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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Basic Info

Reference	Dmitrzak-Weglarz, M. P., 2014 PMID: 25258123
Citation	Dmitrzak-Weglarz, M. P., et al. (2014). "Clock gene variants differentiate mood disorders." Mol Biol Rep.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	744 inpatients (393 BPDI, 122 BPDII and 229 UPD) and 635 healthy subjects
SNP/Region/Marker Size	42 SNPs
Predominant Ethnicity	Caucasian
Population	Polish
Gender	cases: 472 female and 272 male; controls: 326 female and 309 male
Age Group	adult : cases: mean=45, SD=14; controls: mean=39, SD=13

Detail Info

Sample Diagnosis	DSM-IV
Sample Status	The lifetime diagnosis was established using SCID-I (Structured Clinical Interview for Axis I clinical disorders for DSM-IV). Decreased need for sleep was found in 456 patients, while somnolence appeared for 174 patients. Among all patients 510 had a difficulty in falling asleep, 481 wake up at night and 508 patients declared wake up early. Recruited patients were treated in: the Department of Psychiatry, University of Medical Sciences in Poznan, in the Department of Psychiatry, University School of Medicine in Bydgoszcz and in the Psychiatric Hospital in Koscian.
Technique	Genotyped using TaqMan SNP Genotyping assays (Applied Biosystems) and TaqMan Genotyping Master Mix
Statistical Method	The statistical analyses were performed with licensed statistical package STATISTICA v. 10.0, and packages such as Haploview v. 4.2, and QUANTO v. 1.2.4 as well as R statistical software environment and appropriate package SNPassoc where necessary. Nonparametric Evaluation of Quantitative and Qualitative Traits in Population-Based Association Studies with the Log-Additive Genetic Model for complex disease was used.
Result Summary	We observed association between two polymorphisms of CLOCK (rs1801260 and rs11932595) with BPDII and two polymorphisms of TIM (rs2291739, rs11171856) with UPD. We also detected ARNTLhaplotype variant (rs1160996C/rs11022779G/rs1122780T) to be associated with increased risk of MD, BPD (both types). We established significant epistatic interaction between PER3 (rs2172563) and ARNTL (rs4146388 and rs7107287) in case of BPD. Additionally relation between PER3 (rs2172563) and CLOCK (rs1268271 and rs3805148) appeared in case of UPD. Classification and Regression Trees (C and RT) showed significant predictive value for 10 polymorphisms in all analyzed genes. However we failed to obtain model with sufficient predictive power. During analyses of sleep disturbances sample, we found carriers of homozygote variants (ARNTL: rs11022778 TT, rs1562438 TT, rs1982350 AA and PER3: rs836755 CC) showing more frequent falling asleep difficulties when compare to other genotypes carriers

SNPs reported by this study for BD (count: 10)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs11022780	ARNTL	T/C		MD (BPD and UPD): P-value=0.0211, FDR=0.2215, OR=0.83, 95%CI=0.71-0.97; BPD: P-value=0.0082, FDR=0.1200, OR=0.80, 95%CI=0.67-0.94; BPDI: P-value=0.0461, FDR=0.4600, OR=0.83, 95%CI=0.69-1.00; BPDII: P-value=0.0112, FDR=0.1051, OR=0.69, 95%CI=0.51-0.92.	Significant association was observed. Significant association was observed.	Positive
rs3816360	ARNTL	G/A		BPDII: P-value=0.0494, FDR=0.1888, OR=0.74, 95%CI=0.54-1.00.	Significant association was observed. Significant association was observed.	Positive
rs7947951	ARNTL	G/A		BPD: P-value=0.0499, FDR=0.3253, OR=0.84, 95%CI=0.7-1.00.	Significant association was observed. Significant association was observed.	Positive
rs11600996	ARNTL	T/C		MD (BPD and UPD): P-value=0.0071, FDR=0.1492, OR=0.81, 95%CI=0.69-0.94; BPD: P-value=0.0028, FDR=0.0636, OR=0.77, 95%CI=0.65-0.92; BPDI: P-value=0.0193, FDR=0.4056, OR=0.80, 95%CI=0.67-0.97; BPDII: P-value=0.0070, FDR=0.1035, OR=0.67, 95%CI=0.50-0.90.	Significant predictive value was observed. Significant predictive value was observed.	Positive
rs3789327	ARNTL	T/C		BPDII: P-value= 0.0405, FDR=0.1698, OR=0.74, 95%CI=0.56-0.99.	Significant association was observed. Significant association was observed.	Positive
rs2291739	TIMELESS ARHGEF5	T/C		MD (BPD and UPD): P-value=0.0451, FDR=0.3053, OR=1.19, 95%CI=1.00-1.40.	Polymorphisms rs2291739 of TIM gene was associated with MD r...... Polymorphisms rs2291739 of TIM gene was associated with MD risk. More...	Positive
rs11171856	TIMELESS MIP ARHGEF5	C/T		MD (BPD and UPD): P-value=0.0089, FDR=0.1492, OR=1.23, 95%CI=1.05-1.44; BPDII: P-value=0.0074, FDR=0.1035, OR=1.48, 95%CI=1.11-1.98.	SNPs rs11171856 of TIM gene was associated with BPDII risk. SNPs rs11171856 of TIM gene was associated with BPDII risk.	Positive
rs11932595	CLOCK TMEM165	A/G		BPDII: P-value=0.0319, FDR=0.1642, OR=1.37, 95%CI=1.03-1.84.	SNPs rs11932595 of CLOCK gene was associated with BPDII risk...... SNPs rs11932595 of CLOCK gene was associated with BPDII risk. More...	Positive
rs12648271	CLOCK	G/C		BPD: P-value=0.0353, FDR=0.3253, OR=0.82, 95%CI=0.68-0.99; BPDII: P-value=0.0311, FDR=0.1642, OR=0.71, 95%CI=0.51-0.98.	Significant association was observed. Significant association was observed.	Positive
rs1801260	CLOCK TMEM165	T/C		BPDII: P-value=0.0138, FDR=0.1051, OR=1.45, 95%CI=1.08-1.95.	SNPs rs1801260 of CLOCK gene was associated with BPDII risk. SNPs rs1801260 of CLOCK gene was associated with BPDII risk.	Positive

Haplotypes reported by this study for BD (count: 13)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs11824092 - rs1982350	C-A	ARNTL	BD: Case frequency=0.008, control frequency=0.015; Chi square=1.322, P-value=0.250	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs534654' target=_blank>rs534654 - rs534654' target=_blank>rs534654 - rs3805148	G-G-A	CLOCK	BD II: Case frequency=0.396, control frequency=0.308; Chi square=7.225, P-value=0.007	Significant association between this block and BD was observ...... Significant association between this block and BD was observed. More...	Positive
rs11600996 - rs11022779 - rs11022780	C-G-T	ARNTL	BD: Case frequency=0.606, control frequency=0.534; Chi square=6.087, P-value=0.013. BD I: Case frequency=0.596, control frequency=0.543; Chi square=5.432, P-value=0.0198. BD II: Case frequency=0.633, control frequency=0.543; Chi square=6.463, P-value=0.011	Significant association between this block and BD was observ...... Significant association between this block and BD was observed. More...	Positive
rs534654' target=_blank>rs534654 - rs534654' target=_blank>rs534654 - rs3805148	G-A-A	CLOCK	BD II: Case frequency=0.156, control frequency=0.169; Chi square=0.269, P-value=0.604	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs11600996 - rs11022779 - rs11022780	T-G-C	ARNTL	BD: Case frequency=0.226, control frequency=0.289; Chi square=5.935, P-value=0.014. BD I: Case frequency=0.233, control frequency=0.270; Chi square=3.369, P-value=0.0664. BD II: Case frequency=0.206, control frequency=0.270; Chi square=4.235, P-value=0.0396	We also found out ARNTL gene TGC haplotype of the (P-value=0...... We also found out ARNTL gene TGC haplotype of the (P-value=0.014) potentially protective against BPD. More...	Positive
rs534654' target=_blank>rs534654 - rs534654' target=_blank>rs534654 - rs3805148	A-A-A	CLOCK	BD II: Case frequency=0.112, control frequency=0.154; Chi square=2.819, P-value=0.093	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs11600996 - rs11022779 - rs11022780	T-A-C	ARNTL	BD: Case frequency=0.166, control frequency=0.171; Chi square=0.043, P-value=0.836. BD I: Case frequency=0.169, control frequency=0.181; Chi square=0.476, P-value=0.4902. BD II: Case frequency=0.157, control frequency=0.181; Chi square=0.809, P-value=0.3685	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs3789327 - rs11022778	A-T	ARNTL	BD II: Case frequency=0.626, control frequency=0.555; Chi square=4.095, P-value=0.043	Significant association between this block and BD was observ...... Significant association between this block and BD was observed. More...	Positive
rs3789327 - rs11022778	G-G	ARNTL	BD II: Case frequency=0.269, control frequency=0.289; Chi square=0.413, P-value=0.520	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs11824092 - rs1982350	C-G	ARNTL	BD: Case frequency=0.625, control frequency=0.561; Chi square=4.787, P-value=0.028	Significant association between this block and BD was observ...... Significant association between this block and BD was observed. More...	Positive
rs3789327 - rs11022778	G-T	ARNTL	BD II: Case frequency=0.105, control frequency=0.155; Chi square=4.037, P-value=0.044	Significant association between this block and BD was observ...... Significant association between this block and BD was observed. More...	Positive
rs11824092 - rs1982350	T-A	ARNTL	BD: Case frequency=0.363, control frequency=0.415; Chi square=3.24, P-value=0.071	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative
rs534654' target=_blank>rs534654 - rs534654' target=_blank>rs534654 - rs3805148	G-A-C	CLOCK	BD II: Case frequency=0.336, control frequency=0.369; Chi square=0.941, P-value=0.332	No significant association between this block and BD was obs...... No significant association between this block and BD was observed. More...	Negative

Genes reported by this study for BD (count: 4)

Gene	Statistical Values/Author Comments	Result Category
ARHGEF5	We found significant association between one TIM SNP and both BPDII and UPD. We found significant association between one TIM SNP and both BPDII and UPD.	Positive
CLOCK	We found significant association between two CLOCK SNPs (rs1801260 and rs11932595) and BPDII. We found significant association between two CLOCK SNPs (rs1801260 and rs11932595) and BPDII.	Positive
PER3	We established significant epistatic interaction between PER3 (rs2172563) and ARNTL(rs4146388 and rs...... We established significant epistatic interaction between PER3 (rs2172563) and ARNTL(rs4146388 and rs7107287) in case of BPD. More...	Positive
ARNTL	We detected ARNTL haplotype variant (rs1160996C/rs11022779G/rs1122780T) to be associated with increa...... We detected ARNTL haplotype variant (rs1160996C/rs11022779G/rs1122780T) to be associated with increased risk of MD, BPD (both types). More...	Positive

Gene-gene interactions reported by this study for BD (count: 2)

Gene Group	Markers	Statistical Values	Author Comments	Result Category
PER3 ARNTL	rs2172563 - rs4146388; rs2172563 - rs7107287	P-value<0.01	Significant SNPs pair interactions with P-value<0.01 in BD (...... Significant SNPs pair interactions with P-value<0.01 in BD (BD I and BD II). More...	Positive
PER3 CLOCK	rs10462021 - rs6849474; rs10462021 - rs12649507	P-value<0.01	Significant SNPs pair interactions with P-value<0.01 in BD (...... Significant SNPs pair interactions with P-value<0.01 in BD (BD I but not BD II). More...	Positive