Our efforts in GWAS focus on the EVE and TAGC consortia to provide greater samples size. We are also participating in the ABRIDGE consortium for integrative genomic analyses. Increasing evidence suggest the importance of pregnancy and early life factors in the etiology of asthma and allergy in childhood. Various investigators in the Epidemiology Branch have established a collaboration with the Norwegian Mother and Child Cohort (called MoBa), a population based cohort of approximately 100,000 pregnant women in Norway who are being followed until their children reach adulthood. I have established a collaboration with the asthma group in Norway around gene-environment interaction and epigenetics. I have been working on analyses of early childhood outcomes with the MoBa investigators and pre and postdoctoral trainees from NIEHS and Norway. Our finding (Haberg et al., 2009 and Haberg et al. 2010) that children of mothers with higher levels of folate had slightly higher risk of asthma phenotypes in early childhood is of potential public health importance. Our was the first human study to address a recent finding in mouse models that supplementation with folate and other methyl donors in pregnancy lead to an allergic asthma phenotype in offspring due to epigenetic mechanisms. Norway is an ideal place to examine this association because food is not fortified with folate. We are following the children to age seven to see whether this association is present with the more relevant phenotype of asthma at school age. We realize that many children have wheezing illness in the first few years of life and that much of this resolves by school age and does not become asthma. Therefore we have organized a follow-up of the MoBa cohort at age seven years when asthma is more reliably diagnosed and inhalant allergies have become common. Follow-up at age seven will enable high quality, well powered studies of genetics and epigenetics of childhood asthma and allergies, including consideration of interactions with environmental factors, including diet, parental smoking, wood burning and ambient air pollution. A major focus of this project is to examine effects of in utero exposures on the epigenome of newborns. For this purposes we measured DNA methylation in cord blood on approximately 1700 newborns from the Norwegian Mother and Child pregnancy cohort. We used the Illumina450K methylation bead chip. In the first paper to examine the effects of any in utero exposure using this platform we identified and replicated associations of maternal smoking with DNA methylation in a number of genes. We then followed up with a paper on the effects of timing of exposure. We created an international consortium of studies with DNA methylation measured with the Illumina450K in newbornsto collaborate on a meta-analysis of effects of maternal smoking on offspring methylation. The consortium plans to continue working together to examine a wide range of other exposures and outcomes. We have projects underway on maternal BMI, child BMI, birthweight, asthma, atopy, pulmonary function, maternal alcohol intake.
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