Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder

Yin Chieh Lai, Chung Feng Kao, Mong Liang Lu, Hsi Chung Chen, Po Yu Chen, Chien Hsiun Chen, Winston W. Shen, Jer Yuarn Wu, Ru Band Lu, Po Hsiu Kuo

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Several genes that are involved in the regulation of circadian rhythms are implicated in the susceptibility to bipolar disorder (BD). The current study aimed to investigate the relationships between genetic variants in NR1D1 RORA, and RORB genes and BD in the Han Chinese population. We conducted a case-control genetic association study with two samples of BD patients and healthy controls. Sample I consisted of 280 BD patients and 200 controls. Sample II consisted of 448 BD patients and 1770 healthy controls. 27 single nucleotide polymorphisms in the NR1D1, RORA, and RORB genes were genotyped using GoldenGate VeraCode assays in sample I, and 492 markers in the three genes were genotyped using Affymetrix Genome-Wide CHB Array in sample II. Single marker and genebased association analyses were performed using PLINK. A combined p-value for the joining effects of all markers within a gene was calculated using the rank truncated product method. Multifactor dimensionality reduction (MDR) method was also applied to test genegene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001). In sample I, the associations with BD were observed for rs4774388 in RORA (OR = 1.53, empirical p-value, P = 0.024), and rs1327836 in RORB (OR = 1.75, P = 0.003). In Sample II, there were 45 SNPs showed associations with BD, and the most significant marker in RORA was rs11639084 (OR = 0.69, P = 0.002), and in RORB was rs17611535 (OR = 3.15, P = 0.027). A combined p-value of 1.6x10 -6, 0.7, and 1.0 was obtained for RORA, RORB and NR1D1, respectively, indicting a strong association for RORA with the risk of developing BD. A four way interaction was found among markers in NR1D1, RORA, and RORB with the testing accuracy 53.25% and a cross-validation consistency of 8 out of 10. In sample II, 45 markers had empirical p-values less than 0.05. The most significant markers in RORA and RORB genes were rs11639084 (OR = 0.69, P = 0.002), and rs17611535 (OR = 3.15, P = 0.027), respectively. Gene-based association was significant for RORA gene (P = 0.0007). Our results support for the involvement of RORs genes in the risk of developing BD. Investigation of the functional properties of genes in the circadian pathway may further enhance our understanding about the pathogenesis of bipolar illness.

Original languageEnglish
Article numbere0121245
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 19 2015

Fingerprint

Bipolar Disorder
Genes
genes
sampling
Association reactions
Single Nucleotide Polymorphism
Multifactor Dimensionality Reduction
Genetic Association Studies
Circadian Rhythm
circadian rhythm
single nucleotide polymorphism
Polymorphism
functional properties
Joining
pathogenesis
Assays
testing
Genome
Nucleotides
genome

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lai, Y. C., Kao, C. F., Lu, M. L., Chen, H. C., Chen, P. Y., Chen, C. H., ... Kuo, P. H. (2015). Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder. PLoS One, 10(3), [e0121245]. https://doi.org/10.1371/journal.pone.0121245

Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder. / Lai, Yin Chieh; Kao, Chung Feng; Lu, Mong Liang; Chen, Hsi Chung; Chen, Po Yu; Chen, Chien Hsiun; Shen, Winston W.; Wu, Jer Yuarn; Lu, Ru Band; Kuo, Po Hsiu.

In: PLoS One, Vol. 10, No. 3, e0121245, 19.03.2015.

Research output: Contribution to journalArticle

Lai, YC, Kao, CF, Lu, ML, Chen, HC, Chen, PY, Chen, CH, Shen, WW, Wu, JY, Lu, RB & Kuo, PH 2015, 'Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder', PLoS One, vol. 10, no. 3, e0121245. https://doi.org/10.1371/journal.pone.0121245
Lai, Yin Chieh ; Kao, Chung Feng ; Lu, Mong Liang ; Chen, Hsi Chung ; Chen, Po Yu ; Chen, Chien Hsiun ; Shen, Winston W. ; Wu, Jer Yuarn ; Lu, Ru Band ; Kuo, Po Hsiu. / Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder. In: PLoS One. 2015 ; Vol. 10, No. 3.
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