The 2006 US Surgeon General’s report, based on a comprehensive review of the scientific literature, identified a number of health risks from second-hand smoke (SHS) exposure, including elevated risk of cardiovascular disease and lung cancer in those exposed (1). Furthermore, the report concluded that there is no risk-free level of SHS exposure and that a large proportion of the population is exposed to SHS in their homes and workplaces in spite of progress in tobacco control.

Despite this substantial body of research, the impact of SHS on health remains under dispute, with some large-scale studies not supporting a causal relationship between SHS exposure and tobacco-related mortality (2). One reason for this may be due to misclassification (3), for example where studies based on reports of smoking in a partner underestimate risks. Objective biomarkers, such as cotinine and DNA methylation, can increase the measurement precision of the underlying SHS exposure to reduce information bias due to misreporting, and may also serve as better indicators of later life disease (4).

One previous study conducted using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) showed low levels of cotinine in non-smoking women whose partners smoked (5), indicating a limited biological impact of SHS. However, the association between SHS exposure and DNA methylation, another objective measure which has been found to be a more accurate predictor of long term smoke exposure (6), has not been thoroughly evaluated. While associations between DNA methylation and passive smoke exposure have been identified in relation to intra-uterine exposure to maternal smoking (7, 8), there have been few studies investigating passive smoke exposure postnatally, and those that have been conducted have evaluated methylation at a limited number of cytosine-phosphate-guanine (CpG) sites (9, 10).

Within the Accessible Resource for Integrated Epigenomics Studies (ARIES) subset of ALSPAC, SHS has been assessed in terms of both prenatal and postnatal smoke exposure in the ALSPAC offspring (8). However, Prince et al [unpublished] found that evidence for differential methylation related to passive (parental) smoke exposure in the ALSPAC offspring is likely (residually) confounded by prenatal smoking by the ALSPAC mothers. This risk of confounding (and collinearity between the prenatal smoking and SHS measures) could be reduced by examining DNA methylation in relation to SHS exposure in the ALSPAC adults, assessed based on reported partner smoking status and SHS exposure at work and in the home.