Correlation of global and gene-specific DNA methylation in maternal-infant pairs.
The inheritance of DNA methylation patterns is a popular theory to explain the influence of parental genetic and environmental factors on the phenotype of their offspring but few studies have examined this relationship in humans. Using 120 paired maternal-umbilical cord blood samples randomly selected from a prospective birth cohort in Bangladesh, we quantified DNA methylation by pyrosequencing seven CpG positions in the promoter region of p16, four CpG positions in the promoter region of p53, LINE-1 and Alu. Positive correlations were observed between maternal and umbilical cord blood at p16, LINE-1, and Alu but not p53. Multiple linear regression models observed a significant association between maternal and umbilical cord blood at LINE-1 and Alu (LINE-1: β = 0.63, p<0.0001; Alu: β = 0.28, p = 0.009). After adjusting for multiple comparisons, maternal methylation of p16 at position 4 significantly predicted methylation at the same position in umbilical cord blood (β = 0.43, p = <0.0001). These models explained 48%, 5% and 16% of the observed variability in umbilical cord %5mC for LINE-1, Alu and p16 at position 4, respectively. These results suggest that DNA methylation in maternal blood was correlated with her offspring at LINE-1, Alu, and p16 but not p53. Additional studies are needed to confirm whether these observed associations were due to the inheritance of epigenetic events or the shared environment between mother and fetus. Future studies should also use a multi-generational family-based design that would quantify both maternal and paternal contributions to DNA methylation in offspring across more than one generation.
Environmental Health Department, Harvard School of Public Health, Boston, Massachusetts, United States of America. mkile@hsph.harvard.edu
Molly L
ML
Kile
Andrea
A
Baccarelli
Letizia
L
Tarantini
Elaine
E
Hoffman
Robert O
RO
Wright
David C
DC
Christiani
D001459:Bangladesh; D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D006801:Humans; D007223:Infant; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011446:Prospective Studies
D017931:DNA Primers