The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2014
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| Online Access: | https://hdl.handle.net/10356/104872 http://hdl.handle.net/10220/20310 |
| _version_ | 1811693311645188096 |
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| author | Cheong, Clara Y. Holbrook, Joanna D. Barton, Sheila Karnani, Neerja Godfrey, Keith M. Teh, Ai Ling MacIsaac, Julia L. Mah, Sarah M. Chong, Yap-Seng Kwoh, Chee-Keong Stünkel, Walter Chen, Li Kwek, Kenneth Soh, Shu-E. Chong, Mary F. F. Meaney, Michael J. Ong, Mei-Lyn Wong, Johnny Buschdorf, Jan Paul Kobor, Michael S. Pan, Hong Dogra, Shaillay McEwen, Lisa M. Saw, Seang-Mei Gluckman, Peter D. |
| author2 | School of Computer Engineering |
| author_facet | School of Computer Engineering Cheong, Clara Y. Holbrook, Joanna D. Barton, Sheila Karnani, Neerja Godfrey, Keith M. Teh, Ai Ling MacIsaac, Julia L. Mah, Sarah M. Chong, Yap-Seng Kwoh, Chee-Keong Stünkel, Walter Chen, Li Kwek, Kenneth Soh, Shu-E. Chong, Mary F. F. Meaney, Michael J. Ong, Mei-Lyn Wong, Johnny Buschdorf, Jan Paul Kobor, Michael S. Pan, Hong Dogra, Shaillay McEwen, Lisa M. Saw, Seang-Mei Gluckman, Peter D. |
| author_sort | Cheong, Clara Y. |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T06:49:40Z |
| format | Journal Article |
| id | ntu-10356/104872 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:49:40Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | ntu-10356/1048722022-02-16T16:30:44Z The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes Cheong, Clara Y. Holbrook, Joanna D. Barton, Sheila Karnani, Neerja Godfrey, Keith M. Teh, Ai Ling MacIsaac, Julia L. Mah, Sarah M. Chong, Yap-Seng Kwoh, Chee-Keong Stünkel, Walter Chen, Li Kwek, Kenneth Soh, Shu-E. Chong, Mary F. F. Meaney, Michael J. Ong, Mei-Lyn Wong, Johnny Buschdorf, Jan Paul Kobor, Michael S. Pan, Hong Dogra, Shaillay McEwen, Lisa M. Saw, Seang-Mei Gluckman, Peter D. School of Computer Engineering DRNTU::Science::Biological sciences::Microbiology 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. Published version 2014-08-18T01:12:24Z 2019-12-06T21:41:41Z 2014-08-18T01:12:24Z 2019-12-06T21:41:41Z 2014 2014 Journal Article 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. 1088-9051 https://hdl.handle.net/10356/104872 http://hdl.handle.net/10220/20310 10.1101/gr.171439.113 24709820 en Genome research © 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. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences::Microbiology Cheong, Clara Y. Holbrook, Joanna D. Barton, Sheila Karnani, Neerja Godfrey, Keith M. Teh, Ai Ling MacIsaac, Julia L. Mah, Sarah M. Chong, Yap-Seng Kwoh, Chee-Keong Stünkel, Walter Chen, Li Kwek, Kenneth Soh, Shu-E. Chong, Mary F. F. Meaney, Michael J. Ong, Mei-Lyn Wong, Johnny Buschdorf, Jan Paul Kobor, Michael S. Pan, Hong Dogra, Shaillay McEwen, Lisa M. Saw, Seang-Mei Gluckman, Peter D. The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title | The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title_full | The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title_fullStr | The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title_full_unstemmed | The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title_short | The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes |
| title_sort | effect of genotype and in utero environment on interindividual variation in neonate dna methylomes |
| topic | DRNTU::Science::Biological sciences::Microbiology |
| url | https://hdl.handle.net/10356/104872 http://hdl.handle.net/10220/20310 |
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