Epigenetic signatures of smoking associate with cognitive function, brain structure, and mental and physical health outcomes in the Lothian Birth Cohort 1936.
Level 3 - non-randomized controlled study
Cohort study evaluating cross-sectional health associations at age 70 and MRI follow-up at age 73.
PubMed 31591380 · doi:10.1038/s41398-019-0576-5
What was done
Blood DNA methylation was profiled using the Illumina 450K assay in 895 adults aged 70 years from the Lothian Birth Cohort 1936 (LBC1936). A 230-CpG DNA methylation score was computed as an epigenetic proxy for smoking exposure. General linear models (ANCOVA) and logistic regression were used to examine associations of self-reported smoking and the methylation score with cognitive, physical, and psychosocial outcomes at age 70, as well as brain MRI volumetric measures at age 73 in a subset (n = 532).
What was found
The smoking DNA methylation score correlated with self-reported smoking status (P < 0.001, η² = 0.63) and pack years (r = 0.69, P < 0.001). Compared to self-reported smoking, the methylation marker showed stronger associations across outcomes, including visuospatial ability (P < 0.001, ηp² = 0.022), processing speed (P < 0.001, ηp² = 0.030), inflammatory markers (all P < 0.001, ηp² = 0.021 to 0.030), healthy diet (P < 0.001, ηp² = 0.052), traditional diet (P < 0.001, ηp² = 0.032), stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96), mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and age 73 MRI volumetric measures (all P < 0.001, ηp² = 0.030 to 0.052).
Why it matters
Epigenetic markers of smoking capture biologically relevant exposure beyond self-report and account for additional variance in late-life brain structure, cognitive performance, and mortality risk.
Limits
The sample is restricted to a racially and geographically homogeneous Scottish birth cohort at age 70–73, which may not generalize to younger or more diverse populations. MRI analysis was limited to an attrition-selected subset (n = 532), and the observational design cannot establish whether methylation changes causally mediate these health outcomes.
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