title: Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans.
abstract: Cigarette smoking is an environmental risk factor for many chronic diseases, and disease risk can often be managed by smoking control. Smoking can induce cellular and molecular changes, including epigenetic modification, but the short- and long-term epigenetic modifications caused by cigarette smoking at the gene level have not been well understood. Recent studies have identified smoking-related DNA methylation (DNAm) sites in Caucasians. To determine whether the same DNAm sites associate with smoking in African Americans, and to identify novel smoking-related DNAm sites, we conducted a methylome-wide association study of cigarette smoking using a discovery sample of 972 African Americans, and a replication sample of 239 African Americans with two array-based methods. Among 15 DNAm sites significantly associated with smoking after correction for multiple testing in our discovery sample, 5 DNAm sites are replicated in an independent cohort, and 14 sites in the replication sample have effects in the same direction as in the discovery sample. The top two smoking-related DNAm sites in F2RL3 (factor II receptor-like 3) and GPR15 (G-protein-coupled receptor 15) observed in African Americans are consistent with previous findings in Caucasians. The associations between the replicated DNAm sites and smoking remain significant after adjusting for genetic background. Despite the distinct genetic background between African Americans and Caucasians, the DNAm from the two ethnic groups shares common associations with cigarette smoking, which suggests a common molecular mechanism of epigenetic modification influenced by environmental exposure.
authors: Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road NE #3049, Atlanta, GA, 30322, USA. yvsun@emory.edu
authors: Yan V
authors: YV
authors: Sun
authors: Alicia K
authors: AK
authors: Smith
authors: Karen N
authors: KN
authors: Conneely
authors: Qiuzhi
authors: Q
authors: Chang
authors: Weiyan
authors: W
authors: Li
authors: Alicia
authors: A
authors: Lazarus
authors: Jennifer A
authors: JA
authors: Smith
authors: Lynn M
authors: LM
authors: Almli
authors: Elisabeth B
authors: EB
authors: Binder
authors: Torsten
authors: T
authors: Klengel
authors: Dorthie
authors: D
authors: Cross
authors: Stephen T
authors: ST
authors: Turner
authors: Kerry J
authors: KJ
authors: Ressler
authors: Sharon L R
authors: SL
authors: Kardia
mesh_terms: D001741:Black or African American / Q000235:genetics*; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D025341:Principal Component Analysis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D018179:Receptors, Thrombin / Q000235:genetics; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D011795:Surveys and Questionnaires
chemical_list: C103539:GPR15 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D018179:Receptors, Thrombin; C112908:protease-activated receptor 4
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