B1287 - Impact of NCAM1-TTC12-ANKK1-DRD2 gene cluster on smoking behaviour impulsivity and reward in adolescence - 04/01/2012
The aims of this project are to conduct genomewide DNA methylation analyses of peripheral blood leukocytes (PBL) in two groups of children; those born late preterm and those born at term with low birthweight who are participants of the ALSPAC. The associations of genomewide and gene specific methylation patterns at birth (cord blood) with lung function outcomes at 8 years and 15-17 years will be investigated initially. For differentially methylated regions (DMRs) identified in this discovery phase, methylation analyses will be repeated at 7 years and 15-17 years in the same subjects to examine longitudinal changes. Additionally, associations of prenatal exposure to tobacco smoke and maternal nutrition with methylation of cord blood DNA will be examined. Specific hypotheses to be tested in this project are: 1.Differences in genome-wide and gene-specific DNA methylation are observed when comparing cord PBL from preterm infants and term infants with evidence of intrauterine growth restriction compared with term, appropriately grown infants and these DMRs are associated with abnormal lung function in later childhood. 2.DMRs identified at birth in association with abnormalities of long-term lung function are modified by postnatal exposures including growth rate, diet and environmental tobacco smoke, and these modifications are associated with different lung function trajectories. 3. Maternal smoking and nutrition during pregnancy; total energy and protein intake and estimated micronutrient intake of substances involved in 1-carbon metabolism, are associated with DNA methylation of genes linked with abnormal long term lung function.