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Ann Hum Genet. 2016 Mar;80(2):81-7. doi: 10.1111/ahg.12146. Epub 2016 Feb 1.

Differentially Methylated Genomic Regions in Birth-Weight Discordant Twin Pairs.

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Computational Biology Group, Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark.
Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Macau, China.
Department of Information Engineering, University of Padova, Padova, Italy.
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
Unit of Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.


Poor nutrition during critical growth phases may alter the structural and physiologic development of vital organs thus "programming" the susceptibility to adult-onset diseases and disease-related health conditions. Epigenome-wide association studies have been performed in birth-weight discordant twin pairs to find evidence for such "programming" effects, but no significant results emerged. We further investigated this issue using a new computational approach: Instead of probing single genomic sites for significant alterations in epigenetic marks, we scan for differentially methylated genomic regions. Whole genome DNA methylation levels were measured in whole blood from 150 pairs of adult identical twins discordant for birth-weight. Intrapair differential DNA methylation was associated with qualitative (large or small) and quantitative (percentage) birth-weight discordance at each genomic site using regression models adjusting for age and sex. Based on the regression results, genomic regions with consistent alteration patterns of DNA methylation were located and tested for significant robustness using computational permutation tests. This yielded an interesting genomic region on chromosome 1, which is significantly differentially methylated for quantitative birth-weight discordance. The region covers two genes (TYW3 and CRYZ) both reportedly associated with metabolism. We conclude that prenatal conditions for birth-weight discordance may result in persistent epigenetic modifications potentially affecting even adult health.


Birth-weight discordance; DMR; DNA methylation; identical twins

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