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Genetically contextual effects of smoking on genome wide DNA methylation
Journal article   Peer reviewed

Genetically contextual effects of smoking on genome wide DNA methylation

Meeshanthini V Dogan, Steven R H Beach and Robert A Philibert
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.174(6), pp.595-607
09/2017
DOI: 10.1002/ajmg.b.32565
PMCID: PMC5561723
PMID: 28686328
url
https://www.ncbi.nlm.nih.gov/pmc/articles/5561723View
Open Access

Abstract

Smoking is the leading cause of death in the United States. It exerts its effects by increasing susceptibility to a variety of complex disorders among those who smoke, and if pregnant, to their unborn children. In prior efforts to understand the epigenetic mechanisms through which this increased vulnerability is conveyed, a number of investigators have conducted genome wide methylation analyses. Unfortunately, secondary to methodological limitations, these studies were unable to examine methylation in gene regions with significant amounts of genetic variation. Using genome wide genetic and epigenetic data from the Framingham Heart Study, we re-examined the relationship of smoking status to genome wide methylation status. When only methylation status is considered, smoking was significantly associated with differential methylation in 310 genes that map to a variety of biological process and cellular differentiation pathways. However, when SNP effects on the magnitude of smoking associated methylation changes are also considered, cis and trans-interaction effects were noted at a total of 266 and 4353 genes with no marked enrichment for any biological pathways. Furthermore, the SNP variation participating in the significant interaction effects is enriched for loci previously associated with complex medical illnesses. The enlarged scope of the methylome shown to be affected by smoking may better explicate the mediational pathways linking smoking with a myriad of smoking related complex syndromes. Additionally, these results strongly suggest that combined epigenetic and genetic data analyses may be critical for a more complete understanding of the relationship between environmental variables, such as smoking, and pathophysiological outcomes.
 Genetic Markers DNA Methylation Genome-Wide Association Study Epigenesis, Genetic Humans Female Male Smoking - genetics Genome, Human Longitudinal Studies

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