• age at onset;
  • circadian rhythms;
  • complex disease;
  • isolated populations;
  • NR1D1;
  • REV-ERBα

Objective:  The aim of our study was to investigate the association between REV-ERBα gene (NR1D1) single nucleotide polymorphisms (SNPs) and bipolar disorder (BP) in a case-control sample of Sardinian ancestry and evaluate its effect on age at onset (AAO) of BP.

Methods:  We genotyped SNPs rs12941497 (SNP1) and rs939347 (SNP2), located, respectively, in the first intron and in the 5′UTR region of the gene, in a sample comprised of 300 bipolar patients and 300 healthy controls of Sardinian ancestry. We also studied AAO by means of admixture analysis, obtaining a cutoff point of age 22 and then carrying out association analysis between the two AAO groups.

Results:  In the case-control comparison, single marker analysis showed no association for any of the SNPs tested. Haplotype analysis showed a nominally significant association for two haplotypes of SNPs 1-2. Comparing the early- and later-onset groups, nominal association was found for SNP1. Haplotype analysis showed that one haplotype was nominally associated with the later-onset group.

Conclusions:  Our results, indicating a nominal association of the REV-ERBα gene with BP, suggest a possible role of REV-ERBα in the pathogenesis of BP. Further investigation of larger independent samples and different populations is warranted.