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Updated: Oct 22, 2025

Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
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PER Gene Family Polymorphisms in Relation to Cluster Headache and Circadian Rhythm in Sweden

Felicia Jennysdotter Olofsgård1, Caroline Ran1, Carmen Fourier1

  • 1Department of Neuroscience, Karolinska Institutet, 171 65 Stockholm, Sweden.

Brain Sciences
|August 27, 2021
PubMed

Insights

This study found no link between specific PER gene variants and cluster headache (CH) or its daily timing in Swedish individuals. These genetic markers do not appear to influence CH occurrence or diurnal patterns.

Area of Science:

  • Neuroscience
  • Genetics
  • Chronobiology

Background:

  • Cluster headache (CH) is a severe cephalalgia characterized by distinct diurnal patterns in attack occurrence.
  • Circadian rhythm genes, particularly Period Circadian Regulator (PER) genes (PER1, PER2, PER3), are hypothesized to influence CH rhythmicity.

Purpose of the Study:

  • To investigate the association between specific genetic variants in PER1, PER2, and PER3 genes and cluster headache in a Swedish population.
  • To determine if these genetic variants are linked to the diurnal rhythmicity of CH attacks or diurnal preference.

Main Methods:

  • Genotyping of six PER gene markers (one indel and five SNPs) in a Swedish CH case-control cohort.
  • Analysis using logistic regression to assess the association between genetic variants and CH.
  • Examination of allele frequencies in relation to diurnal rhythmicity and diurnal preference.

Main Results:

  • No statistically significant association was found between any of the six genotyped PER variants and cluster headache.
  • No significant differences in allele frequency were observed for patients reporting diurnal rhythmicity or diurnal preference.
  • The p-values for the tested genetic markers ranged from 0.416 to 0.907, indicating no significant genetic link.

Conclusions:

  • The studied PER1, PER2, and PER3 genetic variants do not appear to play a role in the pathogenesis of cluster headache in the Swedish population.
  • These specific genetic variants are not associated with the diurnal phenotype observed in cluster headache patients.
  • Further research may be needed to explore other genetic factors influencing CH and its circadian features.

Keywords:
clock genesdiurnal preferencediurnal rhythmicitygeneticspain

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