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The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders

  • J. D. Grant (a1), M. T. Lynskey (a2), P. A. F. Madden (a1), E. C. Nelson (a1), L. R. Few (a1), K. K. Bucholz (a1), D. J. Statham (a3), N. G. Martin (a4), A. C. Heath (a1) and A. Agrawal (a1)...

Abstract

Background.

Genetic influences contribute significantly to co-morbidity between conduct disorder and substance use disorders. Estimating the extent of overlap can assist in the development of phenotypes for genomic analyses.

Method.

Multivariate quantitative genetic analyses were conducted using data from 9577 individuals, including 3982 complete twin pairs and 1613 individuals whose co-twin was not interviewed (aged 24–37 years) from two Australian twin samples. Analyses examined the genetic correlation between alcohol dependence, nicotine dependence and cannabis abuse/dependence and the extent to which the correlations were attributable to genetic influences shared with conduct disorder.

Results.

Additive genetic (a2 = 0.48–0.65) and non-shared environmental factors explained variance in substance use disorders. Familial effects on conduct disorder were due to additive genetic (a2 = 0.39) and shared environmental (c2 = 0.15) factors. All substance use disorders were influenced by shared genetic factors (r g = 0.38–0.56), with all genetic overlap between substances attributable to genetic influences shared with conduct disorder. Genes influencing individual substance use disorders were also significant, explaining 40–73% of the genetic variance per substance.

Conclusions.

Among substance users in this sample, the well-documented clinical co-morbidity between conduct disorder and substance use disorders is primarily attributable to shared genetic liability. Interventions targeted at generally reducing deviant behaviors may address the risk posed by this shared genetic liability. However, there is also evidence for genetic and environmental influences specific to each substance. The identification of these substance-specific risk factors (as well as potential protective factors) is critical to the future development of targeted treatment protocols.

Copyright

Corresponding author

* Address for correspondence: Dr J. D. Grant, Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, CB 8134, St Louis, MO 63110, USA. (Email: grantj@psychiatry.wustl.edu)

References

Hide All
APA (1994). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Washington, DC.
Bierut, LJ, Goate, AM, Breslau, N, Johnson, EO, Bertelsen, S, Fox, L, Agrawal, A, Bucholz, KK, Grucza, R, Hesselbrock, V, Kramer, J, Kuperman, S, Nurnberger, J, Porjesz, B, Saccone, NL, Schuckit, M, Tischfield, J, Wang, JC, Foroud, T, Rice, JP, Edenberg, HJ (2012). ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry. Molecular Psychiatry 17, 445450.
Bucholz, KK, Cadoret, R, Cloninger, CR, Dinwiddie, SH, Hesselbrock, VM, Nurnberger, JI Jr., Reich, T, Schmidt, I, Schuckit, MA (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. Journal of Studies on Alcohol 55, 149158.
Button, TM, Hewitt, JK, Rhee, SH, Young, SE, Corley, RP, Stallings, MC (2006). Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence. Twin Research and Human Genetics 9, 3845.
Button, TM, Rhee, SH, Hewitt, JK, Young, SE, Corley, RP, Stallings, MC (2007). The role of conduct disorder in explaining the comorbidity between alcohol and illicit drug dependence in adolescence. Drug and Alcohol Dependence 87, 4653.
Fu, Q, Heath, AC, Bucholz, KK, Nelson, E, Goldberg, J, Lyons, MJ, True, WR, Jacob, T, Tsuang, MT, Eisen, SA (2002). Shared genetic risk of major depression, alcohol dependence, and marijuana dependence: contribution of antisocial personality disorder in men. Archives of General Psychiatry 59, 11251132.
Gelernter, J, Kranzler, HR, Sherva, R, Almasy, L, Koesterer, R, Smith, AH, Anton, R, Preuss, UW, Ridinger, M, Rujescu, D, Wodarz, N, Zill, P, Zhao, H, Farrer, LA (2014). Genome-wide association study of alcohol dependence: significant findings in African- and European-Americans including novel risk loci. Molecular Psychiatry 19, 4149.
Heath, AC, Bucholz, KK, Madden, PAF, Dinwiddie, SH, Slutske, WS, Bierut, LJ, Statham, DJ, Dunne, MP, Whitfield, JB, Martin, NG (1997). Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychological Medicine 27, 13811396.
Heath, AC, Martin, NG, Lynskey, MT, Todorov, AA, Madden, PAF (2002). Estimating two-stage models for genetic influences on alcohol, tobacco or drug use initiation and dependence vulnerability in twin and family data. Twin Research 5, 113124.
Hicks, BM, Schalet, BD, Malone, SM, Iacono, WG, McGue, M (2011). Psychometric and genetic architecture of substance use disorder and behavioral disinhibition measures for gene association studies. Behavior Genetics 41, 459475.
Iacono, WG, Carlson, SR, Taylor, J, Elkins, IJ, McGue, M (1999). Behavioral disinhibition and the development of substance-use disorders: findings from the Minnesota Twin Family Study. Development and Psychopathology 11, 869900.
Kendler, KS, Aggen, SH, Prescott, CA, Crabbe, J, Neale, MC (2012). Evidence for multiple genetic factors underlying the DSM-IV criteria for alcohol dependence. Molecular Psychiatry 17, 13061315.
Kendler, KS, Jacobson, KC, Prescott, CA, Neale, MC (2003 a). Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. American Journal of Psychiatry 160, 687695.
Kendler, KS, Myers, J, Prescott, CA (2007). Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Archives of General Psychiatry 64, 13131320.
Kendler, KS, Neale, MC, Sullivan, P, Corey, LA, Gardner, CO, Prescott, CA (1999). A population-based twin study in women of smoking initiation and nicotine dependence. Psychological Medicine 29, 299308.
Kendler, KS, Prescott, CA, Myers, J, Neale, MC (2003 b). The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60, 929937.
Kendler, KS, Schmitt, E, Aggen, SH, Prescott, CA (2008). Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Archives of General Psychiatry 65, 674682.
Knopik, VS, Heath, AC, Madden, PAF, Bucholz, KK, Slutske, WS, Nelson, EC, Statham, D, Whitfield, JB, Martin, NG (2004). Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors. Psychological Medicine 34, 15191530.
Krueger, RF, Hicks, BM, Patrick, CJ, Carlson, SR, Iacono, WG, McGue, M (2002). Etiologic connections among substance dependence, antisocial behavior, and personality: modeling the externalizing spectrum. Journal of Abnormal Psychology 111, 411424.
Liu, JZ, Tozzi, F, Waterworth, DM, Pillai, SG, Muglia, P, Middleton, L, Berrettini, W, Knouff, CW, Yuan, X, Waeber, G, Vollenweider, P, Preisig, M, Wareham, NJ, Zhao, JH, Loos, RJF, Barroso, I, Khaw, KT, Grundy, S, Barter, P, Mahley, R, Kesaniemi, A, McPherson, R, Vincent, JB, Strauss, J, Kennedy, JL, Farmer, A, McGuffin, P, Day, R, Matthews, K, Bakke, P, Gulsvik, A, Lucae, S, Ising, M, Brueckl, T, Horstmann, S, Wichmann, HE, Rawal, R, Dahmen, N, Lamina, C, Polasek, O, Zgaga, L, Huffman, J, Campbell, S, Kooner, J, Chambers, JC, Burnett, MS, Devaney, JM, Pichard, AD, Kent, KM, Satler, L, Lindsay, JM, Waksman, R, Epstein, S, Wilson, JF, Wild, SH, Campbell, H, Vitart, V, Reilly, MP, Li, M, Qu, L, Wilensky, R, Matthai, W, Hakonarson, HH, Rader, DJ, Franke, A, Wittig, M, Schafer, A, Uda, M, Terracciano, A, Xiao, X, Busonero, F, Scheet, P, Schlessinger, D, St Clair, D, Rujescu, D, Abecasis, GR, Grabe, HJ, Teumer, A, Volzke, H, Petersmann, A, John, U, Rudan, I, Hayward, C, Wright, AF, Kolcic, I, Wright, BJ, Thompson, JR, Balmforth, AJ, Hall, AS, Samani, NJ, Anderson, CA, Ahmad, T, Mathew, CG, Parkes, M, Satsangi, J, Caulfield, M, Munroe, PB, Farrall, M, Dominiczak, A, Worthington, J, Thomson, W, Eyre, S, Barton, A, The Wellcome Trust Case Control Consortium, Mooser, V, Francks, C, Marchini, J (2010). Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics 42, 436440.
Lynskey, MT, Agrawal, A, Henders, AK, Nelson, EC, Madden, PAF, Martin, NG (2012). An Australian twin study of cannabis and other illicit drug use and misuse, and other psychopathology. Twin Research and Human Genetics 15, 631641.
Lynskey, MT, Heath, AC, Nelson, EC, Bucholz, KK, Madden, PAF, Slutske, WS, Statham, DJ, Martin, NG (2002). Genetic and environmental contributions to cannabis dependence in a national young adult twin sample. Psychological Medicine 32, 195207.
Maciejewski, DF, Creemers, HE, Lynskey, MT, Madden, PAF, Heath, AC, Statham, DJ, Martin, NG, Verweij, KJH (2014). Overlapping genetic and environmental influences on nonsuicidal self-injury and suicidal ideation: different outcomes, same etiology? JAMA Psychiatry 71, 699705.
McGue, M, Zhang, Y, Miller, MB, Basu, S, Vrieze, S, Hicks, B, Malone, S, Oetting, WS, Iacono, WG (2013). A genome-wide association study of behavioral disinhibition. Behavior Genetics 43, 363373.
Medland, SE, Nyholt, DR, Painter, JN, McEvoy, BP, McRae, AF, Zhu, G, Gordon, SD, Ferreira, MA, Wright, MJ, Henders, AK, Campbell, MJ, Duffy, DL, Hansell, NK, Macgregor, S, Slutske, WS, Heath, AC, Montgomery, GW, Martin, NG (2009). Common variants in the trichohyalin gene are associated with straight hair in Europeans. American Journal of Human Genetics 85, 750755.
Neale, MC (2004). Statistical Modeling with Mx. Department of Psychiatry, Box #980710: Richmond, VA 23298.
Neale, MC, Cardon, LR (1992). Methodology for Genetic Studies of Twins and Families. Kluwer Academic Publishers: The Netherlands.
Neale, MC, Harvey, E, Maes, HH, Sullivan, PF, Kendler, KS (2006). Extensions to the modeling of initiation and progression: applications to substance use and abuse. Behavior Genetics 36, 507524.
Palmer, RH, Young, SE, Corley, RP, Hopfer, CJ, Stallings, MC, Hewitt, JK (2013). Stability and change of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis DSM-IV dependence symptoms. Behavior Genetics 43, 374385.
Rhee, SH, Hewitt, JK, Young, SE, Corley, RP, Crowley, TJ, Neale, MC, Stallings, MC (2006). Comorbidity between alcohol dependence and illicit drug dependence in adolescents with antisocial behavior and matched controls. Drug and Alcohol Dependence 84, 8592.
Rice, JP, Hartz, SM, Agrawal, A, Almasy, L, Bennett, S, Breslau, N, Bucholz, KK, Doheny, KF, Edenberg, HJ, Goate, AM, Hesselbrock, V, Howells, WB, Johnson, EO, Kramer, J, Krueger, RF, Kuperman, S, Laurie, C, Manolio, TA, Neuman, RJ, Nurnberger, JI, Porjesz, B, Pugh, E, Ramos, EM, Saccone, N, Saccone, S, Schuckit, M, Bierut, LJ (2012). CHRNB3 is more strongly associated with Fagerstrom test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results. Addiction 107, 20192028.
Rose, RJ, Dick, DM, Viken, RJ, Pulkkinen, L, Kaprio, J (2004). Genetic and environmental effects on conduct disorder and alcohol dependence symptoms and their covariation at age 14. Alcoholism, Clinical and Experimental Reearch 28, 15411548.
Sartor, CE, Grant, JD, Bucholz, KK, Madden, PAF, Heath, AC, Agrawal, A, Whitfield, JB, Statham, DJ, Martin, NG, Lynskey, MT (2010). Common genetic contributions to alcohol and cannabis use and dependence symptomatology. Alcoholism, Clinical Experimental Research 34, 545554.
SAS Institute, Inc (2002–2008). SAS User's Guide, Version 9.2. SAS Institute Inc: Cary, NC.
Thomasson, HR, Crabb, DW, Edenberg, HJ, Li, TK (1993). Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behavior Genetics 23, 131136.
Thorgeirsson, TE, Gudbjartsson, DF, Surakka, I, Vink, JM, Amin, N, Geller, F, Sulem, P, Rafnar, T, Esko, T, Walter, S, Gieger, C, Rawal, R, Mangino, M, Prokopenko, I, Magi, R, Keskitalo, K, Gudjonsdottir, IH, Gretarsdottir, S, Stefansson, H, Thompson, JR, Aulchenko, YS, Nelis, M, Aben, KK, den Heijer, M, Dirksen, A, Ashraf, H, Soranzo, N, Valdes, AM, Steves, C, Uitterlinden, AG, Hofman, A, Tonjes, A, Kovacs, P, Hottenga, JJ, Willemsen, G, Vogelzangs, N, Doring, A, Dahmen, N, Nitz, B, Pergadia, ML, Saez, B, De Diego, V, Lezcano, V, Garcia-Prats, MD, Ripatti, S, Perola, M, Kettunen, J, Hartikainen, AL, Pouta, A, Laitinen, J, Isohanni, M, Huei-Yi, S, Allen, M, Krestyaninova, M, Hall, AS, Jones, GT, van Rij, AM, Mueller, T, Dieplinger, B, Haltmayer, M, Jonsson, S, Matthiasson, SE, Oskarsson, H, Tyrfingsson, T, Kiemeney, LA, Mayordomo, JI, Lindholt, JS, Pedersen, JH, Franklin, WA, Wolf, H, Montgomery, GW, Heath, AC, Martin, NG, Madden, PAF, Giegling, I, Rujescu, D, Jarvelin, MR, Salomaa, V, Stumvoll, M, Spector, TD, Wichmann, HE, Metspalu, A, Samani, NJ, Penninx, BW, Oostra, BA, Boomsma, DI, Tiemeier, H, van Duijn, CM, Kaprio, J, Gulcher, JR, The ENGAGE Consortium, McCarthy, MI, Peltonen, L, Thorsteinsdottir, U, Stefansson, K (2010). Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. Nature Genetics 42, 448453.
Tobacco and Genetics Consortium (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics 42, 441447.
Vrieze, SI, Feng, S, Miller, MB, Hicks, BM, Pankratz, N, Abecasis, GR, Iacono, WG, McGue, M (2014). Rare nonsynonymous exonic variants in addiction and behavioral disinhibition. Biological Psychiatry 75, 783789.
Vrieze, SI, Hicks, BM, Iacono, WG, McGue, M (2012). Decline in genetic influence on the co-occurrence of alcohol, marijuana, and nicotine dependence symptoms from age 14 to 29. American Journal of Psychiatry 169, 10731081.
Vrieze, SI, McGue, M, Miller, MB, Hicks, BM, Iacono, WG (2013). Three mutually informative ways to understand the genetic relationships among behavioral disinhibition, alcohol use, drug use, nicotine use/dependence, and their co-occurrence: twin biometry, GCTA, and genome-wide scoring. Behavior Genetics 43, 97107.
Wetherill, L, Agrawal, A, Kapoor, M, Bertelsen, S, Bierut, LJ, Brooks, A, Dick, D, Hesselbrock, M, Hesselbrock, V, Koller, DL, Le, N, Nurnberger, JI Jr., Salvatore, JE, Schuckit, M, Tischfield, JA, Wang, JC, Xuei, X, Edenberg, HJ, Porjesz, B, Bucholz, K, Goate, AM, Foroud, T (2015). Association of substance dependence phenotypes in the COGA sample. Addiction Biology 20, 617627.
Xian, H, Scherrer, JF, Grant, JD, Eisen, SA, True, WR, Jacob, T, Bucholz, KK (2008). Genetic and environmental contributions to nicotine, alcohol and cannabis dependence in male twins. Addiction 103, 13911398.
Young, SE, Rhee, SH, Stallings, MC, Corley, RP, Hewitt, JK (2006). Genetic and environmental vulnerabilities underlying adolescent substance use and problem use: general or specific? Behavior Genetics 36, 603615.

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The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders

  • J. D. Grant (a1), M. T. Lynskey (a2), P. A. F. Madden (a1), E. C. Nelson (a1), L. R. Few (a1), K. K. Bucholz (a1), D. J. Statham (a3), N. G. Martin (a4), A. C. Heath (a1) and A. Agrawal (a1)...

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