The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

TitleThe effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.
Publication TypeJournal Article
Year of Publication2014
AuthorsTeh ALing, Pan H, Chen L, Ong M-L, Dogra S, Wong J, MacIsaac JL, Mah SM, McEwen LM, Saw S-M, Godfrey KM, Chong Y-S, Kwek K, Kwoh C-K, Soh S-E, Chong MFF, Barton S, Karnani N, Cheong CY, Buschdorf JPaul, Stünkel W, Kobor MS, Meaney MJ, Gluckman PD, Holbrook JD
JournalGenome Res
Date Published2014 Jul
KeywordsComputational Biology, CpG Islands, DNA Methylation, Environment, Epigenesis, Genetic, Epigenomics, Female, Gene-Environment Interaction, Genetic Heterogeneity, Genotype, Humans, Infant, Newborn, Male, Polymorphism, Single Nucleotide, Pregnancy, Quantitative Trait Loci, Risk Factors, Transcriptome

Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained ∼25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.

Alternate JournalGenome Res.
PubMed ID24709820
PubMed Central IDPMC4079963
Grant ListMC_UP_A620_1017 / / Medical Research Council / United Kingdom