Genetic and Smoking-Related Associations with DNA Methylation in Current and Former Smokers from the COPDGene Study

• Activity Number: 603
• Type: Contributed
• Date/Time: Thursday, August 7, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biometrics Section
• Author(s): Weiliang Qiu*+ and Michael H. Cho and Emily Wan and Jarrett Morrow and James Crapo and Edwin K. Silverman and Dawn L. DeMeo
• Companies: Brigham & Women's Hospital/Harvard and Harvard Medical School and Harvard Medical School and Brigham & Women's Hospital/Harvard Medical School and National Jewish Health and Harvard Medical School and Harvard Medical School
• Keywords: COPD ; DNA methylation ; smoking ; SNP ; COPDgene

Abstract

Cigarette smoking contributes to the leading causes of morbidity and mortality in the Western world-however the variable susceptibility to the health effects of cigarette smoking are incompletely understood. DNA methylation can be affected by both environmental factors and genetic sequence variation. We aim to assess if cigarette smoking and genetic variation are associated with overlapping or distinct sets of DNA methylation marks and pathways. We selected 85 Caucasian current and former smokers with available DNA and genome-wide genotyping from the COPDGene study and measured DNA methylation levels for 27,578 CpG sites. We detected 770 CpG sites significant only in the cis-methyQTL analysis and 1,287 CpG sites significant only in the smoking-CpG-association analysis. Only 43 CpG sites were significantly associated with both SNP variation and current smoking. Our results suggest that cigarette smoking and genetic factors (such as commons SNP variation) associate with the methylation levels of different sets of DNA methylation marks, the elucidation of which may partially explain the variable susceptibility to the health effects of cigarette smoking.