Title |
The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes
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Published in |
Genome Research, April 2014
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DOI | 10.1101/gr.171439.113 |
Pubmed ID | |
Authors |
Ai Ling Teh, Hong Pan, Li Chen, Mei-Lyn Ong, Shaillay Dogra, Johnny Wong, Julia L. MacIsaac, Sarah M. Mah, Lisa M. McEwen, Seang-Mei Saw, Keith M. Godfrey, Yap-Seng Chong, Kenneth Kwek, Chee-Keong Kwoh, Shu-E. Soh, Mary F.F. Chong, Sheila Barton, Neerja Karnani, Clara Y. Cheong, Jan Paul Buschdorf, Walter Stünkel, Michael S. Kobor, Michael J. Meaney, Peter D. Gluckman, Joanna D. Holbrook |
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. |
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United States | 5 | 28% |
Canada | 4 | 22% |
Switzerland | 1 | 6% |
Argentina | 1 | 6% |
United Arab Emirates | 1 | 6% |
United Kingdom | 1 | 6% |
Unknown | 5 | 28% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 10 | 56% |
Scientists | 5 | 28% |
Science communicators (journalists, bloggers, editors) | 2 | 11% |
Practitioners (doctors, other healthcare professionals) | 1 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 4 | 1% |
Canada | 3 | <1% |
United States | 2 | <1% |
Hong Kong | 1 | <1% |
Germany | 1 | <1% |
Spain | 1 | <1% |
Switzerland | 1 | <1% |
Unknown | 332 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 76 | 22% |
Researcher | 70 | 20% |
Student > Bachelor | 41 | 12% |
Student > Master | 33 | 10% |
Student > Doctoral Student | 23 | 7% |
Other | 58 | 17% |
Unknown | 44 | 13% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 84 | 24% |
Biochemistry, Genetics and Molecular Biology | 55 | 16% |
Medicine and Dentistry | 53 | 15% |
Psychology | 19 | 6% |
Neuroscience | 16 | 5% |
Other | 54 | 16% |
Unknown | 64 | 19% |