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Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design

Published online by Cambridge University Press:  13 March 2018

Lindsey A. Hines*
Affiliation:
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England Centre for Adolescent Health, Royal Children's Hospital, Murdoch Children Research Institute, Parkville, Victoria, Australia
Katherine I. Morley
Affiliation:
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Australia
Fruhling Rijsdijk
Affiliation:
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England
John Strang
Affiliation:
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England
Arpana Agrawal
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
Elliot C. Nelson
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
Dixie Statham
Affiliation:
School of Social Sciences, University of the Sunshine Coast, Queensland, Australia
Nicholas G. Martin
Affiliation:
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Michael T. Lynskey
Affiliation:
Addictions Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England
*
Author for correspondence: Lindsey A Hines, E-mail: lindsey.a.hines@kcl.ac.uk

Abstract

Background

The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.

Methods

A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.

Results

Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.

Conclusions

There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

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