Early-life tobacco exposure and self-reported periodontal disease in adulthood: an observational and Mendelian randomization study

Periodontal disease (PD) is a common non-communicable disease, and smoking is a major modifiable risk factor. Despite abundant evidence on the smoking intensity and cessation, the association between early-life tobacco exposure and PD remains unclear. In this observational and Mendelian randomization (MR) study, we aimed to investigate the associations of early-life tobacco exposure, including prenatal tobacco exposure resulting from maternal smoking during pregnancy and participants’ early smoking initiation indicated by age of smoking initiation, with self-reported PD in adulthood. Potential biological pathways were also explored. Observational data were obtained from the UK Biobank. Logistic regression was used to estimate odds ratios. Two-sample MR analyses were performed using GWAS summary statistics. Mediation analyses were conducted using plasma proteomics data from the UK Biobank to explore potential biological pathways. Maternal smoking during pregnancy was associated with 13% higher odds of self-reported PD (95% confidence interval: 11% to 15%). Compared with never smokers, smoking initiation in childhood, adolescence, and adulthood was associated with 26% (21% to 31%), 13% (10% to 16%), and 7% (4% to 9%) higher odds, respectively, with a dose–response trend observed ( P < 0.001). MR analyses showed 2.9-fold (2.05 to 4.09) higher odds of PD for maternal smoking during pregnancy and a 34% (16% to 47%) lower odds for per standard-deviation increase in age of smoking initiation. Mediation analysis identified 16 and 183 plasma proteins as potential mediators on the associations of maternal smoking during pregnancy and smoking initiation with self-reported PD, mainly enriched in immune-related pathways. Maternal smoking during pregnancy and earlier smoking initiation were associated with higher odds of self-reported PD. Immune-related processes may be involved in these associations. These findings support the consideration of smoking-related prevention efforts for PD from the very early stages of life.