DNA methylation analyses in infants reveal signals correlated with fetal alcohol syndrome, maternal smoking, gender, and ethnicity

Alcohol exposure is known to impact several components of the one-carbon metabolism pathway, which is vital for providing methyl groups for DNA and peptide synthesis and for methylation modification of nucleotides and proteins. Methylation patterning in DNA is known to be altered across generations in specific situations in humans, including nutrient deprivation and smoking during pregnancy. We were interested in seeing whether heavy alcohol exposure during pregnancy, which is associated with fetal alcohol syndrome, influences genome-wide infant methylation patterning. From Guthrie card spots across over 100 infants of various genders, ethnicities, and maternal smoking and drinking status, we find two loci that are have significantly different methylation patterning associated with maternal drinking; cgXXX and cgYYY, the former near MCOLN3 and the latter in intergenic space. We also use available epidemiological information associated with our data set to replicate maternal smoking with infant methylation changes as well as replicate and expand upon methylation differences between genders and ethnicities. Case Control design with 72 cases and 73 controls. Our study sample of Guthrie card DNA from NY state infants contains 150 unique samples. Four samples were removed due to poor performance in the PCA analysis and another was removed because there is a set of identical twins in the study. As we were interested in studying the role ethnicity plays in methylation differences, we removed eight of the Hispanic and other ethnicity samples, leaving a total of 137 samples. The populations of the FAS cases and controls are matched for gender and ethnicity