Bi-directional effects between loneliness, smoking and alcohol use: Evidence from a Mendelian randomisation study

Robyn E Wootton*, Marcus R Munafo, Jorien L Treur*, et al.

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

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Background and Aims:
Loneliness is associated with cigarette smoking and problematic alcohol use. Observational evidence suggests these associations arise because loneliness increases substance use; however, there is potential for reverse causation (problematic drinking damages social networks, leading to loneliness). With conventional epidemiological methods, controlling for (residual) confounding and reverse causality is difficult. This study applied Mendelian randomisation (MR) to assess bi-directional causal effects among loneliness, smoking behaviour and alcohol (mis)use. MR uses genetic variants as instrumental variables to estimate the causal effect of an exposure on an outcome, if the assumptions are satisfied

Our primary method was inverse-variance weighted regression and the robustness of these findings was assessed with five different sensitivity methods.

Setting: European ancestry.

Participants: Summary-level data were drawn from the largest available independent genome-wide association studies (GWAS) of loneliness (n=511,280), smoking (initiation (n=249,171), cigarettes-per-day (n=249,171) and cessation (n=143,852)), alcoholic drinks-per-week (n=226,223) and alcohol dependence (n=46,568).

Measurements: Genetic variants predictive of the exposure variable were selected as instruments from the respective GWAS.

Findings: There was weak evidence of increased loneliness leading to higher likelihood of initiating smoking and smoking more cigarettes, and a lower likelihood of quitting smoking. Additionally, there was evidence that initiating smoking increases loneliness (IVW β=0.30 (0.22-0.38), p=2.8x10-13). We found no clear evidence for a causal effect of loneliness on drinks per week (IVW β=0.01 (-0.11, 0.13), p=0.865) or alcohol dependence (IVW β=0.09 (-0.19, 0.36), p=0.533) nor of alcohol use on loneliness (drinks per week IVW β=0.09 (-0.02, 0.22), p=0.076; alcohol dependence IVW β=0.06 (-0.02, 0.13), p=0.162).

Conclusions: There appears to be tentative evidence for causal, bidirectional, increasing effects between loneliness and cigarette smoking, especially for smoking initiation increasing loneliness.
Original languageEnglish
Number of pages7
Publication statusPublished - 29 Jun 2020

Structured keywords

  • Physical and Mental Health
  • Tobacco and Alcohol


  • alcohol dependence
  • alcohol use
  • health behaviours
  • loneliness
  • Mendelian randomization
  • smoking behaviour
  • social isolation

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