Al-Hinai Maymona, Baylin Ana, Peterson Karen E, Song Peter X K, Téllez-Rojo Martha M, Torres-Olascoaga Libni A, Cantoral Alejandra, Dolinoy Dana C, Goodrich Jaclyn M, Jansen Erica C
Department of Food Science and Human Nutrition, Sultan Qaboos University College of Agriculture and Marine Science, Muscat, Oman.
Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Sleep. 2025 Aug 14;48(8). doi: 10.1093/sleep/zsaf116.
This study aims first, to evaluate the longitudinal sex-specific association between iron status and objective sleep outcomes; second, to explore the cross-sectional relationship between iron status and blood leukocyte DNA methylation of key circadian genes during adolescence.
Iron status for 371 adolescents from the Mexico City-based ELEMENT cohort was estimated using serum ferritin levels. Sleep duration, sleep midpoint, sleep fragmentation, and movement index during both weekdays and weekends were measured objectively using 7-day wrist actigraphy collected at two timepoints. The Infinium MethylationEPIC BeadChip was used to measure DNA methylation of circadian genes, and data was extracted from 525 CpG sites within 12 key circadian genes. Sex-stratified linear mixed-effects regression with random intercepts were used to assess the relationship between ferritin tertiles and sleep outcomes. The association between ferritin tertiles and DNA methylation was evaluated by linear regression. The Cauchy combination test was used to combine results from individual CpG sites for each gene. A false discovery rate was used to account for multiple comparisons.
Females with ferritin levels in the first tertile had 1.35% (95% CI: 0.21, 2.50) higher sleep fragmentation during weekdays compared to the third tertile; males with ferritin levels in the first tertile had later sleep timing during the weekends (β: 0.59 decimal hour, 95% CI: 0.05, 1.13). Among females, lower ferritin levels were associated with DNA methylation differences in CLOCK, PER1, and RORC (FDR = 0.0392).
Differences in ferritin levels may be linked to lower sleep quality and epigenetic modifications in some circadian genes, especially in females.
本研究旨在首先评估铁状态与客观睡眠结果之间的纵向性别特异性关联；其次，探讨青春期铁状态与关键昼夜节律基因的血液白细胞DNA甲基化之间的横断面关系。
使用血清铁蛋白水平估计来自墨西哥城ELEMENT队列的371名青少年的铁状态。使用在两个时间点收集的7天腕部活动记录仪客观测量工作日和周末的睡眠时间、睡眠中点、睡眠碎片化和活动指数。Infinium MethylationEPIC BeadChip用于测量昼夜节律基因的DNA甲基化，并从12个关键昼夜节律基因内的525个CpG位点提取数据。使用具有随机截距的性别分层线性混合效应回归来评估铁蛋白三分位数与睡眠结果之间的关系。通过线性回归评估铁蛋白三分位数与DNA甲基化之间的关联。Cauchy组合检验用于合并每个基因的各个CpG位点的结果。使用错误发现率来考虑多重比较。
与第三三分位数相比，第一三分位数铁蛋白水平的女性在工作日的睡眠碎片化程度高1.35%（95%CI：0.21，2.50）；第一三分位数铁蛋白水平的男性在周末的睡眠时间较晚（β：0.59小数小时，95%CI：0.05，1.13）。在女性中，较低的铁蛋白水平与CLOCK、PER1和RORC中的DNA甲基化差异相关（FDR = 0.0392）。
铁蛋白水平的差异可能与睡眠质量降低和某些昼夜节律基因的表观遗传修饰有关，尤其是在女性中。
