37. Hawi Z, McCarron M, Kirley A, Daly G, Fitzgerald M, Gill M . No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population. Am J Med Genet 2000; 96: 268–272.

    Article  CAS  PubMed  Google Scholar 

  38. Kotler M, Manor I, Sever Y, Eisenberg J, Cohen H, Ebstein RP et al. Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. Am J Med Genet 2000; 96: 278–281.

    Article  CAS  PubMed  Google Scholar 

  39. Comings DE . Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. I. Drug abuse. Drug Alcohol Depend 1994; 35: 1–16.

    Article  CAS  PubMed  Google Scholar 

  40. Comings DE . Molecular heterosis as the explanation for the controversy about the effect of the DRD2 gene on dopamine D2 receptor density. Mol Psychiatry 1999; 4: 213–215.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. Kirley A, Hawi Z, Daly G, McCarron M, Mullins C, Millar N et al. Dopaminergic system genes in ADHD: toward a biological hypothesis. Neuropsychopharmacology 2002; 27: 607–619.

    CAS  PubMed  Google Scholar 

  43. Spielman RS, McGinnis RE, Ewens WJ . Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet 1993; 52: 506–516.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Maher BS, Marazita ML, Ferrell RE, Vanyukov MM . Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiatr Genet 2002; 12: 207–215.

    Article  PubMed  Google Scholar 

  45. Hawi Z, Lowe N, Kirley A, Gruenhage F, Nothen M, Greenwood T et al. Linkage disequilibrium mapping at DAT1, DRD5 and DBH narrows the search for ADHD susceptibility alleles at these loci. Mol Psychiatry 2003; 8: 299–308.

    Article  CAS  PubMed  Google Scholar 

  46. Cook Jr EH, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE et al. Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 1995; 56: 993–998.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Winsberg BG, Comings DE . Association of the dopamine transporter gene (DAT1) with poor methylphenidate response. J Am Acad Child Adolesc Psychiatry 1999; 38: 1474–1477.

    Article  CAS  PubMed  Google Scholar 

  48. Waldman ID, Rowe DC, Abramowitz A, Kozel ST, Mohr JH, Sherman SL et al. Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity. Am J Hum Genet 1998; 63: 1767–1776.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gill M, Daly G, Heron S, Hawi Z, Fitzgerald M . Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol Psychiatry 1997; 2: 311–313.

    Article  CAS  PubMed  Google Scholar 

  50. Todd RD, Jong YJ, Lobos EA, Reich W, Heath AC, Neuman RJ . No association of the dopamine transporter gene 3′ VNTR polymorphism with ADHD subtypes in a population sample of twins. Am J Med Genet 2001; 105: 745–748.

    Article  CAS  PubMed  Google Scholar 

  51. Palmer CG, Bailey JN, Ramsey C, Cantwell D, Sinsheimer JS, Del'Homme M et al. No evidence of linkage or linkage disequilibrium between DAT1 and attention deficit hyperactivity disorder in a large sample. Psychiatr Genet 1999; 9: 157–160.

    Article  CAS  PubMed  Google Scholar 

  52. Bakker SC, van der Meulen EM, Buitelaar JK, Sandkuijl LA, Pauls DL, Monsuur AJ et al. A whole genome scan in 164 Dutch sib pairs with attention-deficit hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q. Am J Hum Genet 2003; 72: 1251–1260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fisher SE, Francks C, McCracken JT, McGough JJ, Marlow AJ, MacPhie IL et al. A genomewide scan for loci involved in attention-deficit/hyperactivity disorder. Am J Hum Genet 2002; 70: 1183–1196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ogdie MN, Macphie IL, Minassian SL, Yang M, Fisher SE, Francks C et al. A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. Am J Hum Genet 2003; 72: 1268–1279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Risch N, Merikangas K . The future of genetic studies of complex human diseases. Science 1996; 273: 1516–1517.

    Article  CAS  PubMed  Google Scholar 

  56. Smalley SL, McGough JJ, Del'Homme M, NewDelman J, Gordon E, Kim T et al. Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2000; 39: 1135–1143.

    Article  CAS  PubMed  Google Scholar 

  57. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997; 36: 980–988.

    Article  CAS  PubMed  Google Scholar 

  58. Fyer AJ, Endicott J, Mannuza S, Klein DF . The Schedule for Affective Disorders and Schizophrenia-Lifetime Version, Modified for the Study of Anxiety Disorder 1985, Updated for DSM-IV (SADS-LA-IV). Anxiety Genetics Unit, New York State Psychiatric Institute: New York, 1995.

    Google Scholar 

  59. Hollingshead AB . Two Factor Index of Social Position. Yale University, Department of Sociology: New Haven, 1957.

    Google Scholar 

  60. Dietz G, Comings D . A simple restriction endonuclease based test for the dopamine D2 receptor gene (DRD2) haplotypes: linkage disequilibrium of the haplotypes with the Taq A1 allele. Psychiatr Genet 1997; 7: 133–135.

    Article  CAS  PubMed  Google Scholar 

  61. Lazzeroni LC, Lange K . A conditional inference framework for extending the transmission/disequilibrium test. Hum Hered 1998; 48: 67–81.

    Article  CAS  PubMed  Google Scholar 

  62. Lange K, Cantor R, Horvath S, Perola M, Sabatti C, Sinsheimer J et al. MENDEL Version 4.0: a complete package for the exact genetic analysis of discrete traits in pedigree and population data sets. Am J Hum Genet 2001; 69(Supplement): A1886.

    Google Scholar 

  63. SAS. SAS procedures guide for personal computers, 6.12 ed SAS Institute: Cary, NC, 1996.

  64. Ding YC, Chi HC, Grady DL, Morishima A, Kidd JR, Kidd KK et al. Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proc Natl Acad Sci USA 2002; 99: 309–314.

    Article  CAS  PubMed  Google Scholar 

  65. Barr CL, Xu C, Kroft J, Feng Y, Wigg K, Zai G et al. Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder. Biol Psychiatry 2001; 49: 333–339.

    Article  CAS  PubMed  Google Scholar 

  66. Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE . Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 1995; 5: 121–141.

    Article  CAS  PubMed  Google Scholar 

  67. Comings DE, Blum K . Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog Brain Res 2000; 126: 325–341.

    Article  CAS  PubMed  Google Scholar 

  68. Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Chen C et al. The additive effect of neurotransmitter genes in pathological gambling. Clin Genet 2001; 60: 107–116.

    Article  CAS  PubMed  Google Scholar 

  69. Sullivan MA, Rudnik-Levin F . Attention deficit/hyperactivity disorder and substance abuse. Diagnostic and therapeutic considerations. Ann NY Acad Sci 2001; 931: 251–270.

    Article  CAS  PubMed  Google Scholar 

  70. 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.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Institute of Mental Health Grants MH58277 (to SLS), MH01969 (to JJM), MH01805 (to JTM), and USPHS National Research Service Award GM07104 (to VK). Thanks to all the families who participated in this research and to Elva Rios, Tae Kim, Laura Combs, Leah Pressman, PhD, and Deborah Lynn, MD, for their help in data collection and to Dr Dennis Cantwell, who inspired our work on ADHD.

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  1. Department of Human Genetics, Division of Child and Adolescent Psychiatry, UCLA School of Medicine, University of California, Los Angeles, USA

    V Kustanovich, J Ishii, L Crawford & S F Nelson

  2. Division of Child and Adolescent Psychiatry, Center for Neurobehavioral Genetics, UCLA School of Medicine, University of California, Los Angeles, USA

    M Yang, J J McGough, J T McCracken, S L Smalley & S F Nelson

  3. Department of Psychiatry and Biobehavioral Sciences, Division of Child and Adolescent Psychiatry, UCLA School of Medicine, University of California, Los Angeles, USA

    J J McGough, J T McCracken, S L Smalley & S F Nelson

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  1. V Kustanovich
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Correspondence to S F Nelson.

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Kustanovich, V., Ishii, J., Crawford, L. et al. Transmission disequilibrium testing of dopamine-related candidate gene polymorphisms in ADHD: confirmation of association of ADHD with DRD4 and DRD5. Mol Psychiatry 9, 711–717 (2004). https://doi.org/10.1038/sj.mp.4001466

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