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Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system
Article first published online: 25 FEB 2009
© 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard
Volume 11, Issue 2, pages 215–220, March 2009
How to Cite
Severino, G., Manchia, M., Contu, P., Squassina, A., Lampus, S., Ardau, R., Chillotti, C. and Del Zompo, M. (2009), Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBα gene, a critical component of the circadian clock system. Bipolar Disorders, 11: 215–220. doi: 10.1111/j.1399-5618.2009.00667.x
- Issue published online: 25 FEB 2009
- Article first published online: 25 FEB 2009
- Received 13 December 2007, revised and accepted for publication 23 May 2008
- age at onset;
- circadian rhythms;
- complex disease;
- isolated populations;
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.