Assessing the causal effects of environmental tobacco smoke exposure: a meta-analytic Mendelian randomization study

First-hand smoking is a major cause of global morbidity and mortality. Exposure to environmental tobacco smoke (ETS; "second-hand" or "passive smoking") may also cause ill health, but establishing ETS as the cause is challenging, in part due to confounding and reverse causation.

We applied Mendelian randomization (MR) to investigate the causal effects of ETS. We use four approaches to instrument ETS exposure: The first and second used an index individual's parent's genetically predicted smoking, independent of the index individual's genetically predicted smoking to assess the effects of that parent's smoking on the index individual. The third and fourth used one index individual's parent's genetically predicted smoking, independent of the other parent's genetically predicted smoking to assess the effects of the first parent's smoking on the second parent. We then meta-analyze the four MR approaches.

Our findings suggest a causal effect of genetically predicted ETS exposure on lung cancer and chronic obstructive pulmonary disease (PFDR < .001 for both). We did not find evidence supporting an effect on hypertension, depression, coronary heart disease, or stroke (PFDR = 1.000 for all four non-respiratory outcomes).

These results support existing public health measures to limit exposure to ETS.

We assess the causal effects of environmental tobacco smoking (ETS; "second-hand smoking" or "passive smoking") using a quasi-experimental method, Mendelian randomization, which is more robust to confounding than conventional epidemiological methods.To study the effects of ETS exposure, we used an index individual's parent's or spouses' genetically predicted smoking, independent of either the index's or the other parent's genetically predicted smoking when assessing the effect of that parent's smoking on the index individual or other parent, respectively. We then meta-analyze the effects of different relatives.This study extends the Mendelian randomization paradigm to assess ETS by examining the effect that one relative has on the other relative, independent of the other relative's smoking. In doing so, it adds a unique source of evidence that triangulates with prior research to indicate an effect of ETS exposure on lung cancer and chronic obstructive pulmonary disease.