title: Coffee consumption is associated with DNA methylation levels of human blood.
abstract: Beneficial health effects have been attributed to coffee consumption, but it is not yet known whether epigenetics may have a role in this process. Here we associate epigenome-wide DNA methylation levels to habitual coffee consumption from two studies with blood (2100 and 215 participants), and one with saliva samples (256 participants). Adjusting for age, gender, and blood cell composition, one CpG (cg21566642 near ALPPL2) surpassed genome-wide significance (P=3.7 × 10-10) and from among 10 additional CpGs significant at P≤5.0 × 10-6, six were located within 1500 bps of a transcriptional start site. Results for these 11 top-ranked CpGs remained significant after further adjusting for smoking. Also, methylation levels of another 135 CpGs were influenced by both coffee drinking and smoking (P≤1.0 × 10-7). Functional enrichment analysis suggested that coffee-associated CpGs were located near transcription factor binding (P=1.2 × 10-6) and protein kinase activity genes (P=2.9 × 10-5). Interestingly, when we stratified by menopausal hormone therapy (MHT), methylation differences with coffee consumption were observed only in women who never used MHT. We did not replicate any of the associations found in blood in our saliva samples, suggesting that coffee may affect DNA methylation levels in immune cells of the blood but not in saliva.
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Chuang
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Austin
authors.initials: A
authors.lastname: Quach
authors.affiliation: HudsonAlpha Institute of Biotechnology, Huntsville, AL, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Absher
authors.affiliation: School of Medicine (Cardiovascular Medicine), Stanford University, Palo Alto, CA, USA.
authors.forename: Themistocles
authors.initials: T
authors.lastname: Assimes
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.|Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.affiliation: Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
authors.forename: Beate
authors.initials: B
authors.lastname: Ritz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003069:Coffee / Q000009:adverse effects*; D018899:CpG Islands; D004247:DNA / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012907:Smoking / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D003069:Coffee; D014157:Transcription Factors; D004247:DNA