A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder

Francesco Benedetti, Sara Dallaspezia, Cristina Colombo, Adele Pirovano, Elena Marino, Enrico Smeraldi

Research output: Contribution to journalArticle


Age at onset of bipolar disorder might represent the penetrance of the system for specific genetic liability involved in the genesis of the illness. Genetic factors influencing age at onset have been shown to play a role in shaping core characteristics of the illness, such as severity and pattern of recurrence. Genetic variants of genes regulating the circadian clock could contribute to define endophenotypes of bipolar disorder, and have been associated with clinical features of the disease. The coding region of Per3 gene contains a variable-number tandem-repeat (VNTR) polymorphism which has been associated with diurnal preference, sleep structure and sleep homeostasis in healthy subjects. In a homogeneous sample of 99 patients affected by bipolar disorder type I we observed that Per3 VNTR influenced age at onset of illness: earlier age at onset in homozygote carriers of Per35 variant, later in homozygotes for Per34, and intermediate in heterozygotes. Allele frequencies were not significantly different from those reported in healthy subjects. Results need to be confirmed in larger samples, but warrant interest for the variants of molecular clock genes as possible endophenotypes of bipolar disorder.

Original languageEnglish
Pages (from-to)184-187
Number of pages4
JournalNeuroscience Letters
Issue number2
Publication statusPublished - Nov 14 2008


  • Age at onset
  • Biological clock
  • Bipolar disorder
  • Endophenotype
  • Per3 gene
  • VNTR polymorphism

ASJC Scopus subject areas

  • Neuroscience(all)

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