Abstract
Perinatal light exposure predisposes towards health and behaviour in adulthood. Season of birth is associated with psychiatric, allergic, cardiovascular and metabolic problems. It has been proposed that early-life environmental light disrupts the development of biological rhythms which, in turn, influence later-life health. However, the mechanisms linking perinatal seasonal light to later-life biological rhythm and health in humans are unknown. In this study, we investigated the association between season of birth and epigenome-wide DNA methylation of two postmortem human brain regions (16 hypothalamus, 14 temporal cortex). We did not find statistically significant differences at the whole epigenome level, either because we lacked statistical power or that no association exists. However, when we examined 24 CpG sites that had the highest significance or differential methylation, we identified regions which may be associated with circadian rhythm entrainment, cholinergic neurotransmission and neural development. Amongst methylation of the core clock genes, we identified that hypothalamus Neuronal PAS Domain Protein 2 (NPAS2) gene has hypermethylated regions in long photoperiod-born individuals. In addition, we found nominal associations between season of birth and genes linked to chronotype and narcolepsy. Season of birth-related brain DNA methylation profile was different than a previously reported blood methylation profile, suggesting a tissue-specific mechanism of perinatal light programming. Overall, we are the first to analyse the relationship between season of birth and human brain DNA methylation. Further studies with larger sample sizes are required to confirm an imprinting effect of perinatal light on the circadian clock.
Highlights
The concept of The Developmental Origins of Health and Disease states that early-life environmental exposures may influence an individual’s behaviours and health in adulthood.[1]
We investigate epigenome-wide DNA methylation differences associated with seasonal photoperiod at birth in the human hypothalamus, which includes biological rhythm and sleep centres, and the inferior temporal gyrus (ITG), which has previously been reported as a candidate brain region for season of birth effect in a brain imaging study.[18]
We investigated associations between photoperiod at birth and human hypothalamus and ITG epigenome-wide DNA methylation patterns
Summary
The concept of The Developmental Origins of Health and Disease states that early-life environmental exposures may influence an individual’s behaviours and health in adulthood.[1]. If mice are reared under a summer solstice-like (16 h light:[8] h dark) photoperiod environment, the period of their circadian rhythm of gene expression, the period of their free-running activity rhythm in constant darkness and the period of individual neurons of their principal pacemaker, the suprachiasmatic nucleus (SCN) in the brain, all become shorter in adulthood compared to animals reared under a winter solstice-like (8 h light:[16] h dark) environment.[13]
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