Assessing the Causal Effects of Environmental Tobacco Smoke Exposure: A meta-analytic Mendelian randomisation study

Smoking is a major cause of global morbidity and premature mortality. Exposure to environmental tobacco smoke (ETS; “second-hand” or “passive smoking”) may also contribute to ill health. However, it is difficult to establish causality given problems of confounding and reverse causation. We applied Mendelian randomisation to investigate evidence for causal effects. To instrument ETS exposure we used an index individual’s parent’s or spouse’s genetic liability to smoke, conditional on the index individual’s genetic liability. We then meta-analyse four MR approaches using this. Our findings suggest a causal effect of genetically predicted ETS exposure on lung cancer and chronic obstructive pulmonary disease (p _FDR < 0.001 for both). We did not find evidence supporting an effect on hypertension, depression, coronary heart disease, or stroke (p _FDR = 1.000 for all four non-respiratory outcomes); but this might reflect low statistical power. Overall, these results support public health measures to limit exposure to ETS.