Epigenome‐wide analysis uncovers a blood‐based DNA methylation biomarker of lifetime cannabis use
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Abstract
Cannabis use is highly prevalent and is associated with adverse and beneficial effects. To better understand the full spectrum of health consequences, biomarkers that accurately classify cannabis use are needed. DNA methylation (DNAm) is an excellent candidate, yet no blood‐based epigenome‐wide association studies (EWAS) in humans exist. We conducted an EWAS of lifetime cannabis use (ever vs. never) using blood‐based DNAm data from a case–cohort study within Sister Study, a prospective cohort of women at risk of developing breast cancer (Discovery N = 1,730 [855 ever users]; Replication N = 853 [392 ever users]). We identified and replicated an association with lifetime cannabis use at cg15973234 (CEMIP): combined p = 3.3 × 10 −8 . We found no overlap between published blood‐based cis‐meQTLs of cg15973234 and reported lifetime cannabis use‐associated single nucleotide polymorphism (SNPs; p < .05), suggesting that the observed DNAm difference was driven by cannabis exposure. We also developed a multi‐CpG classifier of lifetime cannabis use using penalized regression of top EWAS CpGs. The resulting 50‐CpG classifier produced an area under the curve (AUC) = 0.74 (95% CI [0.72, 0.76], p = 2.00 × 10 −5 ) in the discovery sample and AUC = 0.54 ([0.51, 0.57], p = 2.87 × 10 −2 ) in the replication sample. Our EWAS findings provide evidence that blood‐based DNAm is associated with lifetime cannabis use.
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- Authors
- Markunas, C. A., Hancock, D. B., Xu, Z., Quach, B. C., Fang, F., Sandler, D. P., Johnson, E. O., & Taylor, J. A.
- Affiliations
- RTI International (US)
- National Institutes of Health (US)
- Corresponding author
- Taylor, Jack A.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2020-08-17
- Volume
- 186
- Issue
- 3
- Pages
- 173-182
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC8296847
- OpenAlex
- W3056482323
- Cited by
- 31
- References
- 52
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 1
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences (ZO1 ES‐044005, ZO1 ES‐049032, ZO1 ES‐049033)
- RTI International (Fellow Program)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- cannabis use, DNA methylation, blood-based biomarkers, epigenome-wide association study, CEMIP, methylation quantitative trait loci, Sister Study, breast cancer risk, women
- MeSH terms
- Epigenome, Adult, Aged, Cannabis, Female, Genetic Markers, Humans, Middle Aged, Prospective Studies, Case-Control Studies, DNA Methylation, Substance-Related Disorders, Polymorphism, Single Nucleotide, Epigenesis, Genetic, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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