Seasonal influences on DNA methylation at birth or at sampling time and their interaction with psychosis risk

Season at birth has been associated with increased risk for psychotic disorders. Epigenetic markers, which can be influenced by environmental exposures, may help to understand the mechanisms of seasonal effects.

To investigate two types of seasonal influences on DNA methylation: season of sampling and season of birth, and to test whether these seasonal effects interact with psychotic disorder risk.

We used two cohorts: a sample of newborns from the Norwegian Mother, Father, and Child Study (MoBa) and a sample of adult participants from the Thematically Organized Psychosis (TOP) sample. The cosinor function from the R package "seasons" was used to identify seasonally methylated positions (SMPs) associated with season of birth and season of sampling. Meta-analyses were performed between results from the MoBa birth cohort, and the TOP healthy adults samples for both season of birth and season of sampling. Interaction analyses between season of birth/season of sampling and psychosis status were conducted in the TOP cohort.

In the meta-analysis of healthy controls from our cohorts, we identified six SMPs (IQSEC1, CACNA2D3, TMEM86B, CNOT3, ZNF250, and ARHGEF3) and two SMPs (ZNF250 and SLC6A19) associated with season of sampling and season of birth, respectively. In the interaction analysis, one significant SMP (cg13593913,) was found to be associated with a psychosis diagnosis and season of birth.

In our study, we show a potential interaction between season of birth and psychosis diagnosis. These findings highlight the importance of considering the season of birth and season of sampling in epigenetic research.