The causal effect of cigarette smoking on healthcare costs

Knowledge of the impact of smoking on healthcare costs is important for establishing the external effects of smoking and for evaluating policies intended to modify this behavior. Conventional analysis of this association is difficult because of omitted variable bias, reverse causality, and measurement error. We approached these challenges using a Mendelian Randomization study design, in which genetic variants associated with smoking behaviors were used as instrumental variables. We undertook genome wide association studies to identify genetic variants associated with smoking initiation and a composite index of lifetime smoking on up to 300,045 individuals in the UK Biobank cohort. These variants were used in two-stage least square models and a variety of sensitivity analyses. All results were concordant in indicating a substantial impact of each smoking exposure on annual inpatient hospital costs Our results indicate a substantial impact of smoking on hospital costs. Genetic liability to initiate smoking – ever versus never having smoked – was estimated to increase mean per-patient annual hospital costs by £477 (95% confidence interval (CI): £187 to £766). A one unit change in genetic liability a composite index reflecting the cumulative health impacts of smoking was estimated to increase these costs by £204 (95% CI: £105 to £303). Models conditioning on the causal effect of risk tolerance were not robust to weak instruments for this exposure. Our findings have implications for the scale of external effects that smokers impose on others, and on the probable cost-effectiveness of smoking interventions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PD, HMS, GDS, MM and LDH are members of the MRC Integrative Epidemiology Unit at the University of Bristol which is supported by the Medical Research Council and the University of Bristol (MC\_UU\_00011/1, MC\_UU\_00011/7). PD acknowledges support from a Medical Research Council Skills Development Fellowship (MR/P014259/1). HMS is supported by the European Research Council (Reference: 758813 MHINT). LDH was supported by Health Foundation grant: Social and economic consequences of health status - Causal inference methods and longitudinal, intergenerational data. This was awarded under the Social and Economic Value of Health programme (Award reference 807293) and a Career Development Award from the UK Medical Research Council (MR/M020894/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Analysis code is available at www.github.com/pdixon-econ/MR\_smoking\_costs. Data is available on application to UK Biobank