Study Report

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Basic Info

Reference	Lai, Y. C., 2015 PMID: 25789810
Citation	Lai, Y. C., et al. (2015). "Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder." PLoS One 10(3): e0121245.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	candidate-gene association study
Sample Size	Sample I: 280 BD patients (200 BD-I, 80 BD-II), and 200 healthy controls; Sample II: 448 BD patients (262 BD-I, 186 BD-II) and 1770 healthy controls.
SNP/Region/Marker Size	sample I: 27 SNPs, sample II: 628,132 SNPs
Predominant Ethnicity	Mongloid
Population	Han Chinese
Gender	sample I: 137 male cases and 62 male controls; sample II: 198 male cases and 788 male controls
Age Group	adults : sample I: mean age=34.80 (sd=11.5) years for cases, mean age=47.30 (sd=8.7) years for controls; sample II: mean age=36.40 (sd=12.5) years for cases, mean age=46.20 (sd=14.7) years for controls

Detail Info

Sample Diagnosis	Diagnostic and Statistical Manual of Mental Disorders-IV (DSMIV)
Sample Status	Clinical patients who met the diagnostic criteria of bipolar I disorder (BD-I) or bipolar II disorder (BD-II) according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSMIV) were consecutively referred by psychiatrists in Taiwan from 2008 to 2012. Patients who diagnosed with schizophrenia, schizoaffective or substance-induced mood disorders and whose diagnoses were changed during the data collection period were excluded.
Technique	genotyping
Statistical Method	Single marker and gene-based 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 gene-gene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001).
Result Summary	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.

SNPs reported by this study for BD (count: 47)

SNP	Related Gene(s)	Statistical Values	Author Comments	Result Category
rs499922	RORB	Empirical P-value=0.042, OR=1.22	The marker showed associations with BD. The marker showed associations with BD.	Positive
rs1327836	RORB	Empirical P-value=0.003 in sample I, OR=1.75 in sample I	In sample I, one marker each in the RORA and RORB genes show...... In sample I, one marker each in the RORA and RORB genes showed associations with BD (P<0.05). Marker rs1327836 in RORB revealed association with BD in dominant model. More...	Positive
rs782908	RORA	Empirical P-value=0.03, OR=0.2	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs76824799	RORA	Empirical P-value=0.014, OR=0.74	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs74687025	RORA	Empirical P-value=0.018, OR=0.27	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs4775350	RORA	Empirical P-value=0.007, OR=0.43	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11631786	RORA	Empirical P-value=0.041, OR=0.8	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs17611535	RORB	Empirical P-value=0.027, OR=3.15	The most significant marker in each gene was rs17611535 in R...... The most significant marker in each gene was rs17611535 in RORB. More...	Positive
rs4774388	RORA	Empirical P-value=0.366; Empirical P-value=0.024 in sample I; OR=1.14; OR=1.53 in sample I	In sample I, one marker each in the RORA and RORB genes show...... In sample I, one marker each in the RORA and RORB genes showed associations with BD (P<0.05). The minor allele of rs4774388 in RORA had an increased risk for BD. The marker did not show association with BD in Sample II. More...	Positive
rs34720147	RORA	Empirical P-value=0.029, OR=1.19	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs2414686	RORA	Empirical P-value=0.014, OR=1.38	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs12910281	RORA	Empirical P-value=0.021, OR=1.38	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs8041466	RORA	Empirical P-value=0.021, OR=1.76	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11631432	RORA	Empirical P-value=0.026, OR=0.7	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs79995443	RORA	Empirical P-value=0.015, OR=0.69	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs72752802	RORA	Empirical P-value=0.034, OR=0.71	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs2899664	RORA	Empirical P-value=0.016, OR=1.25	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11855147	RORA	Empirical P-value=0.006, OR=0.66	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs35752305	RORA	Empirical P-value=0.035, OR=0.75	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs79610262	RORA	Empirical P-value=0.017, OR=0.7	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs75084363	RORA	Empirical P-value=0.005, OR=2.84	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs16943172	RORA	Empirical P-value=0.026, OR=0.78	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs16943117	RORA	Empirical P-value=0.017, OR=0.78	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs877228	RORA	Empirical P-value=0.034, OR=0.71	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs6494227	RORA	Empirical P-value=0.019, OR=0.71	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs12915776	RORA	Empirical P-value=0.004, OR=0.74	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs922781	RORA	Empirical P-value=0.021, OR=1.29	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11071558	RORA	Empirical P-value=0.005, OR=0.72	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs17270446	RORA	Empirical P-value=0.04, OR=0.38	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs1963497	RORA	Empirical P-value=0.044, OR=0.77	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs12594188	RORA	Empirical P-value=0.025, OR=0.81	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11639084	RORA	Empirical P-value=0.002, OR=0.69	The most significant marker in each gene was rs11639084 in R...... The most significant marker in each gene was rs11639084 in RORA. More...	Positive
rs11071557	RORA	Empirical P-value=0.003, OR=0.71	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs10519067	RORA	Empirical P-value=0.021, OR=0.74	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs12900122	RORA	Empirical P-value=0.016, OR=0.74	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs8025689	RORA	Empirical P-value=0.007, OR=0.72	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs9302215	RORA	Empirical P-value=0.044, OR=0.84	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs1482057	RORA	Empirical P-value=0.023, OR=1.27	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs13329238	RORA	Empirical P-value=0.03, OR=1.75	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs17237353	RORA	Empirical P-value=0.008, OR=0.72	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs1020729	RORA	Empirical P-value=0.043, OR=0.85	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs1020730	RORA	Empirical P-value=0.014, OR=0.78	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs11632600	RORA	Empirical P-value=0.01, OR=1.9	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs75981965	RORA	Empirical P-value=0.028, OR=0.68	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs339998	RORA	Empirical P-value=0.03, OR=1.3	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs2553236	RORA	Empirical P-value=0.035, OR=0.63	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive
rs8041381	RORA	Empirical P-value=0.022, OR=1.31	One of 45 SNPs showed associations with BD. One of 45 SNPs showed associations with BD.	Positive

Genes reported by this study for BD (count: 2)

Gene	Statistical Values/Author Comments	Result Category
RORB	Our results support for the involvement of RORs genes in the risk of developing BD. Our results support for the involvement of RORs genes in the risk of developing BD.	Positive
RORA	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. Our results support for the involvement of RORs genes in the risk of developing BD.	Positive