MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, BS8 2BN UK.
Child and Adolescent Mental Health, Population Policy and Practice, Institute of Child Health, UCL, London, UK.
Clin Epigenetics. 2017 Oct 27;9:120. doi: 10.1186/s13148-017-0418-3. eCollection 2017.
Eating disorders (ED) are chronic psychiatric disorders, common amongst women of reproductive age. ED in pregnancy are associated with poor nutrition and abnormal intrauterine growth. Increasing evidence also shows offspring of women with ED have adverse developmental and birth outcomes. We sought to carry out the first study investigating DNA methylation in offspring of women with ED. We compared cord blood DNA methylation in offspring of women with active ED ( = 21), past ED ( = 43) and age- and social class-matched controls ( = 126) as part of the Avon Longitudinal Study of Parents and Children.
Offspring of women with both active and past ED had lower whole-genome methylation compared to controls (active ED 49.1% (95% confidence intervals 50.5-47.7%), past ED 49.2% (95% CI 50.7-47.7.0%), controls 52.4% (95% CI 53.0%-51.0%)). Amongst offspring of ED women, those born to women with restrictive-type and purging-type ED had lower methylation levels compared to those of controls. Offspring of women with an active restrictive ED in pregnancy had lower whole-genome methylation compared to offspring of women with past restrictive ED. We observed decreased methylation at the locus in offspring of women with active pregnancy ED (effect size (ES) = - 0.124, = 6.94 × 10) and increased methylation at the locus in offspring of women with past ED (ES = 0.07, = 3.74 × 10) compared to controls.
Maternal active and past ED are associated with differences in offspring whole-genome methylation. Our results show altered DNA methylation in loci relevant to metabolism; these might be biomarkers of disrupted metabolic pathways in offspring of ED mothers. Further work is needed to examine potential mechanisms and functional outcomes of the observed methylation patterns.
饮食失调（ED）是一种慢性精神疾病，在育龄妇女中较为常见。妊娠期 ED 与营养不良和宫内生长异常有关。越来越多的证据表明，ED 女性的后代在发育和出生方面存在不良结局。我们试图进行第一项研究，以调查 ED 女性后代的 DNA 甲基化。我们比较了患有活跃 ED（=21）、既往 ED（=43）和年龄及社会阶层匹配对照（=126）的女性脐带血 DNA 甲基化情况，这是阿冯纵向父母和儿童研究的一部分。
与对照组相比，患有活跃和既往 ED 的女性后代的全基因组甲基化水平较低（活跃 ED 为 49.1%（95%置信区间 50.5-47.7%），既往 ED 为 49.2%（95%置信区间 50.7-47.7%），对照组为 52.4%（95%置信区间 53.0%-51.0%））。在 ED 女性的后代中，与对照组相比，患有限制型和清除型 ED 的女性后代的甲基化水平较低。妊娠期间患有活跃性限制型 ED 的女性的后代全基因组甲基化水平低于既往限制型 ED 的女性后代。我们观察到，与对照组相比，患有活跃妊娠 ED 的女性后代中的 位点的甲基化减少（效应大小（ES）=-0.124， =6.94×10），而患有既往 ED 的女性后代中的 位点的甲基化增加（ES=0.07， =3.74×10）。
母亲的活跃期和既往 ED 与后代全基因组甲基化的差异有关。我们的研究结果表明，代谢相关基因座的 DNA 甲基化发生改变；这些可能是 ED 母亲后代代谢途径紊乱的生物标志物。需要进一步研究以检查观察到的甲基化模式的潜在机制和功能结果。
