Skip to main content

Twin Studies of Substance Use

  • Chapter
  • First Online:
Genetics of Substance Use

Abstract

The advent of molecular genetics might seem to have reduced the importance of twin studies, but in many ways, their utility has greatly increased instead. We first clarify the motivations for twin studies – to identify the origins of individual differences, with a view to using this information to better understand complex traits, and to improve the prevention and treatment disorders such as substance abuse. The chapter continues with a conceptual overview of the association between phenotypic similarity and genetic similarity and continues to describe the specification of a structural equation model for the simple additive genetic, common environment, and specific environment (ACE) model for data collected from pairs of twins reared together. Especially important in studies of substance use is the joint modeling of initiation and progression, to control for the lack of data on liability to addiction among those who do not initiate. The proxy information obtained from pairs of twins concordant vs. discordant for initiation enables identification of a submodel of the bivariate ACE model. We continue to show how multivariate twin data provide an opportunity to reject certain simple causal hypotheses for the covariation between complex traits. Following a description of statistical considerations, the third section describes some of the empirical findings to date on nicotine dependence. Finally, we discuss several future directions for substance use research, particularly those employing hybrid methodologies of molecular genetics and twin research, which enable assumption testing and improved causal inference.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Polderman TJ, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, et al. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet. 2015;47(7):702–9.

    Article  CAS  PubMed  Google Scholar 

  2. Jonsson H, Magnusdottir E, Eggertsson HP, Stefansson OA, Arnadottir GA, Eiriksson O, et al. Differences between germline genomes of monozygotic twins. Nat Genet. 2021;53(1):27–34.

    Article  CAS  PubMed  Google Scholar 

  3. Neale MC, Lubke G, Aggen SH, Dolan CV. Problems with using sum scores for estimating variance components: contamination and measurement non-invariance. Twin Res Hum Genet. 2005;8(6):553–68.

    Article  PubMed  Google Scholar 

  4. Neale MC, Eaves LJ. Estimating and controlling for the effects of volunteer bias with pairs of relatives. Behav Genet. 1993;23(3):271–7.

    Article  CAS  PubMed  Google Scholar 

  5. Fanelli D. Opinion: is science really facing a reproducibility crisis, and do we need it to? Proc Natl Acad Sci U S A. 2018;115(11):2628–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. McArdle JJ, McDonald RP. Some algebraic properties of the reticular action model for moment structures. Br J Math Stat Psychol. 1984;37:234–51.

    Article  PubMed  Google Scholar 

  7. von Oertzen T, Brandmaier AM, Tsang S. Structural equation modeling with Ωnyx. Struct Equ Model Multidiscip J. 2015;22(1):148–61.

    Article  Google Scholar 

  8. Verhulst B, Prom-Wormley E, Keller M, Medland S, Neale MC. Type I error rates and parameter bias in multivariate behavioral genetic models. Behav Genet. 2019;49(1):99–111.

    Article  PubMed  Google Scholar 

  9. Foley DL, Neale MC, Kendler KS. A longitudinal study of stressful life events assessed at interview with an epidemiological sample of adult twins: the basis of individual variation in event exposure. Psychol Med. 1996;26(6):1239–52.

    Article  CAS  PubMed  Google Scholar 

  10. Gillespie NA, Neale MC, Kendler KS. Pathways to cannabis abuse: a multi-stage model from cannabis availability, cannabis initiation and progression to abuse. Addiction. 2009;104(3):430–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PA, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16(1):36–49.

    Article  CAS  PubMed  Google Scholar 

  12. Kendler KS, Chen X, Dick D, Maes H, Gillespie N, Neale MC, et al. Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci. 2012;15(2):181–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Heath AC, Kessler RC, Neale MC, Hewitt JK, Eaves LJ, Kendler KS. Testing hypotheses about direction of causation using cross-sectional family data. Behav Genet. 1993;23(1):29–50.

    Article  CAS  PubMed  Google Scholar 

  14. Heath AC, Martin NG. Genetic models for the natural history of smoking: evidence for a genetic influence on smoking persistence. Addict Behav. 1993;18(1):19–34.

    Article  CAS  PubMed  Google Scholar 

  15. Kendler KS, Neale MC, Sullivan P, Corey LA, Gardner CO, Prescott CA. A population-based twin study in women of smoking initiation and nicotine dependence. Psychol Med. 1999;29(2):299–308.

    Article  CAS  PubMed  Google Scholar 

  16. Neale MC, Harvey E, Maes HH, Sullivan PF, Kendler KS. Extensions to the modeling of initiation and progression: applications to substance use and abuse. Behav Genet. 2006;36(4):507–24.

    Article  PubMed  Google Scholar 

  17. Boker S, Neale M, Maes H, Wilde M, Spiegel M, Brick T, et al. OpenMx: an open source extended structural equation modeling framework. Psychometrika. 2011;76(2):306–17.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Neale MC, Hunter MD, Pritikin JN, Zahery M, Brick TR, Kirkpatrick RM, et al. OpenMx 2.0: extended structural equation and statistical modeling. Psychometrika. 2016;81(2):535–49.

    Article  PubMed  Google Scholar 

  19. Steiger JH, Shapiro A, Browne MW. On the multivariate asymptotic distribution of sequential chi-square statistics. Psychometrika. 1985;50:253–64.

    Article  Google Scholar 

  20. Treur JL, Verweij KJH, Abdellaoui A, Fedko IO, de Zeeuw EL, Ehli EA, et al. Testing familial transmission of smoking with two different research designs. Nicotine Tob Res. 2018;20(7):836–42.

    Article  PubMed  Google Scholar 

  21. Maes HH, Prom-Wormley E, Eaves LJ, Rhee SH, Hewitt JK, Young S, et al. A genetic epidemiological mega analysis of smoking initiation in adolescents. Nicotine Tob Res. 2017;19(4):401–9.

    PubMed  PubMed Central  Google Scholar 

  22. Verweij KJ, Zietsch BP, Lynskey MT, Medland SE, Neale MC, Martin NG, et al. Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies. Addiction. 2010;105(3):417–30.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Bergen SE, Gardner CO, Kendler KS. Age-related changes in heritability of behavioral phenotypes over adolescence and young adulthood: a meta-analysis. Twin Res Hum Genet. 2007;10(3):423–33.

    Article  PubMed  Google Scholar 

  24. Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat Rev Genet. 2005;6(7):521–32.

    Article  CAS  PubMed  Google Scholar 

  25. Bienvenu OJ, Davydow DS, Kendler KS. Psychiatric 'diseases' versus behavioral disorders and degree of genetic influence. Psychol Med. 2011;41(1):33–40.

    Article  CAS  PubMed  Google Scholar 

  26. Dash GF, Martin NG, Agrawal A, Lynskey MT, Slutske WS. Are prescription misuse and illicit drug use etiologically distinct? A genetically-informed analysis of opioids and stimulants. Psychol Med. 2021:1–8.

    Google Scholar 

  27. Gillespie NA, Bates TC, Hickie IB, Medland SE, Verhulst B, Kirkpatrick RM, et al. Genetic and environmental risk factors in the non-medical use of over-the-counter or prescribed analgesics, and their relationship to major classes of licit and illicit substance use and misuse in a population-based sample of young adult twins. Addiction. 2019;114(12):2229–40.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kendler KS, Prescott CA. Genes, environment, and psychopathology: understanding the causes of psychiatric and substance use disorders. 1st ed. New York: The Guilford Press; 2006. 412 pp.

    Google Scholar 

  29. Kendler KS, Myers J, Prescott CA. Specificity of genetic and environmental risk factors for symptoms of cannabis, cocaine, alcohol, caffeine, and nicotine dependence. Arch Gen Psychiatry. 2007;64(11):1313–20.

    Article  PubMed  Google Scholar 

  30. Kendler KS, Prescott CA, Jacobson K, Myers J, Neale MC. The joint analysis of personal interview and family history diagnoses: evidence for validity of diagnosis and increased heritability estimates. Psychol Med. 2002;32(5):829–42.

    Article  CAS  PubMed  Google Scholar 

  31. Kendler KS, Schmitt E, Aggen SH, Prescott CA. Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry. 2008;65(6):674–82.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Dick DM, Meyers JL, Rose RJ, Kaprio J, Kendler KS. Measures of current alcohol consumption and problems: two independent twin studies suggest a complex genetic architecture. Alcohol Clin Exp Res. 2011;35(12):2152–61.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kendler KS, Jacobson KC, Prescott CA, Neale MC. Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins. Am J Psychiatry. 2003;160(4):687–95.

    Article  PubMed  Google Scholar 

  34. Tsuang MT, Lyons MJ, Meyer JM, Doyle T, Eisen SA, Goldberg J, et al. Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry. 1998;55(11):967–72.

    Article  CAS  PubMed  Google Scholar 

  35. Liu QR, Drgon T, Johnson C, Walther D, Hess J, Uhl GR. Addiction molecular genetics: 639,401 SNP whole genome association identifies many “cell adhesion” genes. Am J Med Genet B Neuropsychiatr Genet. 2006;141B(8):918–25.

    Article  CAS  PubMed  Google Scholar 

  36. Walters RK, Polimanti R, Johnson EC, McClintick JN, Adams MJ, Adkins AE, et al. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. Nat Neurosci. 2018;21(12):1656–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pasman JA, Verweij KJH, Gerring Z, Stringer S, Sanchez-Roige S, Treur JL, et al. GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nat Neurosci. 2018;21(9):1161–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu M, Jiang Y, Wedow R, Li Y, Brazel DM, Chen F, et al. Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nat Genet. 2019;51(2):237–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kendler KS, Lonn SL, Salvatore J, Sundquist J, Sundquist K. Divorce and the onset of alcohol use disorder: a Swedish population-based longitudinal cohort and co-relative study. Am J Psychiatry. 2017;174(5):451–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Waldron M, Heath AC, Lynskey MT, Bucholz KK, Madden PA, Martin NG. Alcoholic marriage: later start, sooner end. Alcohol Clin Exp Res. 2011;35(4):632–42.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Wichers M, Gillespie NA, Kendler KS. Genetic and environmental predictors of latent trajectories of alcohol use from adolescence to adulthood: a male twin study. Alcohol Clin Exp Res. 2013;37(3):498–506.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Olivares EL, Kendler KS, Neale MC, Gillespie NA. The genetic and environmental association between parental monitoring and risk of cannabis, stimulants, and cocaine initiation in a sample of male twins: does parenting matter? Twin Res Hum Genet. 2016;19(4):297–305.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Gillespie NA, Zhu G, Neale MC, Heath AC, Martin NG. Direction of causation modeling between cross-sectional measures of parenting and psychological distress in female twins. Behav Genet. 2003;33(4):383–96.

    Article  PubMed  Google Scholar 

  44. den Hoed M, Brage S, Zhao JH, Westgate K, Nessa A, Ekelund U, et al. Heritability of objectively assessed daily physical activity and sedentary behavior. Am J Clin Nutr. 2013;98(5):1317–25.

    Article  Google Scholar 

  45. Kendler KS, Myers J. A developmental twin study of church attendance and alcohol and nicotine consumption: a model for analyzing the changing impact of genes and environment. Am J Psychiatry. 2009;166(10):1150–5.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Button TM, Stallings MC, Rhee SH, Corley RP, Hewitt JK. The etiology of stability and change in religious values and religious attendance. Behav Genet. 2011;41(2):201–10.

    Article  PubMed  Google Scholar 

  47. Kendler KS, Baker JH. Genetic influences on measures of the environment: a systematic review. Psychol Med. 2007;37(5):615–26.

    Article  PubMed  Google Scholar 

  48. Kendler KS, Jacobson KC, Gardner CO, Gillespie N, Aggen SA, Prescott CA. Creating a social world: a developmental twin study of peer-group deviance. Arch Gen Psychiatry. 2007;64(8):958–65.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Gillespie NA, Neale MC, Jacobson K, Kendler KS. Modeling the genetic and environmental association between peer group deviance and cannabis use in male twins. Addiction. 2009;104(3):420–9.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mann FD, Patterson MW, Grotzinger AD, Kretsch N, Tackett JL, Tucker-Drob EM, et al. Sensation seeking, peer deviance, and genetic influences on adolescent delinquency: evidence for person-environment correlation and interaction. J Abnorm Psychol. 2016;125(5):679–91.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Vinkhuyzen AA, van der Sluis S, de Geus EJ, Boomsma DI, Posthuma D. Genetic influences on 'environmental' factors. Genes Brain Behav. 2010;9(3):276–87.

    Article  CAS  PubMed  Google Scholar 

  52. Dolan CV, de Kort JM, van Beijsterveldt TC, Bartels M, Boomsma DI. GE covariance through phenotype to environment transmission: an assessment in longitudinal twin data and application to childhood anxiety. Behav Genet. 2014;44(3):240–53.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Maes HH, Sullivan PF, Bulik CM, Neale MC, Prescott CA, Eaves LJ, et al. A twin study of genetic and environmental influences on tobacco initiation, regular tobacco use and nicotine dependence. Psychol Med. 2004;34(7):1251–61.

    Article  PubMed  Google Scholar 

  54. Kendler KS, Gardner CO Jr. Twin studies of adult psychiatric and substance dependence disorders: are they biased by differences in the environmental experiences of monozygotic and dizygotic twins in childhood and adolescence? Psychol Med. 1998;28(3):625–33.

    Article  CAS  PubMed  Google Scholar 

  55. Miles DR, van den Bree MB, Gupman AE, Newlin DB, Glantz MD, Pickens RW. A twin study on sensation seeking, risk taking behavior and marijuana use. Drug Alcohol Depend. 2001;62(1):57–68.

    Article  CAS  PubMed  Google Scholar 

  56. van den Bree MB, Johnson EO, Neale MC, Pickens RW. Genetic and environmental influences on drug use and abuse/dependence in male and female twins. Drug Alcohol Depend. 1998;52(3):231–41.

    Article  PubMed  Google Scholar 

  57. Rhee SH, Hewitt JK, Young SE, Corley RP, Crowley TJ, Stallings MC. Genetic and environmental influences on substance initiation, use, and problem use in adolescents. Arch Gen Psychiatry. 2003;60(12):1256–64.

    Article  PubMed  Google Scholar 

  58. Kendler KS, Karkowski LM, Neale MC, Prescott CA. Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Arch Gen Psychiatry. 2000;57(3):261–9.

    Article  CAS  PubMed  Google Scholar 

  59. McGue M, Elkins I, Iacono WG. Genetic and environmental influences on adolescent substance use and abuse. Am J Med Genet. 2000;96(5):671–7.

    Article  CAS  PubMed  Google Scholar 

  60. Agrawal A, Neale MC, Jacobson KC, Prescott CA, Kendler KS. Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach. Addict Behav. 2005;30(5):1043–8.

    Article  CAS  PubMed  Google Scholar 

  61. Krueger RF, Caspi A, Moffitt TE, Silva PA. The structure and stability of common mental disorders (DSM-III-R): a longitudinal-epidemiological study. J Abnorm Psychol. 1998;107(2):216–27.

    Article  CAS  PubMed  Google Scholar 

  62. Krueger RF. The structure of common mental disorders. Arch Gen Psychiatry. 1999;56(10):921–6.

    Article  CAS  PubMed  Google Scholar 

  63. Vollebergh WA, Iedema J, Bijl RV, de Graaf R, Smit F, Ormel J. The structure and stability of common mental disorders: the NEMESIS study. Arch Gen Psychiatry. 2001;58(6):597–603.

    Article  CAS  PubMed  Google Scholar 

  64. Krueger RF, Tackett JL. Personality and psychopathology: working toward the bigger picture. J Personal Disord. 2003;17(2):109–28.

    Article  Google Scholar 

  65. Eaton NR, Krueger RF, Keyes KM, Skodol AE, Markon KE, Grant BF, et al. Borderline personality disorder co-morbidity: relationship to the internalizing-externalizing structure of common mental disorders. Psychol Med. 2011;41(5):1041–50.

    Article  CAS  PubMed  Google Scholar 

  66. Kendler K, Aggen SH, Knudsen GP, Roysamb E, Neale MC, Reichborn-Kjennerud T. The structure of genetic and environmental risk factors for syndromal and subsyndromal common DSM-IV axis I and all axis II disorders. Am J Psychiatry. 2011;168(1):29–39.

    Article  PubMed  Google Scholar 

  67. Grove WM, Eckert ED, Heston L, Bouchard TJ Jr, Segal N, Lykken DT. Heritability of substance abuse and antisocial behavior: a study of monozygotic twins reared apart. Biol Psychiatry. 1990;27(12):1293–304.

    Article  CAS  PubMed  Google Scholar 

  68. Lyons MJ, True WR, Eisen SA, Goldberg J, Meyer JM, Faraone SV, et al. Differential heritability of adult and juvenile antisocial traits. Arch Gen Psychiatry. 1995;52(11):906–15.

    Article  CAS  PubMed  Google Scholar 

  69. 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. 1999;88(4):391–7.

    Article  CAS  PubMed  Google Scholar 

  70. Prom-Wormley E, Maes HHM, Schmitt JE, Panizzon MS, Xian H, Eyler LT, Franz CE, et al. Genetic and environmental contributions to the relationships between brain structure and average lifetime cigarette use. Behav Genet. 2015;45(2):157–70. (1573–3297 (Electronic)).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Gillespie NA, Neale MC, Bates TC, Eyler LT, Fennema-Notestine C, Vassileva J, et al. Testing associations between cannabis use and subcortical volumes in two large population-based samples. Addiction. 2018;

    Google Scholar 

  72. Wilson S, Malone SM, Thomas KM, Iacono WG. Adolescent drinking and brain morphometry: a co-twin control analysis. Dev Cogn Neurosci. 2015;16:130–8.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Sheerin CA-OX, Bustamante D, Bountress KE, Cusack SE, Aggen SH, Kendler KS, et al. Psychiatric resilience and alcohol resistance: a twin study of genetic correlation and sex differences. https://doi.org/10.1007/s10519-021-10059-7. (1573–3297 (Electronic)).

  74. Kendler KS, Lonn SL, Maes HH, Lichtenstein P, Sundquist J, Sundquist K. A Swedish population-based multivariate twin study of externalizing disorders. Behav Genet. 2016;46(2):183–92.

    Article  PubMed  Google Scholar 

  75. Neale MC, Cherny SS, Sham PC, Whitfield JB, Heath AC, Birley AC, et al. Distinguishing population stratification from genuine allelic effects with Mx: association of ADH2 with alcohol consumption. Behav Genet. 1999;29:233–44.

    Article  Google Scholar 

  76. Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA. Childhood sexual abuse and adult psychiatric and substance use disorders in women - an epidemiological and Cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953–9.

    Article  CAS  PubMed  Google Scholar 

  77. Kendler KS, Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler RC. Smoking and major depression. A causal analysis. Arch Gen Psychiatry. 1993;50(1):36–43.

    Article  CAS  PubMed  Google Scholar 

  78. Gillespie NA, Kendler KS. Use of genetically informed methods to clarify the nature of the association between cannabis use and risk for schizophrenia. JAMA Psychiat. 2021;78(5):467–8.

    Article  Google Scholar 

  79. Gillespie NA, Martin NG. Modeling direction of causation. In: Everitt N, Howell DC, editors. Encyclopedia of statistics in behavioral science. Chichester: Wiley; 2005. p. 496–9.

    Google Scholar 

  80. Yang J, Lee SH, Goddard ME, Visscher PM. GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet. 2011;88(1):76–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kirkpatrick RM, Pritikin JN, Hunter MD, Neale MC. Combining structural-equation modeling with genomic-relatedness-matrix restricted maximum likelihood in OpenMx. Behav Genet. 2021;51(3):331–42.

    Article  PubMed  Google Scholar 

  82. Hwang LD, Mitchell BL, Medland SE, Martin NG, Neale MC, Evans DA-O. The augmented classical twin design: incorporating genome-wide identity by descent sharing into twin studies in order to model violations of the equal environments assumption. Behav Genet. 2021;51(3):223–36. (1573–3297 (Electronic)).

    Article  PubMed  Google Scholar 

  83. Dolan CV, Huijskens RCA, Minică CC, Neale MC, Boomsma DI. Incorporating polygenic risk scores in the ACE twin model to estimate A-C covariance. Behav Genet. 2021;51(3):237–49. (1573–3297 (Electronic)).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Tamimy ZA-O, Kevenaar SA-O, Hottenga JA-O, Hunter MA-O, de Zeeuw EA-O, Neale MA-OX, et al. Multilevel twin models: geographical region as a third level variable. Behav Genet. 2021;51(3):319–30. (1573–3297 (Electronic)).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Maes HH, Prom-Wormley E, Eaves LJ, Rhee SH, Hewitt JK, Young S, et al. A genetic epidemiological mega analysis of smoking initiation in adolescents. Nicotine Tob Res. 2017;19(4):401–9. (1469–994X (Electronic)).

    PubMed  PubMed Central  Google Scholar 

  86. Minica CC, Dolan CV, Boomsma DI, de Geus E, Neale MC. Extending causality tests with genetic instruments: an integration of Mendelian randomization with the classical twin design. Behav Genet. 2018;48(4):337–49.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael C. Neale .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Neale, M.C., Bustamante, D., Zhou, Y., Gillespie, N.A. (2022). Twin Studies of Substance Use. In: Vanyukov, M.M. (eds) Genetics of Substance Use. Springer, Cham. https://doi.org/10.1007/978-3-030-95350-8_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-95350-8_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-95349-2

  • Online ISBN: 978-3-030-95350-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics