Gene Report

Basic Info
Approved Symbol COMT
Approved Name catechol-O-methyltransferase
Location 22q11.21
Position chr22:19941607-19969975, 1
External Links HGNC: 2228
Entrez Gene: 1312
Ensembl: ENSG00000093010
UCSC: uc002zqu.3
No. of Studies 28 (Positive: 14; Negative: 14; trend: 0)
Overlap with SZ? YES
Overlap with MDD? YES
Gene related studies (count: 28)
Reference Tested Markers Statistical Values/Author Comments Result Category Comment on Study
Lachman, H. M., 1997 These data suggest that COMT is not a significant susceptibility gene in BPD occuring in the general population, in contrast with VCFS patient. Negative Comment on Study
Hukic, D. S.,2013 SNP: rs5993883, rs165599 Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population. Positive Comment on Study
Mynett-Johnson, L. A., 1998 Other variant: COMT_H/L Tests comparing transmitted and non-transmitted alleles provide no evidence that the polymorphism contributes to a susceptibility to bipolar disorder within the sample as a whole. However, amongst female bipolar I probands (n = 30) there was a tendency for the low-activity allele of COMT to be preferentially transmitted. Furthermore, a re-examination of an Irish case-control sample resulted in a similar observation amongst female bipolar I sufferers and pooling the data sets strengthened the findings. Positive Comment on Study
Pandolfo, G., 2015 Other variant: COMT_G1947A, COMT_C1886G This work first showed the association of combined Leu136Leu and Val158Met variants of COMT gene with MDD and BD. Positive Comment on Study
Li, T., 1997 Other variant: COMT_Val158Met, COMT_Codon108/158 We hypothesize that either the low activity allele of catechol-O-methyltransferase is a risk factor for bipolar affective disorder in Chinese populations or is in linkage disequilibrium with a nearby susceptibility gene or polymorphism. Positive Comment on Study
Wang, L. J., 2015 Other variant: COMT_Val158Met Our findings support preliminary evidence that the COMT and MTHFR genes interact in BP-II, and they imply the connection of both dopaminergic pathways and methylation pathways in the pathogenesis of BP-II. Logistic regression analysis showed a significant interaction effect of the COMT Val158Met Val/Val genotype and the MTHFR C677T C/T + T/T genotype for the protective effect on the odds of developing BP-II. Positive Comment on Study
Lee, H. Y.,2010 Other variant: COMT_Val158Met No statistically significant difference in genotype distribution was found between manic patients and normal controls. Negative Comment on Study
Massat, I.,2011 SNP: rs165599, rs2075507, rs4633, rs4680, rs4818, rs6269, rs737865 In conclusion, we partially replicated our previous findings confirming a possible influence of COMT variants in MD and BD, particularly in early onset subjects, though not with the same risk genotypes. Positive Comment on Study
Kirov, G.,1999(a) Other variant: COMT_Val158Met No statistically significant differences were found between transmitted and not transmitted alleles for any of the polymorphisms studied. Negative Comment on Study
Rotondo, A.,2002 Other variant: COMT_Val158Met The findings support the hypothesis that comorbid panic disorder identifies a genetic subtype of bipolar disorder and suggest a role for COMT and 5-HTT in vulnerability to these disorders. Positive Comment on Study
Gutierrez, B.,1997(b) Other variant: COMT_Val158Met, COMT_C256G No allelic or genotypic associations were observed.The lack of association suggests that the COMT gene is not a major risk factor for bipolar disorder. Negative Comment on Study
Biomed European Bipolar Collaborative Group,1997 Other variant: COMT_Val158Met We found no evidence of allelic or genotypic association.We can conclude that variation at this functional polymorphism does not make an important contribution to bipolar disorder in the Western European population. Negative Comment on Study
Lee, S. Y.,2012(b) Other variant: COMT_Val158Met Our findings provide initial evidence that the COMT and BDNF genes interact in bipolar-II without AD. Our findings suggest the involvement of dopaminergic pathway in the pathogenesis of bipolar-II. Positive Comment on Study
Kunugi, H.,1997(b) Other variant: COMT_Val158Met We conclude that genetic variation that determines high and low activities of COMT does not have a major effect on the vulnerability to affective disorders in our sample. Negative Comment on Study
Dickerson, F. B., 2006 Other variant: COMT_Val158Met COMT Val158Met polymorphism is not associated with bipolar disorder, but affects cognitive functioning in individuals with bipolar disorder. Negative Comment on Study
Burdick, K. E., 2007 SNP: rs165599, rs737865
Other variant: COMT_Val158Met, COMT_P2 promoter_-278A/G
A significant association between a single SNP in the COMT gene (rs165599) and BPD I was reported Positive Comment on Study
Serretti, A., 2006 Other variant: COMT_G/A COMT variants were not a major liability factor for mood disorder and for mood disorder symptomatology in the present sample Positive Comment on Study
Prata, D. P., 2006 SNP: rs165599, rs4680, rs737865 Our work does not support an involvement of RGS4, PRODH, COMTand GRK3 genes in the aetiology of bipolar affective disorder 1 in the Scottish population. Negative Comment on Study
Shifman, S., 2004 SNP: rs165599, rs4680, rs737865
Haplotype: rs737865 - rs165599(G-G), rs737865 - rs165688 - rs165599(G-G-G)
the current association between COMT and bipolar disorder is relatively modest Positive Comment on Study
Van Den Bogaert, A., 2006 (b) Other variant: COMT_Val158Met Together, our data suggest that these functional variants are not involved in the etiology of bipolar disorder in the northern Swedish population nor did gene-gene interaction analysis support a central role of these variants in bipolar disorder.. Negative Comment on Study
Ohara, K., 1998 Other variant: COMT_H/L Our results did not suggest the COMTL allele contributed to the etiologies of bipolar disorders. Negative Comment on Study
Kirov, G., 1998 Other variant: COMT_NlaIII Our data support the hypothesis that variation in the COMT gene modifies the course of bipolar disorder. Positive Comment on Study
Mick, E.,2009 Other variant: COMT_Val158Met Our study suggests that markers examined thus far in COMT are not associated with pediatric bipolar disorder. Negative Comment on Study
Zhang, Z.,2009(b) SNP: rs4680 In conclusion, the low-activity allele (Met) of rs4680 in COMT gene possibly confers risk for bipolar disorder in the Han population, while it needs further evidence for concluding its association with BP in the Caucasian population. Positive Comment on Study
Fallin, M. D.,2005 7 SNP typed, Median D'=0.87, Median r<sup>2</sup> =0.36, 3 LD blocks, 0.73 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
Funke, B.,2005 SNP: rs165599, rs2097063, rs4680, rs737865 Our results support the view that COMT variation provides a weak general predisposition to neuropsychiatric disease including psychotic and affective disorders.One variation Val158Met showed a trend towards association in the group of bipolar patients. Negative Comment on Study
Massat, I.,2005 Other variant: COMT_Val158Met Results did not show any significant difference when comparing the distribution of genotypes and alleles between BPD patients, EO-BPD patients and control subjects. Negative Comment on Study
Ancin, I.,2011(b) SNP: rs165599, rs2075507, rs4680
Haplotype: rs2075507 - rs4680 - rs165599(A-A-G)
Our results support the association of the COMT gene with BD and with one of its potential endophenotypes, auditory sensory gating deficit, measured by the P50 paradigm. Positive Comment on Study
Gene functional annotation
Gene related GO terms (count: 37)

GO terms by PBA (count: 6)

GO terms by database search (count: 31)

Gene related KEGG pathways (count: 1)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 1)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 4)

Related other genetic factors
Gene related SNPs (count: 18)

Literature-origin SNPs (count: 9)

LD-proxies (count: 9)

Gene related CNVs (count: 1)

Gene related other variants (count: 9)

Gene related regions (count: 3)

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

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

Overlap with SZ from candidate gene intersection analysis (count: 85)

Gene relationship with MDD

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

Overlap with MDD from candidate gene intersection analysis (count: 3)

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Region: chr22:19941607..19969975 View in gBrowse
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