Original Article | Published:

Genetic predisposition to schizophrenia associated with increased use of cannabis

Molecular Psychiatry volume 19, pages 12011204 (2014) | Download Citation

Abstract

Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric disorder affecting ~1% of the population over their lifetime. Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. In a sample of 2082 healthy individuals, we show an association between an individual’s burden of schizophrenia risk alleles and use of cannabis. This was significant both for comparing those who have ever versus never used cannabis (P=2.6 × 104), and for quantity of use within users (P=3.0 × 10−3). Although directly predicting only a small amount of the variance in cannabis use, these findings suggest that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology. This form of gene–environment correlation is an important consideration when calculating the impact of environmental risk factors, including cannabis use.

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References

  1. 1.

    United Nations Office on Drugs and Crime. World Drug Report 2013. United Nations: New York, NY, USA, 2013.

  2. 2.

    , , . Cannabis use and misuse prevalence among people with psychosis. Br J Psychiatry 2005; 187: 306–313.

  3. 3.

    , , , , , et al. Cannabis and acute psychosis. Schizophr Res 1994; 13: 161–167.

  4. 4.

    . Cannabis and psychosis. Is there epidemiological evidence for an association?. Br J Psychiatry 1990; 157: 25–33.

  5. 5.

    , . Epidemiological analysis of alcohol and drug use as risk factors for psychotic experiences. J Nerv Ment Dis 1990; 178: 473–480.

  6. 6.

    , , , , , et al. The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: implications for psychosis. Neuropsychopharmacology 2004; 29: 1558–1572.

  7. 7.

    , , , , , et al. The acute effects of synthetic intravenous Delta9-tetrahydrocannabinol on psychosis, mood and cognitive functioning. Psychol Med 2009; 39: 1607–1616.

  8. 8.

    , , , , , . Cannabis use and psychosis: a longitudinal population-based study. Am J Epidemiol 2002; 156: 319–327.

  9. 9.

    , , , , , et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990; 264: 2511–2518.

  10. 10.

    , , , . Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry 2004; 184: 110–117.

  11. 11.

    , , , , , et al. Association between cannabis use and psychosis-related outcomes using sibling pair analysis in a cohort of young adults. Arch Gen Psychiatry 2010; 67: 440–447.

  12. 12.

    , , , , . Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 2002; 325: 1199.

  13. 13.

    , , , , , et al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 2005; 330: 11.

  14. 14.

    , , , , , et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370: 319–328.

  15. 15.

    , , , , , . Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 2002; 325: 1212–1213.

  16. 16.

    , , , , , et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–2196.

  17. 17.

    , . Reasons for substance use in schizophrenia. Acta Psychiatr Scand 1997; 96: 329–333.

  18. 18.

    , , . Motivations that maintain substance use among individuals with psychotic disorders. Schizophr Bull 2002; 28: 233–247.

  19. 19.

    , , , , , . Cannabis use predicts future psychotic symptoms, and vice versa. Addiction 2005; 100: 612–618.

  20. 20.

    , , . Tests of causal linkages between cannabis use and psychotic symptoms. Addiction 2005; 100: 354–366.

  21. 21.

    , , . Lower negative symptom scores among cannabis-dependent patients with schizophrenia-spectrum disorders: preliminary evidence from an African American first-episode sample. Schizophr Res 2004; 71: 61–64.

  22. 22.

    , . Influence of cannabis abuse on schizophrenic psychopathology. Acta Psychiatr Scand 1992; 85: 127–130.

  23. 23.

    , , , , . Drug abuse in schizophrenic patients: clinical correlates and reasons for use. Am J Psychiatry 1991; 148: 224–230.

  24. 24.

    , , , , . Gene-environment interplay between cannabis and psychosis. Schizophr Bull 2008; 34: 1111–1121.

  25. 25.

    , , . Schizophrenia as a complex trait—Evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003; 60: 1187–1192.

  26. 26.

    , , , , , et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969–976.

  27. 27.

    , , , , , et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013; 45: 1150–1159.

  28. 28.

    , , , . Genetic and environmental influences on alcohol, caffeine, cannabis, and nicotine use from early adolescence to middle adulthood. Arch Gen Psychiatry 2008; 65: 674–682.

  29. 29.

    , . The genetic epidemiology of cannabis use, abuse and dependence. Addiction 2006; 101: 801–812.

  30. 30.

    , , , , , et al. Genetic and environmental influences on cannabis use initiation and problematic use: a meta-analysis of twin studies. Addiction 2010; 105: 417–430.

  31. 31.

    , , , , , et al. The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation. Addict Biol 2013; 18: 846–850.

  32. 32.

    , , , , , et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009; 460: 748–752.

  33. 33.

    , , . Transitions in drinking in adolescent females: evidence from the Missouri adolescent female twin study. Alcohol Clin Exp Res 2000; 24: 914–923.

  34. 34.

    , , , , , et al. Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors. Psychol Med 2004; 34: 1519–1530.

  35. 35.

    , , , , , et al. A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. Biol Psychiatry 2011; 70: 513–518.

  36. 36.

    , , , , , et al. Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am J Hum Genet 2009; 85: 750–755.

  37. 37.

    , , , , , et al. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–575.

  38. 38.

    StataCorp. Stata Statistical Software: Release 12. StataCorp LP: College Station, TX, USA, 2011.

  39. 39.

    , , , , , et al. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013; 381: 1371–1379.

  40. 40.

    , , , . Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalization. Am J Psychiatry 2010; 167: 987–993.

  41. 41.

    , , , , , et al. Estimating the heritability of reporting stressful life events captured by common genetic variants. Psychol Med 2012; 43: 1965–1971.

  42. 42.

    , , , . Choice of residential location: chance, family influences, or genes? Twin Res Hum Genet 2005; 8: 22–26.

  43. 43.

    , , , , . Individual differences in adolescent religiosity in Finland: familial effects are modified by sex and region of residence. Twin Res 1999; 2: 108–114.

  44. 44.

    , , , , , et al. If cannabis caused schizophrenia—how many cannabis users may need to be prevented in order to prevent one case of schizophrenia? England and Wales calculations. Addiction 2009; 104: 1856–1861.

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Acknowledgements

Robert Power was funded by the Medical Research Council and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. This work was supported by National Institutes of Health Grants AA07535, AA0758O, AA07728, AA10249, AA13320, AA13321, AA14041, AA11998, AA17688, DA012854, DA018267, DA018660, DA23668 and DA019951; by Grants from the Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498, 6136022, 628911 and 1047956); by Grants from the Australian Research Council (A7960034, A79906588, A79801419, DP0770096, DP0212016 and DP0343921); and by the 5th Framework Programme (FP-5) GenomEUtwin Project (QLG2-CT-2002-01254). This research was further supported by the Centre for Research Excellence on Suicide Prevention (CRESP—Australia). KJHV is supported by the Netherlands Organization for Health Research and Development, ZonMW 31160212. We thank Richard Parker, Soad Hancock, Judith Moir, Sally Rodda, Pieta-Maree Shertock, Heather Park, Jill Wood, Pam Barton, Fran Husband, Adele Somerville, Ann Eldridge, Marlene Grace, Kerrie McAloney, Lisa Bowdler, Alexandre Todorov, Steven Crooks, David Smyth, Harry Beeby and Daniel Park. Finally, we thank the twins and their families for their participation.

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Affiliations

  1. MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London, London, UK

    • R A Power
    •  & M Zuhair
  2. Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia

    • R A Power
    •  & N R Wray
  3. Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University, Amsterdam, The Netherlands

    • K J H Verweij
  4. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    • G W Montgomery
    • , A K Henders
    • , S E Medland
    •  & N G Martin
  5. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    • A C Heath
    •  & P A F Madden

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The authors declare no conflict of interest.

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Correspondence to R A Power.

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DOI

https://doi.org/10.1038/mp.2014.51