RT Journal
A1 Teh, Ai Ling
A1 Pan, Hong
A1 Chen, Li
A1 Ong, Mei-Lyn
A1 Dogra, Shaillay
A1 Wong, Johnny
A1 MacIsaac, Julia L
A1 Mah, Sarah M
A1 McEwen, Lisa M
A1 Saw, Seang-Mei
A1 Godfrey, Keith M
A1 Chong, Yap-Seng
A1 Kwek, Kenneth
A1 Kwoh, Chee-Keong
A1 Soh, Shu-E
A1 Chong, Mary FF
A1 Barton, Sheila
A1 Karnani, Neerja
A1 Cheong, Clara Y
A1 Buschdorf, Jan Paul
A1 Stunkel, Walter
A1 Kobor, Michael S
A1 Meaney, Michael J
A1 Gluckman, Peter D
A1 Holbrook, Joanna D
T1 The effect of genotype and in utero environment on inter-individual variation in neonate DNA methylomes
JF Genome Research 
JO Genome Research 
YR 2014 
FD April 07 
DO 10.1101/gr.171439.113 
SP gr.171439.113 
UL http://genome.cshlp.org/content/early/2014/04/07/gr.171439.113.abstract 
AB 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 enduring effects of the prenatal environment.  Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, inter-individual 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 about 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.