Cigarette Smoking Behavior a Gateway to Opium Use Disorder: A Mendelian Randomization Analysis

Abdolhalim Rajabi, Azadeh Shojaei* (Corresponding Author), Leila Janani, Mojtaba Farjam, Hamid Reza Baradaran, Pedram Khosravi, Seyed Abbas Motevalian* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Gateway hypothesis presumes that using a psychotropic drug can increase the probability of using another drug. The study was to assess whether cigarette smoking is a gateway drug for subsequent opium use. Mendelian randomization (MR) analysis was applied to test and estimate the size of causal effect of cigarette smoking on opium use. The CHRNA3 rs1051730 polymorphism was used as an instrumental variable. A population-based case control study in the setting of Fasa Cohort Study was carried out using 477 cases and 531 controls based on their opium use status at the baseline of cohort study. The logistic two stage estimator method was applied. The Number of cigarettes smoked per day was associated with opium use (OR 1.17, 95% CI 1.15-1.19). In the MR analysis, rs1051730 T alleles were associated with increased risk of opium use among ever smokers (OR 5.73, 95% CI 1.72-19.07) however there found no evidence of association among never smokers. In instrumental variable analysis, showed that on average smoking every 1 more cigarette per day increases the odds of opium use by 1.17 (OR 1.17, 95%CI:1.14-1.19). The MR analysis found a positive finding on the relationship between cigarette smoking and opium use which supports the gateway hypothesis. It adds new information to the gateway theory regarding the relation of cigarette smoking and drug use, and increases our understanding of the importance of tobacco control for prevention of opium addiction.

Original languageEnglish
Pages (from-to)385-393
Number of pages9
JournalBehavior Genetics
Early online date12 Mar 2021
Publication statusPublished - Jul 2021

Bibliographical note

Funding: This study was funded by Iran University of Medical Sciences (Grant No. 9221128205).


  • Cigarette Smoking
  • Mendelian Randomization Analysis
  • Opium Dependence


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