B1280 - Smoking variable methylation at F2RL3 and intermediates of cardiovascular risk - 15/12/2011

B number: 
B1280
Principal applicant name: 
Dr Nic Timpson (University of Bristol, UK)
Co-applicants: 
Prof George Davey Smith (University of Bristol, UK)
Title of project: 
Smoking, variable methylation at F2RL3 and intermediates of cardiovascular risk.
Proposal summary: 

Aiming to use ALSPAC data and DNA samples as part of a wider project following up on the recent observations that smoking behaviour is associated with variable methylation at the coagulation factor II (thrombin) receptor-like locus (F2RL3) locus of chromosome 19. This work was the first to look at genomewide methylation data based on genomic DNA extracted from blood and as drawn by general practitioner for entry into the study. In a small number of samples (~180 in the discovery phase), individuals match nominally on age had self reported data on smoking available which allowed classification of smoking behaviour as never having smoked, former heavy smoker, or current heavy smoker; who never smoked tobacco products other than cigarettes; who reported no diagnosis of cancer. Within this sample, of around 60 current, heavy smokers, 60 former smokers and 60 never smokers, clear evidence for differential methylation of the F2RL3 was found (Figure 1 below), was the only signal coming from analysis of 27000 sites measured across the genome and was replicated in an independent analysis of a slightly larger (~100 in each smoking category) data set. Of note and pertinent to the nature or methylation as an environmentally modifiable feature, additional adjustment for age, alcohol consumption or BMI did not change the results substantially, methylation being consistently lower with smoking when comparing heavy smokers to never smokers.

Date proposal received: 
Thursday, 15 December, 2011
Date proposal approved: 
Thursday, 15 December, 2011
Keywords: 
Epigenetics , Smoking
Primary keyword: