Rauschert, S and Melton, PE and Heiskala, A and Karhunen, V and Burdge, G and Craig, JM and Godfrey, KM and Lillycrop, K and Mori, TA and Beilin, LJ and Oddy, WH and Pennell, C and Jarvelin, M-R and Sebert, S and Huang, R-C, Machine learning-based DNA methylation score for fetal exposure to maternal smoking: development and validation in samples collected from adolescents and adults, Environmental Health Perspectives, 128, (9) Article 97003. ISSN 0091-6765 (2020) [Refereed Article]
Copyright 2020 the authors
Methods: We used machine learning methods to create a score reflecting exposure to maternal smoking during pregnancy. This score is based on peripheral blood measurements of DNA methylation (Illumina's Infinium HumanMethylation450K BeadChip). The score was developed and tested in the Raine Study with data from 995 white 17-y-old participants using 10-fold cross-validation. The score was further tested and validated in independent data from the Northern Finland Birth Cohort 1986 (NFBC1986) (16-y-olds) and 1966 (NFBC1966) (31-y-olds). Further, three previously proposed DNA methylation scores were applied for comparison. The final score was developed with 204 CpGs using elastic net regression.
Results: Sensitivity and specificity values for the best performing previously developed classifier ("Reese Score") were 88% and 72% for Raine, 87% and 61% for NFBC1986 and 72% and 70% for NFBC1966, respectively; corresponding figures using the elastic net regression approach were 91% and 76% (Raine), 87% and 75% (NFBC1986), and 72% and 78% for NFBC1966.
Conclusion: We have developed a DNA methylation score for exposure to maternal smoking during pregnancy, outperforming the three previously developed scores. One possible application of the current score could be for model adjustment purposes or to assess its association with distal health outcomes where part of the effect can be attributed to maternal smoking. Further, it may provide a biomarker for fetal exposure to maternal smoking.
|Item Type:||Refereed Article|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Reproductive medicine|
|Research Field:||Foetal development and medicine|
|Objective Group:||Public health (excl. specific population health)|
|Objective Field:||Public health (excl. specific population health) not elsewhere classified|
|UTAS Author:||Melton, PE (Dr Phillip Melton)|
|UTAS Author:||Oddy, WH (Professor Wendy Oddy)|
|Web of Science® Times Cited:||1|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||4 View Download Statistics|
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