Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig-Maximilians Universität München (LMU), Munich, Germany.
Cancer and Disease Epigenetics Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, 3052, Victoria, Australia.
Sci Rep. 2017 Oct 30;7(1):14349. doi: 10.1038/s41598-017-13099-4.
Adiposity and obesity result from the interaction of genetic variation and environmental factors from very early in life, possibly mediated by epigenetic processes. Few Epigenome-Wide-Association-Studies have identified DNA-methylation (DNAm) signatures associated with BMI and body composition in children. Body composition by Bio-Impedance-Analysis and genome-wide DNAm in whole blood were assessed in 374 pre-school children from four European countries. Associations were tested by linear regression adjusted for sex, age, centre, education, 6 WBC-proportions according to Houseman and 30 principal components derived from control probes. Specific DNAm variants were identified to be associated with BMI (212), fat-mass (230), fat-free-mass (120), fat-mass-index (24) and fat-free-mass-index (15). Probes in genes SNED1(IRE-BP1), KLHL6, WDR51A(POC1A), CYTH4-ELFN2, CFLAR, PRDM14, SOS1, ZNF643(ZFP69B), ST6GAL1, C3orf70, CILP2, MLLT4 and ncRNA LOC101929268 remained significantly associated after Bonferroni-correction of P-values. We provide novel evidence linking DNAm with (i) altered lipid and glucose metabolism, (ii) diabetes and (iii) body size and composition in children. Both common and specific epigenetic signatures among measures were also revealed. The causal direction with phenotypic measures and stability of DNAm variants throughout the life course remains unclear and longitudinal analysis in other populations is required. These findings give support for potential epigenetic programming of body composition and obesity.
肥胖是由遗传变异和生命早期环境因素相互作用引起的，可能由表观遗传过程介导。少数全基因组关联研究已经确定了与儿童 BMI 和身体成分相关的 DNA 甲基化（DNAm）特征。在来自四个欧洲国家的 374 名学龄前儿童中，通过生物阻抗分析评估身体成分和全血的全基因组 DNAm。通过线性回归调整性别、年龄、中心、教育、根据 Houseman 的 6 个白细胞比例和从对照探针中得出的 30 个主成分，对关联进行了测试。确定了与 BMI（212）、脂肪量（230）、去脂肪量（120）、脂肪量指数（24）和去脂肪量指数（15）相关的特定 DNAm 变体。在基因 SNED1（IRE-BP1）、KLHL6、WDR51A（POC1A）、CYTH4-ELFN2、CFLAR、PRDM14、SOS1、ZNF643（ZFP69B）、ST6GAL1、C3orf70、CILP2、MLLT4 和 ncRNA LOC101929268 中的探针在经过 Bonferroni 校正后仍然与 P 值显著相关。我们提供了新的证据，将 DNAm 与（i）改变的脂质和葡萄糖代谢、（ii）糖尿病和（iii）儿童的身体大小和成分联系起来。还揭示了在各种测量方法中存在共同和特定的表观遗传特征。与表型测量的因果关系以及整个生命过程中 DNAm 变体的稳定性仍不清楚，需要在其他人群中进行纵向分析。这些发现为身体成分和肥胖的潜在表观遗传编程提供了支持。
