BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Kripke, D. F.,2009 PMID: 19166596
Citation	Kripke, D. F., C. M. Nievergelt, et al. (2009). Circadian polymorphisms associated with affective disorders. J Circadian Rhythms 7: 2.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	Bipolar probands and families:444 nuclear families including 561 affected offspring(bipolar type 1 disorder, bipolar type 2 disorder, and schizoaffective (bipolar type) patients);Bipolar probands and the morningness-eveningness quantitative trait:130 unrelated research volunteers;Unipolar major depression affected sibling pairs:298 individuals in 149 families (89 concordant and 60 discordant sibpairs);Sleep Clinic sample:360 patients suffered from depression
SNP/Region/Marker Size	260 SNPs
Predominant Ethnicity	Caucasian

Detail Info

Sample Status	Four groups of subjects were recruited from several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear families, 2) unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3) sib pairs fromthe GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4) a sleep clinic patient group who frequently suffered from depression.
Technique	genotyping
Statistical Method	transmission-disequilibrium test (TDT)
Result Summary	RESULTS: In NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005). Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample. CONCLUSION: Along with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P < 0.05), whereas 15 would be expected by chance, indicating that many represented false discoveries (Type II errors). Some evidence of replication has been gathered, but more studies are needed to ascertain if circadian gene polymorphisms contribute to susceptibility to affective disorders.

SNPs reported by this study for BD (count: 17)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs3805148	CLOCK TMEM165	C/A		TDT: In BP: OR=1.294, CHISQ=7.442, P-value = 0.0064, empirical P-value = 0.0092, corrected empirical P-value = 0.6291	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs4510078	CSNK1D SLC16A3	A/G		TDT: In BP: OR=0.474, CHISQ=7.143, P-value = 0.0075, empirical P-value = 0.0175, corrected empirical P-value = 0.6942	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2585405	PER1 PGAP3	G/C		TDT: In BP: OR=0.735, CHISQ=4.734, P-value = 0.0296, empirical P-value = 0.0457, corrected empirical P-value = 0.9881	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs3736544	CLOCK TMEM165	A/G		TDT: In BP: OR=0.818, CHISQ=5.11, P-value = 0.0238, empirical P-value = 0.0241, corrected empirical P-value = 0.9728	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs6850524	CLOCK	C/G		TDT: In BP: OR=0.823, CHISQ=4.864, P-value = 0.0274, empirical P-value = 0.0322, corrected empirical P-value = 0.984	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs7732671	PPARGC1B	C/G		TDT: In BP: OR=1.548, CHISQ=4.944, P-value = 0.0262, empirical P-value = 0.0213, corrected empirical P-value = 0.9811	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs4663868	PER2	T/C		TDT: In BP: OR=1.574, CHISQ=6.914, P-value = 0.0086, empirical P-value = 0.0171, corrected empirical P-value = 0.733	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs4864542	CLOCK	G/C		TDT: In BP: OR=1.288, CHISQ=7.672, P-value = 0.0056, empirical P-value = 0.0102, corrected empirical P-value = 0.5759	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs1562313	NPAS2	A/G		TDT: In BP: OR=1.261, CHISQ=4.957, P-value = 0.026, empirical P-value = 0.0484, corrected empirical P-value = 0.9803	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2071427	NR1D1 THRA	A/G		TDT: In BP: OR=0.746, CHISQ=9.452, P-value = 0.0021, empirical P-value = 0.0019, corrected empirical P-value = 0.2852	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs12504300	CLOCK	C/G		TDT: In BP: OR=1.362, CHISQ=7.669, P-value = 0.0056, empirical P-value = 0.0094, corrected empirical P-value = 0.5775	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs12648271	CLOCK	C/G		TDT: In BP: OR=1.247, CHISQ=4.951, P-value = 0.0261, empirical P-value = 0.0369, corrected empirical P-value = 0.9806	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2304672	PER2	G/C		TDT: In BP: OR=1.6, CHISQ=7.615, P-value = 0.0058, empirical P-value = 0.0123, corrected empirical P-value = 0.5972	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2314339	NR1D1 THRA	T/C		TDT: In BP: OR=0.612, CHISQ=13.71, P-value = 0.0002, empirical P-value = 0.0005, corrected empirical P-value = 0.0338	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2269457	NR1D1 THRA	G/A		TDT: In BP: OR=0.799, CHISQ=4.803, P-value = 0.0284, empirical P-value = 0.0292, corrected empirical P-value = 0.9861	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs2304669	PER2	G/A		TDT: In BP: OR=0.784, CHISQ=4.349, P-value = 0.037, empirical P-value = 0.0416, corrected empirical P-value = 0.9945	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
rs939348	THRA	T/C		TDT: In BP: OR=0.787, CHISQ=6.091, P-value = 0.0136, empirical P-value = 0.0224, corrected empirical P-value = 0.8729	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive

Genes reported by this study for BD (count: 8)

Gene	Statistical Values/Author Comments	Result Category
NPAS2	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
PER2	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
PER1	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
CSNK1D	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
CLOCK	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
THRA	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
NR1D1	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive
PPARGC1B	Significant association was observed in the BP group. Significant association was observed in the BP group.	Positive