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Epigenome-wide analysis uncovers a blood-based DNA methylation biomarker of lifetime cannabis use
- Source :
- Am J Med Genet B Neuropsychiatr Genet
- Publication Year :
- 2020
-
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.
- Subjects :
- Oncology
Adult
Genetic Markers
medicine.medical_specialty
Substance-Related Disorders
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Article
Epigenesis, Genetic
Cellular and Molecular Neuroscience
Epigenome
Internal medicine
medicine
Humans
Prospective Studies
Prospective cohort study
Genetics (clinical)
Genetic association
Aged
Cannabis
biology
business.industry
Area under the curve
dNaM
DNA Methylation
Middle Aged
biology.organism_classification
Psychiatry and Mental health
Case-Control Studies
DNA methylation
Biomarker (medicine)
Female
business
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 1552485X
- Volume :
- 186
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- Accession number :
- edsair.doi.dedup.....e7b42c6eb0df9a23f149690f24d5d1e3