SNP Report

Basic Info

Name	rs1006737 dbSNP Ensembl
Location	chr12:2236129 - 2236129(1)
Variant Alleles	G/A
Ancestral Allele	G
Minor Allele	A
Minor Allele Frequence	0.301518
Functional Annotation	intron_variant.
Consequence to Transcript	intron_variant(ENST00000327702, ENST00000335762, ENST00000344100, ENST00000347598, ENST00000399591, ENST00000399595, ENST00000399597, ENST00000399601, ENST00000399603, ENST00000399606, ENST00000399617, ENST00000399621, ENST00000399629, ENST00000399634, ENST00000399637, ENST00000399638, ENST00000399641, ENST00000399644, ENST00000399649, ENST00000399655, ENST00000402845, ENST00000406454, ENST00000480911, LRG_334t1, LRG_334t2, LRG_334t3, LRG_334t4)
No. of Studies	15 (Positive: 9; Negative: 4; Trend: 2)
Source	Literature
Overlap with SZ?	YES
Overlap with MDD?	YES

SNP related studies (count: 15)

Reference	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
Jogia, J.,2011	A/G	A	bipolar disorder (BD) patients vs. their unaffected relative...... bipolar disorder (BD) patients vs. their unaffected relatives and controls in the right vlPFC (x=54 y=36 z = 12 z-score = 3.64), P-value < 0.05 More...	The present findings suggest that the CACNA1C rs1006737 poly...... The present findings suggest that the CACNA1C rs1006737 polymorphism impacts on vlPFC activation during fear processing in BD carriers of the risk allele but not their unaffected relatives. More...	Positive
Jan, W. C., 2014	G/A		HWE; OR=0.5, 95%CI=0.05-5.59, P-value=0.58 for BD-I; OR=1.79...... HWE; OR=0.5, 95%CI=0.05-5.59, P-value=0.58 for BD-I; OR=1.79, 95%CI=0.7-4.17, P-value=0.18 for BD-II. More...	Results of single marker association tests. Results of single marker association tests.	Negative
Perrier, E.,2011	A/G	A	Genotype by diagnosis interaction : patients with the risk a...... Genotype by diagnosis interaction : patients with the risk allele vs. controls: the left putamen was smaller(F3, 87=4.612, p =0.035) More...	Significant association was found . Significant association was found .	Positive
Ferreira, M. A.,2008		A	Genotyped P value=7E-08, OR=1.181 in the combined analysis o...... Genotyped P value=7E-08, OR=1.181 in the combined analysis of WTCCC, STEP-UCL and ED-DUB-STEP2 datasets. Genotyped P value=0.0015 in the WTCCC. Genotyped P value=0.0003 in the STEP-UCL. Genotyped P value=0.0108 in the ED-DUB-STEP2 dataset. More...		Positive
Andreassen OA, 2013	A/G		Conditional FDR; SCZ loci given BD: FDR=0.022 for SCZ and BD...... Conditional FDR; SCZ loci given BD: FDR=0.022 for SCZ and BD\|\|Conjunction FDR; pleiotropic loci in SCZ and BD: FDR=0.022 for BD and SZ, Z-score=4.553 for BD More...	To estimate the number of independent loci, we 'pruned' the ...... To estimate the number of independent loci, we 'pruned' the associated SNPs (removed SNPs with linkage disequilibrium (LD)>0.2), and identified a total of 58 independent loci with a significance threshold of conditional FDR<0.61. This SNP is with conjunction FDR<0.13 with schizophrenia and bipolar disorder considered jointly. More...	Positive
Uemura, T., 2015			genotypic P-value=0.89, X²=0.24 for BD-II patient...... genotypic P-value=0.89, X²=0.24 for BD-II patients, P-value=0.035, X²²=0.29, OR (95%CI)=1.15 (0.69-1.93) for BD-II patients, P-value=0.15, X²=2.11, OR (95%CI)=1.38 (0.89-2.13) for BD-I patients More...	no significant differences were observed in the genotype fre...... no significant differences were observed in the genotype frequencies compared with healthy subjects among BD-II patients. CACNA1C SN P rs1006737 was significantly associated with BD-I in genotype frequency. However, allele frequencies were not significantly different in BD-I, BD-II compared with healthy subjects. More...	Positive
Gonzalez, S.,2013	G/A		Family-Based Association: allele G,frequency is 0.712,100 fa...... Family-Based Association: allele G,frequency is 0.712,100 families,Z = -0.725,P-value = 0.469 More...	No significant association was observed. No significant association was observed.	Negative
Tesli, M.,2013	A/G		BP: left amygdala (x = -24, y = 0, z =-14; Z = 3.35; cluster...... BP: left amygdala (x = -24, y = 0, z =-14; Z = 3.35; cluster-size = 91 , FWE-corrected P= 0.041). More...	The risk allele was significantly associated with enhanced a...... The risk allele was significantly associated with enhanced activity in the left amygdala (x =224, y = 0, z=214; Z = 3.35; cluster-size = 91) in the BD group (FWE-corrected P= 0.041). More...	Positive
Soeiro-de-Souza, M. G.,2013(b)	A/G		In the BD group database, results revealed that CACNA1C Met/...... In the BD group database, results revealed that CACNA1C Met/Met genotype compared with Val/Val genotype had worse cognitive performance in: WAI-SDS-FW (B = -1.9 P = 0.03 Partial Î·2 4.3% power 57.6%), WCSTCONC(B = -7.9 P = 0.01 Partial Î·2 6.3% power 74.2%), WCST-PR (B = 6.6 P = 0.01 Partial Î·2 5.8% power 70.8%), WCST-E (B = 8.1 P = 0.008 Partial Î·2 6.6% power 76.9%), WCST-P (B = 4.4 P = 0.02 Partial Î·2 5.1% power 65.1%), WAISBD(B = -11.0 P = 0.007 Partial Î·2 6.8% power 77.7%), WAIS-MR (B = -6.1 P = 0.02 Partial Î·2 4.6% power 59%), IQ (B = -9.2 P = 0.02 Partial Î·2 5% power 64.3%), TMT-A (B = 16.7 P = 0.004 Partial Î·2 7.8% power 83.4%) (Table 2). Val/Met genotype performed worse than Val/Val genotype only on TMT-A (B = 8.3 P = 0.01 Partial Î·2 6.1% power 73.1%) and TMT-B (B = 19.0 P = 0.008 Partial Î·2 6.7% power 77%). In the control group, the same MANOVA model revealed no influence of CACNA1C genotype on cognitive performance. More...	In patients with BD, the CACNA1C genotype Met/Met was associ...... In patients with BD, the CACNA1C genotype Met/Met was associated with worse performance on all four executive function tests compared to Val/Val. No influence of CACNA1C was observed in the cognitive performance of healthy controls. More...	Positive
Green, E. K., 2010		A	P=7.0E-7 reported in a meta-analysis of three genome-wide as...... P=7.0E-7 reported in a meta-analysis of three genome-wide association studies of BD. More...	strong significance strong significance	Positive
Ruderfer, D. M., 2013			P-value=7.43E-08 for BP, P-value=5.53E-13 for BP+SZ, Het P-v...... P-value=7.43E-08 for BP, P-value=5.53E-13 for BP+SZ, Het P-value=0.85 More...	The most significant SNP, rs1006737, falls within the gene C...... The most significant SNP, rs1006737, falls within the gene CACNA1C that was first found to be significant in BP, subsequently in SCZ. In our independent disease samples, we find similar ORs for both disorders (BP OR=1.127; SCZ OR=1.120). More...	Positive
Liu, Y.,2011			Meta analysis: P-value = 7.0E-08 Meta analysis: P-value = 7.0E-08	Suggestive association was found. Suggestive association was found.	Trend
Soeiro-de-Souza, M. G.,2012			chi square test:P-value = 0.38 chi square test:P-value = 0.38	CACNA1C genotype frequency was similar in both groups. CACNA1C genotype frequency was similar in both groups.	Negative
Lett, T. A.,2011	G/A	A	FBAT: P-value = 0.077 FBAT: P-value = 0.077	No significant association was observed in BD. No significant association was observed in BD.	Negative
Green, E. K.,2012	A/G		BD ImmunoChip:P-value = 0.000409,OR = 1.198;ImmunoChip, PGC-...... BD ImmunoChip:P-value = 0.000409,OR = 1.198;ImmunoChip, PGC-BD combined data:P-balue = 0.000000216,OR = 1.128 More...	Suggestive association was found. Suggestive association was found.	Trend

SNP related genes (count: 1)

Approved Symbol	Approved Name	Location	No. of Studies (Positive/Negative/Trend)
CACNA1C	calcium channel, voltage-dependent, L type, alpha 1C subunit	12p13.3	20(17/3/0)

SNPs in LD with rs1006737 (count: 8) View in gBrowse (chr12:2223629..2299028 )

The LD data used here is based on HapMap rel#27. LD SNP pairs were selected with a threshold r²<=0.8.

Literature-origin SNPs (count: 0)

LD-proxies (count: 8)

rs_ID	Functional Annotation	r²[population]
rs1108221	intron_variant; upstream_gene_variant	1.0[CHB]
rs12315711	intron_variant	1.0[CEU]; 1.0[CHB]; 1.0[JPT]
rs10774035	intron_variant	1.0[CEU]; 1.0[TSI]; 0.823[CHB]; 1.0[JPT]
rs10774036	intron_variant; non_coding_transcript_variant	0.958[CEU]; 1.0[JPT]
rs2007044	intron_variant	0.809[CEU]; 0.804[TSI]
rs4298967	intron_variant	0.918[CEU]; 0.908[TSI]
rs10744560	intron_variant; non_coding_transcript_variant	0.958[CEU]; 0.937[TSI]; 1.0[JPT]
rs11062170	intron_variant	1.0[CEU]; 1.0[CHB]; 1.0[JPT]

Overlap with SZ from cross-disorder studies (count: 4)

Reference	Statistical Result	Description	Result Category
Andreassen OA, 2013	Conditional FDR; SCZ loci given BD: P-value=0.0000352, FDR=0.104, FDR=0.022 for SCZ and BD\|\|Conjunction FDR; pleiotropic loci in SCZ and BD: FDR=0.022 for BD and SZ, Z-score=4.137 for SZ	To estimate the number of independent loci, we 'pruned' the associated SNPs (removed SNPs with linkage disequilibrium (LD)>0.2), and identified a total of 58 independent loci with a significance threshold of conditional FDR<0.61. This SNP is with conjunction FDR<0.13 with schizophrenia and bipolar disorder considered jointly.	Positive
Green, E. K., 2010	genotype test P-value = 0.034 when using Controls (WTCCC) as control, genotype test P-value = 0.043 when using WTCCC expanded reference as control, OR(%95 CI) =1.15 (0.99-1.32) for allele test when using Controls (WTCCC) as control, OR(%95 CI)=1.13 (0.98-1.29) for allele test when using WTCCC expanded reference as control;	We found that the risk allele conferred increased risk for schizophrenia (P= 0.034) with similar effect sizes to those previously observed in BD (allelic odds ratio B1.15).	Positive
Ruderfer, D. M., 2013	P-value=1.65E-06 for BP, P-value=5.53E-13 for BP+SZ, Het P-value=0.85	The most significant SNP, rs1006737, falls within the gene CACNA1C that was first found to be significant in BP, subsequently in SCZ. In our independent disease samples, we find similar ORs for both disorders (BP OR=1.127; SCZ OR=1.120).	Negative
Tesli, M.,2013	SZ: right amygdala (x = 24, y = -4, z =-16; Z = 2.24; cluster-size = 26 , FWE-corrected P= 0.449).	There were no FWE-corrected significant findings in SZ individuals or healthy controls.	Negative

Overlap with MDD from cross-disorder studies (count: 3)

Reference	Statistical Result	Description	Result Category
Green, E. K., 2010	genotype test P-value = 0.013 when using New controls as control, genotype test P-value = 3.9E-4 when using WTCCC expanded reference as control, OR(%95 CI) = 1.15 (1.02-1.31) for allele test when using New controls as control, OR(%95 CI) = 1.17 (1.07-1.27) for allele test when using WTCCC expanded reference as control.	We found that the risk allele conferred increased risk for recurrent major depression (P= 0.013) with similar effect sizes to those previously observed in BD (allelic odds ratio B1.15).	Positive
Liu, Y.,2011	Meta analysis:P-value = 3.1E-08	Suggestive association was found.	Trend
Uemura, T., 2015	genotypic P-value=0.33, X²=2.23; allelic P-value=0.39, X²=0.75, OR (95%CI)=0.73 (0.36-1.48)	no significant differences were observed in the genotype frequencies compared with healthy subjects among MDD patients. However, allele frequencies were not significantly different in MDD compared with healthy subjects.	Negative