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Human Genetics

, Volume 132, Issue 9, pp 1027–1037 | Cite as

Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans

  • Yan V. SunEmail author
  • Alicia K. Smith
  • Karen N. Conneely
  • Qiuzhi Chang
  • Weiyan Li
  • Alicia Lazarus
  • Jennifer A. Smith
  • Lynn M. Almli
  • Elisabeth B. Binder
  • Torsten Klengel
  • Dorthie Cross
  • Stephen T. Turner
  • Kerry J. Ressler
  • Sharon L. R. Kardia
Original Investigation

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.

Keywords

Cigarette Smoking African American Current Smoking Status Replication Sample Discovery Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors gratefully acknowledge the participants of the study. Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, Grant numbers HL100185 and HL100245 from National Heart, Lung, Blood Institute. Grady Trauma Project (GTP) is supported, in part, by NIH/NIDA T32 DA15040, and support for AKS was provided by MH085806. The authors thank Richard Barfield and Varun Kilaru for technical assistance.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

439_2013_1311_MOESM1_ESM.xlsx (21 kb)
Supplementary Table 1: Significant smoking-related DNAm sites with FDR q value less than 0.05 (XLSX 21 kb)
439_2013_1311_MOESM2_ESM.xlsx (24 kb)
Supplementary Table 2: Replication of smoking-related DNAm on the level of genes using human methylation 450 k array. (XLSX 23 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Yan V. Sun
    • 1
    • 2
    Email author
  • Alicia K. Smith
    • 3
  • Karen N. Conneely
    • 4
  • Qiuzhi Chang
    • 1
  • Weiyan Li
    • 1
  • Alicia Lazarus
    • 5
  • Jennifer A. Smith
    • 5
  • Lynn M. Almli
    • 3
  • Elisabeth B. Binder
    • 3
    • 6
  • Torsten Klengel
    • 6
  • Dorthie Cross
    • 3
  • Stephen T. Turner
    • 7
  • Kerry J. Ressler
    • 3
  • Sharon L. R. Kardia
    • 5
  1. 1.Department of Epidemiology, Rollins School of Public HealthEmory UniversityAtlantaUSA
  2. 2.Department of Biomedical Informatics, School of MedicineEmory UniversityAtlantaUSA
  3. 3.Departments of Psychiatry and Behavioral Sciences, School of MedicineEmory UniversityAtlantaUSA
  4. 4.Department of Human Genetics, School of MedicineEmory UniversityAtlantaUSA
  5. 5.Department of Epidemiology, School of Public HealthUniversity of MichiganAnn ArborUSA
  6. 6.Max-Planck Institute of PsychiatryMunichGermany
  7. 7.Division of Nephrology and HypertensionMayo ClinicRochesterUSA

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