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A genome-wide screen for genes influencing conduct disorder

Abstract

While behavioral genetic studies have suggested that childhood conduct disorder is under genetic influence, studies aimed at gene identification are lacking. This study represents the first genome-wide linkage analysis directed toward identifying genes contributing to conduct disorder. Genome screens of retrospectively reported childhood conduct disorder and conduct disorder symptomatology were carried out in the genetically informative adult sample collected as part of the Collaborative Study on the Genetics of Alcoholism (COGA). The results suggest that regions on chromosomes 19 and 2 may contain genes conferring risk to conduct disorder. Interestingly, the same region on chromosome 2 has also been linked to alcohol dependence in this sample. Childhood conduct disorder is known to be associated with the susceptibility for future alcohol problems. Taken together, these findings suggest that some of the genes contributing to alcohol dependence in adulthood may also contribute to conduct disorder in childhood.

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References

  1. Diagnostic and Statistical Manual of Mental Disorders. 4th edn. 1994, American Psychiatric Association: Washington, DC.

  2. Kuperman S, Schlosser SS, Kramer JR, Bucholz KK, Hesselbrock V, Reich T, et al. Risk domains associated with an adolescent alcohol dependence diagnosis. Addiction 2001; 96: 629–636.

    Article  CAS  PubMed  Google Scholar 

  3. Moss HB, Lynch KG . Comorbid disruptive behavior disorder symptoms and their relationship to adolescent alcohol use disorders. Drug Alcohol Dependence 2001; 64: 75–83.

    Article  CAS  PubMed  Google Scholar 

  4. Molina BSG, Bukstein OG, Lynch KG . Attention-deficit/hyperactivity disorder and conduct disorder symptomatology in adolescents with alcohol use disorder. Psychol Addictive Behav 2002; 16: 161–164.

    Article  Google Scholar 

  5. Kuperman S, Schlosser SS, Kramer JR, Bucholz KK, Hesselbrock V, Reich T, et al. Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence. Am J Psychiatry 2001; 158: 2022–2026.

    Article  CAS  PubMed  Google Scholar 

  6. Crowley TJ, Milkulich SK, MacDonald M, Young SE, Zerbe GO . Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome. Drug Alcohol Dependence 1998; 49: 225–237.

    Article  CAS  PubMed  Google Scholar 

  7. Patterson GR, DeBaryshe BD, Ramsey E . A developmental perspective on antisocial behavior. Am Psychol 1989; 44: 329–335.

    Article  CAS  PubMed  Google Scholar 

  8. Emery RE . Interparental conflict and the children of discord and divorce. Psychol Bull 1982; 92: 310–330.

    Article  CAS  PubMed  Google Scholar 

  9. Frick PJ, Lahey BB, Loeber R, Stouthamer-Loeber M, Christ MA, Hanson K . Familial risk factors to oppositional defiant disorder and conduct disorder: parental psychopathology and maternal parenting. J Consult Clin Psychol 1992; 60: 49–55.

    Article  CAS  PubMed  Google Scholar 

  10. Bassarath L . Conduct disorder: a biopsychosocial review. Can J Psychiatry 2001; 46: 609–616.

    Article  CAS  PubMed  Google Scholar 

  11. Meyer JM, Rutter M, Silberg JL, Maes HH, Simonoff E, Shillady L et al. Familial aggregation for conduct disorder symptomatology: the role of genes, marital discord, and family adaptability. Psycho Med 2000; 30: 759–774.

    Article  CAS  Google Scholar 

  12. Slutske WS, Heath AC, Dinwiddie SH, Madden PAF, Bucholz KK, Dunne MP et al. Modeling genetic and environmental influences in the etiology of conduct disorder: a study of 2,682 adult twin pairs. J Abnormal Psychol 1997; 106: 266–279.

    Article  CAS  Google Scholar 

  13. Goldstein RB, Prescott C, Kendler KS . Genetic and environmental factors in conduct problems and adult antisocial behavior among adult female twins. J Nerv Ment Dis 2001; 189: 201–209.

    Article  CAS  PubMed  Google Scholar 

  14. Dick DM, Viken RJ, Kaprio J, Pulkkinen L, Nurnberger Jr JI, Rose RJ . Adolescent alcohol use and conduct disorder: Age 14 interview data from finnish twin STUDIES. Annual Meeting of the Behavior Genetics Association; 2002; Keystone, CO.

    Google Scholar 

  15. Rhee SH, Waldman I . Genetic and environmental influences on antisocial behavior: A meta-analysis of twin and adoption studies. Psychol Bull 2002; 128: 490–529.

    Article  PubMed  Google Scholar 

  16. True WR, Heath AC, Scherrer JF, Xian H, Lin N, Eisen SA et al. Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms. Am J Med Genet (Neuropsychiatr Genet) 1999; 88: 391–397.

    Article  CAS  Google Scholar 

  17. Heath AC . Genetic influences on drinking behavior n humans, In: Begleiter H, Kissn B, (eds). The Genetics of Alcoholism, Oxford University Press: New York. 1995, pp 82–121.

    Google Scholar 

  18. Miles DR, Stallings MC, Young SE, Hewitt JK, Crowley TJ, Fulker DW . A family history and direct interview study of the familial aggregation of substance abuse: the adolescent substance abuse study. Drug Alcohol Dependence 1998; 49: 105–114.

    Article  CAS  PubMed  Google Scholar 

  19. Slutske WS, Heath AC, Dinwiddle SH, Madden PAF, Bucholz KK, Dunne MP et al. Common genetic risk factors for conduct disorder and alcohol dependence. J Abnormal Psychol 1998; 107: 363–374.

    Article  CAS  Google Scholar 

  20. Feighner JP, Robins E, Guze SB, Woodruff RA, Winokur G, Munoz R . Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 1972; 26: 57–63.

    Article  CAS  PubMed  Google Scholar 

  21. Begleiter H, Reich T, Hesselbrock V, Porjesz B, Li TK, Schuckit M et al. The Collaborative Study on the Genetics of Alcoholism. Alcohol Health Res World 1995; 19: 228–236.

    Google Scholar 

  22. Bucholz KK, Cadoret R, Cloninger CR, Dinwiddie SH, Hesselbrock VM, Nurnberger JI et al. A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J Stud Alcohol 1994; 55: 149–158.

    Article  CAS  PubMed  Google Scholar 

  23. Hesselbrock M, Easton C, Bucholz KK, Schuckit M, Hesselbrock V . A validity study of the SSAGA–A comparison with the SCAN. Addiction 1999; 94: 1361–1370.

    Article  CAS  PubMed  Google Scholar 

  24. Bucholz KK, Hesselbrock V, Shayka JJ, Nurnberger Jr JI, Schuckit M, Reich T . Reliability of individual diagnostic criterion items for psychoactive substance dependence and impact on diagnosis. J Stud Alcohol 1995; 56: 500–505.

    Article  CAS  PubMed  Google Scholar 

  25. Foroud T, Edenberg HJ, Goate A, Rice J, Flury L, Koller DL et al. Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping. Alcoholism: Clin Exp Res 2000; 24: 933–945.

    Article  CAS  Google Scholar 

  26. Reich T, Edenberg HJ, Goate A, Williams JT, Rice JP, Van Eerdewegh P et al. Genome-wide search for genes affecting the risk for alcohol dependence. Am J Med Genet 1998; 81: 207–215.

    Article  CAS  PubMed  Google Scholar 

  27. Green PH . Documentation for CRIMAP, version 2.4. 1990.

  28. Boehnke M . Allele frequency estimation from pedigree data. Am J Hum Genet 1991; 48: 22–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hinds D, Risch N . The ASPEX package: Affected sib-pair exclusion mapping. 1999.

  30. Kruglyak L, Lander ES . Complete multipoint sib-pair analysis of qualitative and quantitative traits. Am J Human Genet 1995; 57: 439–454.

    CAS  Google Scholar 

  31. Lander E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1995; 11: 241–247.

    Article  CAS  PubMed  Google Scholar 

  32. Risch N . Linkage strategies for genetically complex traits. II. The power of affected relative pairs. Am J Human Genet 1990; 46: 229–251.

    CAS  Google Scholar 

  33. Hesselbrock V, Dick DM, Hesselbrock M, Foroud T, Schuckit M . The search for genetic risk factors associated with suicidal behavior. Alcoholism: Clinical and Experimental Research 2003, in press.

  34. 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 Human Genet 2002; 70: 1183–1196.

    Article  CAS  Google Scholar 

  35. Smalley SL, Kustanovich V, Minassian SL, Stone JL, Ogdie MN, McGough JJ et al. Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, a region implicated in autism. Am J Human Genet 2002; 71: 959–963.

    Article  Google Scholar 

  36. Rowe DC, Stever C, Chase D, Sherman S, Abramowitz A, Waldman I . Two dopamine genes related to reports of childhood retrospective inattention and conduct disorder symptoms. Mol Psychiatry 2001; 6: 429–433.

    Article  CAS  PubMed  Google Scholar 

  37. Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Blake H et al. Multivariate analysis of associations of 42 genes in ADHD, ODD, and conduct disorder. Clin Genet 2000; 58: 31–40.

    Article  CAS  PubMed  Google Scholar 

  38. Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Blake H et al. Comparison of the role of dopamine, serotonin, and noradrenaline genes in ADHD, ODD, and conduct disorder: multivariate regression analysis of 20 genes. Clin Genet 2000; 57: 178–196.

    Article  CAS  PubMed  Google Scholar 

  39. Eaves LJ, Rutter M, Silberg JL, Shillady L, Maes HH, Pickles A . Genetic and environmental causes of covariation in interview assessments of distruptive behavior in child and adolescent twins. Behav Genet 2000; 30: 321–334.

    Article  CAS  PubMed  Google Scholar 

  40. Burt SA, Krueger RF, McGue M, Iacono WG . Sources of covariation among attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder: The importance of shared environment. J Abnormal Psychol 2001; 110: 516–525.

    Article  Google Scholar 

Download references

Acknowledgements

The Collaborative Study on the Genetics of Alcoholism (COGA) (H Begleiter, SUNY HSCB, Principal Investigator; T Reich, Washington University, Co-Principal Investigator) includes eight different centers where data collection, analysis and/or storage takes place. The eight sites and Principal Investigator and Co-Investigators are: Indiana University (T-K Li, J Nurnberger Jr, PM Conneally, HJ Edenberg); University of Iowa (R Crowe, S Kuperman); University of California at San Diego (M Schuckit); University of Connecticut (V Hesselbrock); State University of New York, Health Sciences Center at Brooklyn (B Porjesz, H Begleiter); Washington University in St Louis (T Reich, CR Cloninger, J Rice, A Goate); Rutgers University (J Tischfield); and Southwest Foundation (L Almasy). This national collaborative study is supported by the NIH Grant U10AA08403 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Preparation of this manuscript was also supported by AA13358 (D Dick), K02-AA00285 (T Foroud), and MO1 RR6192 (V Hesselbrock).

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Correspondence to T Foroud.

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Dick, D., Li, TK., Edenberg, H. et al. A genome-wide screen for genes influencing conduct disorder. Mol Psychiatry 9, 81–86 (2004). https://doi.org/10.1038/sj.mp.4001368

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