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|Title:||The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes||Authors:||Cheong, Clara Y.
Holbrook, Joanna D.
Godfrey, Keith M.
Teh, Ai Ling
MacIsaac, Julia L.
Mah, Sarah M.
Chong, Mary F. F.
Meaney, Michael J.
Buschdorf, Jan Paul
Kobor, Michael S.
McEwen, Lisa M.
Gluckman, Peter D.
|Keywords:||DRNTU::Science::Biological sciences::Microbiology||Issue Date:||2014||Source:||Teh, A. L., Pan, H., Chen, L., Ong, M. L., Dogra, S., Wong, J., et al. (2014). The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes. Genome Research, 24(7), 1064-1074.||Series/Report no.:||Genome research||Abstract:||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.||URI:||https://hdl.handle.net/10356/104872
|ISSN:||1088-9051||DOI:||10.1101/gr.171439.113||Rights:||© 2014 The Authors. This paper was published in Genome Research and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1101/gr.171439.113]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SCSE Journal Articles|
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