Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system


  • The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript.

Giovanni Severino, MD, Section of Clinical Pharmacology, Department of Neurosciences, University of Cagliari, P.O. San Giovanni di Dio, Via Ospedale 46, 09124 Cagliari, Italy.
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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.