Previous studies suggested that both maladaptive stress response and circadian dysregulation
might have a role in the background of migraine. However, effects of circadian genes
on migraine have not been tested yet. In the present study, we investigated the main
effect of rs10462028 of the circadian locomotor output cycles kaput (CLOCK) gene and
its interaction with different stress factors on migraine. In our cross-sectional
study 2,157 subjects recruited from Manchester and Budapest completed the ID-Migraine
questionnaire to detect migraine type headaches (migraineID). Additional stress factors
were assessed by a shortened version of the Childhood Trauma Questionnaire, the List
of Threatening Experiences questionnaire, and a validated questionnaire to identify
financial difficulties. Rs10462028 showed no main genetic effect on migraineID. However,
chronic stress indexed by financial difficulties showed a significant interaction
effect with rs10462028 (p = 0.006 in recessive model) on migraineID. This result remained
significant after correction for lifetime bipolar and unipolar depression and was
replicated in both subsamples, although only a trend effect was reached after Bonferroni-correction,
which is the strictest correction not considering interdependences. Childhood adversity
(CHA) and Recent negative life events (RLE) showed no significant gene × stress interaction
with rs10462028. In addition, in silico analysis demonstrated that the genetic region
tagged by rs10462028 alters the binding of several miRNAs. Our exploratory study suggests
that variations in the CLOCK gene, with moderating effect on gene function through
miRNA binding, in interaction with financial difficulties might influence the risk
of migraine-type headaches. Thus, financial hardship as a chronic stress factor may
affect migraine through altering circadian rhythms.
