Blood- and brain-based genome-wide association studies of smoking
Abstract
Background: Self-reported smoking is often incorporated into disease prediction tools but suffers from recall bias and does not capture passive exposure. Blood-based DNA methylation (DNAm) is an objective way to assess smoking. However, studies have not fully explored tissue-specificity or epigenome-wide coverage beyond array data. Here, we update the existing biomarkers of smoking and conduct a detailed analysis of the associations between blood DNAm and self-reported smoking.
Methods and Findings: A blood-based Bayesian epigenome-wide association study (EWAS) of smoking was carried out in 17,865 Generation Scotland individuals at ~850k CpG sites (Illumina EPIC array). For 24 pairs of smokers and non-smokers a high-resolution approach was implemented (~4 million sites, TWIST methylome panel). A DNAm-derived biomarker of smoking (mCigarette) was tested in the independent Lothian Birth Cohort 1936 (n=882, Illumina 450k array) and in the ALSPAC parents and offspring at four time points (range n=496-1,207). To explore tissue specific signals, EWASs of smoking were run across five brain regions for 14 individuals using DNAm from the EPIC array. Lastly, genome-wide association studies (GWASs) of smoking pack years and an epigenetic score for smoking (GrimAge DNAm pack years) were conducted (n=17,105). The primary EWAS analyses identified two novel genome-wide significant loci, mapping to genes related to addiction and carcinogenesis. Associations with CpG sites which are…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 17,865 participants or records.
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