A distinctive DNA methylation pattern in insufficient sleep

Abstract

Short sleep duration or insomnia may lead to an increased risk of various psychiatric and cardio-metabolic conditions. Since DNA methylation plays a critical role in the regulation of gene expression, studies of differentially methylated positions (DMPs) might be valuable for understanding the mechanisms underlying insomnia. We performed a cross-sectional genome-wide analysis of DNA methylation in relation to self-reported insufficient sleep in individuals from a community-based sample (79 men, aged 39.3 ± 7.3), and in relation to shift work disorder in an occupational cohort (26 men, aged 44.9 ± 9.0). The analysis of DNA methylation data revealed that genes corresponding to selected DMPs form a distinctive pathway: “Nervous System Development” (FDR P value < 0.05). We found that 78% of the DMPs were hypomethylated in cases in both cohorts, suggesting that insufficient sleep may be associated with loss of DNA methylation. A karyoplot revealed clusters of DMPs at various chromosomal regions, including 12 DMPs on chromosome 17, previously associated with Smith-Magenis syndrome, a rare condition comprising disturbed sleep and inverse circadian rhythm. Our findings give novel insights into the DNA methylation patterns associated with sleep loss, possibly modifying processes related to neuroplasticity and neurodegeneration. Future prospective studies are needed to confirm the observed associations.

Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer’s Disease and the Blood-Brain Barrier

“…Indeed, the brain eats itself after short and chronic sleep loss via microglial activation and astrocytic phagocytosis of synaptic elements [ 1 ]. Insufficient sleep leads to sterile inflammation in the absence of infection [ 2 , 3 , 4 ] and to enhanced permeability of the blood–brain barrier (BBB) [ 3 , 5 ]. The total sleep deprivation of rats produced their death [ 6 ].…”

Differentially methylated regions in bipolar disorder and suicide

“…An intriguing component that we were unable to explore due to limitations with our patient data was the link between DNA methylation and circadian rhythms. It is well known that circadian rhythms and sleep can influence DNA methylation patterns (Gaine, Chatterjee, & Abel, ; Lahtinen et al, ). Furthermore, sleep disturbances are increased in individuals with psychiatric disorders (Watson et al, ) and circadian rhythms are thought to regulate mood (McClung, ), therefore our BD cohort may have had increased aberrant sleep patterns.…”

Differential DNA methylation in recovery from shift work disorder

“…11 shift workers (18% women, age = 49.2 ± 9.1 years) lacking the symptoms were deemed as controls. The SWD status assessment is described in detail in our previous studies 12 , 31 .…”

“…Outside of oncology and studies focused on aging, longitudinal studies in humans are scarce and, to our best knowledge, there are no studies of DNAme on sleep disorders with longitudinal data. Earlier, we reported the results of a cross-sectional genome-wide analysis of DNAme in two cohorts—a community-based sample and an occupational cohort of shift workers 12 . In general, sleep disorders, tiredness, and an increased risk of occupational injuries are associated with working in shifts 13 , 14 .…”