Genetic And Environmental Factors In Childhood Respiratory and Allergic Illness

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

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 are also using genome wide methylation techniques (Illumina Methyl450K) to examine whether levels of folate and other methyl donors in maternal blood are related to epigenetic changes in the offspring cord blood. We published the first paper to examine the effects of any in utero exposure using this platform. We identified and replicated a number of genes influenced by this exposure. We have followed this up by looking the critical timing for this exposure. We also have expanded our sample size to include about another 700 subjects. We are also trying to organize all other studies with Illumina Methyl450K data on newborns or young children to collaborate on a meta-analysis of effects of maternal smoking on offspring methylation. The meta-analysis approach has been very powerful in GWAS. 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 it is important to follow-up our findings by following the children to age seven year 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.