Circadian polymorphisms associated with affective disorders

Daniel F Kripke; Caroline M Nievergelt; EJ Joo; Tatyana Shekhtman; John R Kelsoe

doi:10.1186/1740-3391-7-2

Figures & Tables

Table 1

Polymorphisms associated with bipolar disorder

Gene	CHR	SNP	A1	A2	MAF	T	U	OR	CHISQ	P	EMP1	EMP2
*NPAS2*	2	rs1562313	A	G	0.213	208	165	1.261	4.957	0.0260	0.0484	0.9803
*PER2*	2	rs4663868	T	C	0.071	85	54	1.574	6.914	0.0086	0.0171	0.7330
*PER2*	2	rs2304669	G	A	0.164	131	167	0.784	4.349	0.0370	0.0416	0.9945
*PER2*	2	rs2304672	G	C	0.073	88	55	1.600	7.615	0.0058	0.0123	0.5972
*CLOCK*	4	rs3805148	C	A	0.366	255	197	1.294	7.442	0.0064	0.0092	0.6291
*CLOCK*	4	rs3736544	A	G	0.373	229	280	0.818	5.110	0.0238	0.0241	0.9728
*CLOCK*	4	rs12504300	C	G	0.282	188	138	1.362	7.669	0.0056	0.0094	0.5775
*CLOCK*	4	rs4864542	G	C	0.364	273	212	1.288	7.672	0.0056	0.0102	0.5759
*CLOCK*	4	rs12648271	C	G	0.285	227	182	1.247	4.951	0.0261	0.0369	0.9806
*CLOCK*	4	rs6850524	C	G	0.424	232	282	0.823	4.864	0.0274	0.0322	0.9840
*PPARGC1B*	5	rs7732671	C	G	0.068	65	42	1.548	4.944	0.0262	0.0213	0.9811
*PER1*	17	rs2585405	G	C	0.104	86	117	0.735	4.734	0.0296	0.0457	0.9881
*THRA*	17	rs939348	T	C	0.279	188	239	0.787	6.091	0.0136	0.0224	0.8729
*NR1D1*	17	rs2314339	T	C	0.130	90	147	0.612	13.710	0.0002	0.0005	0.0338
*NR1D1*	17	rs2071427	A	G	0.256	191	256	0.746	9.452	0.0021	0.0019	0.2852
*NR1D1*	17	rs2269457	G	A	0.239	171	214	0.799	4.803	0.0284	0.0292	0.9861
*CSNK1D*	17	rs4510078	A	G	0.021	18	38	0.474	7.143	0.0075	0.0175	0.6942

GENE: NCBI gene symbol. CHR: chromosome number. SNP: dbSNP symbol. A1 & A2: minor and major allele nucleotides. MAF: minor allele frequency. T: number of transmissions of the rare allele. U: number of untransmitted rare alleles. OR: odds ratio of TDT. CHISQ: Chi Square from TDT. P: probability of Chi Square. EMP1: empirical probability from simulation by PLINK. EMP2: corrected empirical P (Max T/familywise).

Table 2

SNPs associated with the BALM among bipolar participants

Gene	CHR	SNP	A1	A2	MAF	BETA	R2	EMP1	EMP2	genotype freq
PER3	1	rs228697	G	C	0.083	-6.36	0.0913	0.0008	0.0150	4/15/110
CSNK1E	22	CSNK1E28266	A	G	0.025	13.67	0.0785	0.0008	0.0467	0/5/119
CSNK1E	22	CSNK1E27740	T	G	0.028	12.45	0.0753	0.0010	0.0506	0/6/121

CHR: chromosome. A1 & A2: minor and major allele nucleotides. MAF: minor allele frequency. R²: the correlation squared. EMP1: pointwise empirical P value. EMP2: corrected empirical P value from max/(T)/familywise.

Table 3

SNPs associated with unipolar recurrent major depression

Gene	CHR	SNP	A1	A2	MAF	OBS	EXP	EMP1	EMP2
PPARGC1B	5	rs7732671	C	G	0.092	14	10	0.0232	0.3148
TEF	22	rs738499	G	T	0.334	35	41.5	0.0114	0.2123

CHR: chromosome. A1 & A2: minor and major allele nucleotides. MAF: minor allele frequency. OBS: number of observed minor alleles. Exp: number of expected minor alleles. EMP1: pointwise empirical P value. EMP2: corrected empirical P value from max/(T)/familywise.

**Model relating sunlight, lithium, and circadian genes to MAOA and mania**. This model relates sunlight and lithium to components of the circadian gene system, to MAOA (monoamine oxidase A), dopamine, and resultant stimulation of mania. Green solid arrows represent interactions which promote the function of the affected component. Red striped arrows represent inhibition of the function of the affected component. Components in white boxes hypothetically promote mania. Components in black boxes hypothetically inhibit mania. The red-green striped box for PPARGC1B suggests its opposing roles in possibly stimulating both ARNTL and NR1D1, whereas NR1D1 then inhibits ARNTL. The positive feedback of ARNTL-CLOCK and ARNTL-NPAS2 heterodimers on NR1D1, TEF, PER1, PER2, and PER3 was omitted from the diagram for simplicity, along with many other components and interactions within the circadian system.

Circadian polymorphisms associated with affective disorders

Figures & Tables

Table 1

Table 2

Table 3

Figure 1

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