Gene Report

Basic Info
Approved Symbol DISC1
Approved Name disrupted in schizophrenia 1
Location 1q42.1
Position chr1:231626815-232041272, 1
External Links HGNC: 2888
Entrez Gene: 27185
Ensembl: ENSG00000162946
UCSC: uc010pxh.2
No. of Studies 18 (Positive: 10; Negative: 7; trend: 1)
Overlap with SZ? YES
Overlap with MDD? YES
Gene related studies (count: 18)
Reference Tested Markers Statistical Values/Author Comments Result Category Comment on Study
Palo, O. M., 2007 SNP: rs1000731, rs1322784, rs1411771, rs1538977, rs3738401, rs6675281, rs751229, rs821616, rs967244, rs980989
Haplotype: rs1000731 - rs821616(C-T), rs1000731 - rs821616 - rs1411771(C-T-T), rs1322784 - rs967244(A-G), rs1411771 - rs980989(T-G), rs1538977 - rs1322784(A-A), rs3738401 - rs1538977(A-A), rs6675281 - rs1000731(T-C), rs6675281 - rs1000731 - rs821616(T-C-T), rs751229 - rs3738401(T-A), rs821616 - rs1411771(T-T), rs821616 - rs1411771 - rs980989(T-T-G), rs967244 - rs6675281(G-T), rs1615409 - rs1655285 - rs751229(C-G-T), rs1655285 - rs751229(G-T), rs1655285 - rs751229 - rs3738401(G-T-A)
The results provide evidence for an association of distinct allelic variants of DISC1 to psychotic and bipolar spectrum disorders. Positive Comment on Study
Maeda, K., 2006 SNP: rs1000731, rs1407598, rs1538975, rs1954175, rs2273890, rs3524, rs3737597, rs3738401, rs6675281, rs821616, rs821653
Haplotype: rs1538975 - rs3738401 - DISC1_Exon2_Pro/Leu - rs1954175 - rs2273890 - rs1407598 - rs6675281 - rs1000731 - rs821653 - rs821616 - rs3524 - rs3737597(G-G-C-A-T-A-C-G-T-A-C-G), rs1538975 - rs3738401 - DISC1_Exon2_Pro/Leu - rs1954175 - rs2273890 - rs1407598 - rs6675281 - rs1000731 - rs821653 - rs821616 - rs3524 - rs3737597(G-G-C-A-T-C-C-A-T-A-C-G)
Other variant: DISC1_exon2_Pro/Leu
These results suggest that decreased mRNA levels of DISC1 expression, associating with the risk haplotype, may be implicated in the pathophysiology of bipolar disorder. Positive Comment on Study
Ram Murthy, A., 2012 SNP: rs2812393, rs3738401, rs821616
Haplotype: rs766288 - rs3738401 - rs2812393 - rs821616(C-G-G-T), rs766288 - rs3738401 - rs2812393 - rs821616(A-G-G-T), rs766288 - rs821616(C-A), rs766288 - rs821616(A-A), rs766288 - rs821616(C-T), rs766288 - rs821616(A-T), rs766288 - rs2812393(C-C), rs766288 - rs2812393(A-G), rs766288 - rs2812393(C-G ), rs766288 - rs2812393(A-C ), rs2812393 - rs821616(C-A), rs2812393 - rs821616(G-A), rs2812393 - rs821616(G-T), rs2812393 - rs821616(C-T)
Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD. Positive Comment on Study
Perlis, 2008 SNP: rs1015101, rs10864702, rs11577215, rs1934909, rs2759346 permuted P< .005 in gene-based association tests. Among 3 genes associated with schizophrenia or bipolar disorder in multiple previous studies, only DISC1 showed evidence of association in this cohort. hese results suggest novel candidates and 1 gene (DISC1) previously associated with schizophrenia that merit further study in bipolar disorder. Positive Comment on Study
Prata, D. P.,2011 SNP: rs821616 No significant associations were detected in BP patients. Negative Comment on Study
Xiao, Y.,2011 SNP: rs1417866, rs1538977, rs1572899, rs16841582, rs1954175, rs2038636, rs2738864, rs3524, rs734551, rs821597, rs821653
Haplotype: rs1572899 - rs1954175(A-C), rs2738864 - rs16841582(C-C), rs821597 - rs821653(A-A)
This finding provides evidence supporting the role of DISC1 gene in bipolar disorder, and shows the presence of population heterogeneity. Positive Comment on Study
Green, E. K.,2011 SNP: rs821616 The known non-synonymous polymorphism rs821616 (Ser704Cys) was not significantly associated with disease. Negative Comment on Study
Song, W.,2010 Other variant: DISC1_1013 G>A, DISC1_1253 G>A, DISC1_2261 C>G, DISC1_627 C>G, DISC1_IVS1+3 A>T, DISC1_1700 G>A, DISC1_2425 TCATdel, DISC1_74 G>A, DISC1_790 C>T, DISC1_887 A>G In our sample, ultra-rare(private) protein structural variants in DISC1 are associated with an estimated attributable risk of about 0.5% in bipolar spectrum disorder. Trend Comment on Study
Devon, R. S.,2001 Other variant: DISC1_A844G, DISC1_C1460T, DISC1_G65049, DISC1_T11840C, DISC1_T2163A Neither co-segregation with disease status nor significant association was detected. Negative Comment on Study
Hodgkinson, C. A.,2004 SNP: rs1407598, rs1535529, rs3524 These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders. Positive Comment on Study
McDonald, M. L.,2012 SNP: rs10495310, rs2812391, rs4658954 None of the association tests of the tagSNPs with either BPD I or BPD II reached genome-wide significance (P < 5E-08). Negative Comment on Study
Arai, M., 2007 SNP: rs3738398
Haplotype: rs3738398 - DISC1_-215(TG)8-13([G-(TG)<sub>8</sub>], [G-(TG)<sub>9</sub>], [C-(TG)<sub>12</sub>])
Other variant: DISC1_-215(TG)8-13
The polymorphisms in 5' upstream region of the DISC1 gene are unlikely to play a major role in the susceptibility to mood disorders in the Japanese population. Negative Comment on Study
Yosifova, A.,2009 SNP: rs1322784, rs1538977, rs2492367, rs2812393 No SNP of this gene had significant association with BD in our population. Negative Comment on Study
Schosser, A., 2010 SNP: rs1000731, rs12133766, rs2492367, rs3738401, rs6675281, rs7546310, rs821597
Haplotype: rs1000731 - rs7546310(AC), rs1000731 - rs7546310 - rs821597(ACC), rs12133766 - rs1000731(GA), rs12133766 - rs1000731 - rs7546310(GAC), rs2492367 - rs6675281(TC), rs2492367 - rs6675281 - rs12133766(TCG), rs6675281 - rs12133766 - rs1000731(CGA), rs7546310 - rs821597(AT), rs766288 - rs2492367 - rs6675281(ACC), rs766288 - rs2492367(AC)
We found a significant allelic and genotypic association of the TSNAX-DISC1 gene region with BD. Positive Comment on Study
Thomson, P. A.,2005(a) SNP: rs1000730, rs1000731, rs1025526, rs1030711, rs1094653, rs11122396, rs1160491, rs12404162, rs1322784, rs1411771, rs1411776, rs1538977, rs1615409, rs1630250, rs1954175, rs1984895, rs2038636, rs2492367, rs2759346, rs2812393, rs3738401, rs6675281, rs701158, rs734551, rs751229, rs766288, rs821597, rs821616, rs821663, rs999710
Haplotype: rs1538977 - rs2492367 - rs2812393(T-T-G), rs1538977 - rs2492367 - rs2812393 - rs1322784(T-T-G-T), rs1954175 - rs1538977 - rs2492367(), rs1954175 - rs1538977 - rs2492367 - rs2812393(A-C-C-G), rs1954175 - rs1538977 - rs2492367 - rs2812393(G-T-T-G), rs2492367 - rs2812393 - rs1322784(C-C-C), rs2492367 - rs2812393 - rs1322784(C-G-T), rs2492367 - rs2812393 - rs1322784 - rs2759346(), rs2812393 - rs1322784(C-C), rs2812393 - rs1322784 - rs2759346 - rs6675281()
This result provides further supporting evidence for DISC1 as a susceptibility factor for both bipolar disorder and schizophrenia, consistent with the diagnoses in the original Scottish translocation family. Positive Comment on Study
Fallin, M. D.,2005 19 SNP typed, Median D'=0.16, Median r<sup>2</sup> =0, 10 LD blocks, 0.46 block coverage, all SNP or haplotype P-value > 0.05 in BP and SZ/SZA... This gene is not suggestive to BP. Negative Comment on Study
Chakirova, G.,2011 SNP: rs1538979, rs821633 In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of bipolar disorder. Positive Comment on Study
Hennah, W.,2009 SNP: rs1538979, rs821577 These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts. Positive Comment on Study
Gene functional annotation
Gene related GO terms (count: 21)

GO terms by PBA (count: 1)

GO terms by database search (count: 20)

Gene related KEGG pathways (count: 0)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 18)

Related other genetic factors
Gene related SNPs (count: 245)

Literature-origin SNPs (count: 56)

LD-proxies (count: 189)

Gene related CNVs (count: 0)

Gene related other variants (count: 17)

Gene related regions (count: 2)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)
Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 7)

Overlap with SZ from candidate gene intersection analysis (count: 32)

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 2)

Overlap with MDD from candidate gene intersection analysis (count: 2)

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Region: chr1:231626815..232041272 View in gBrowse
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