Digital methylation assessments of alcohol and cigarette consumption account for common variance in accelerated epigenetic ageing.

Smoking and Heavy Alcohol Consumption (HAC) are established risk factors for myriad complex disorders of ageing. Yet many prior studies of Epigenetic Ageing (EA) have shown only modest effects of smoking and drinking on accelerated ageing. One potential reason for this conundrum might be the reliance of some prior EA studies on self-reported substance use, which may be unreliable in many samples. To test whether novel, non-self-reported indices would show a stronger association of smoking and HAC to EA, we used methylation sensitive digital PCR (MSdPCR) and data from 437 African American subjects from Wave 7 of the Family and Community Health Study Offspring Cohort to examine the effects of subjective and objective measures of smoking and HAC on 7 indices of EA. Because of limited overall correlations between the various EA indices, we examined patterns of association separately for each index. Consistent with expectations, MSdPCR assessments of smoking and HAC, but not self-reported alcohol consumption, were strongly correlated with accelerated EA. MSdPCR assessments of smoking and HAC accounted for 57% of GrimAge acceleration and the shared variance in GrimAge and DunedinPOAM accelerated EA. We conclude that MSdPCR assessments of smoking and HAC are valuable tools for understanding EA, represent directly targetable conditions for the prevention of premature ageing, and substantially improve upon self-reported assessment of smoking and HAC.