Circadian genes and lithium response in bipolar disorders: associations with PPARGC1A (PGC‐1α) and RORA

Preliminary studies suggest that lithium (Li) response might be associated with some circadian gene polymorphisms, we therefore performed a pharmacogenetic study on the core clock genes in two independent samples suffering from bipolar disorder (BD) and thoroughly characterized for their Li response...

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Bibliographic Details
Published in:Genes, brain and behavior brain and behavior, 2016-09, Vol.15 (7), p.660-668
Main Authors: Geoffroy, P. A., Etain, B., Lajnef, M., Zerdazi, E‐H., Brichant‐Petitjean, C., Heilbronner, U., Hou, L., Degenhardt, F., Rietschel, M., McMahon, F. J., Schulze, T. G., Jamain, S., Marie‐Claire, C., Bellivier, F.
Format: Article
Language:English
Subjects:
Adult
Biochemistry, Molecular Biology
Bipolar Disorder
Bipolar Disorder - drug therapy
Bipolar Disorder - genetics
Bipolar Disorder - metabolism
circadian genes
Circadian Rhythm
Circadian Rhythm - genetics
circadian rhythms
clock genes
Female
Genes
Genetic Association Studies
Genetic Predisposition to Disease
Genomics
Heat-Shock Proteins
Heat-Shock Proteins - genetics
Humans
Life Sciences
lithium carbonate
Lithium Compounds
Lithium Compounds - therapeutic use
lithium salts
Male
Middle Aged
Nuclear Receptor Subfamily 1, Group F, Member 1
Nuclear Receptor Subfamily 1, Group F, Member 1 - genetics
Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
Polymorphism, Single Nucleotide
Transcription Factors
Transcription Factors - genetics
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Summary:Preliminary studies suggest that lithium (Li) response might be associated with some circadian gene polymorphisms, we therefore performed a pharmacogenetic study on the core clock genes in two independent samples suffering from bipolar disorder (BD) and thoroughly characterized for their Li response. Two independent Caucasian samples (165 and 58 bipolar patients) treated with Li were selected from samples recruited in a French multicenter study and assessed for their Li response using the Alda scale. The two samples were genotyped using the Human660 (H660) and OmniExpress (OE) BeadChips and gene‐based association analyses of 22 core clock genes were conducted. In the first sample (H660 chip), the RAR‐related orphan receptor‐a gene (RORA) and the Peroxisome Proliferator‐Activated Receptor Gamma, Coactivator 1 Alpha gene (PPARGC1A or PGC‐1α) were significantly associated with the Li response (empirical P‐value = 0.0015 and 0.04, respectively), and remained significant only for RORA after Bonferroni correction. In the second sample (OE chip), PPARGC1A was significantly associated with the Li response (empirical P‐value = 0.04), and did not remain significant after Bonferroni correction. PPARGC1A is a master regulator of mitochondrial function and a key component of the endogenous clock that stimulates the expression of Bmal1 and Rev‐erb‐alpha through coactivation of RORA. Although the observed associations deserve further replication and investigation, our results suggest genetic associations between Li response and these two close biological partners: PPARGC1A and RORA involved in circadian rhythms and bioenergetics processes in Li response. Genetic associations between lithium response and two close biological circadian partners : PPARGC1A (PGC‐1α) and RORA.
ISSN:1601-1848
1601-183X
DOI:10.1111/gbb.12306