NDLI: A Haplotype Implicated in Schizophrenia Susceptibility Is Associated with Reduced COMT Expression in Human Brain

Content Provider	PubMed Central
Author	Bray, Nicholas J. Buckland, Paul R. Williams, Nigel M. Williams, Hywel J. Norton, Nadine Owen, Michael J. O’donovan, Michael C.
Copyright Year	2003
Abstract	The gene encoding catechol-O-methyltransferase (COMT) is a strong candidate for schizophrenia susceptibility, owing to the role of COMT in dopamine metabolism, and the location of the gene within the deleted region in velocardiofacial syndrome, a disorder associated with high rates of schizophrenia. Recently, a highly significant association was reported between schizophrenia and a COMT haplotype in a large case-control sample (Shifman et al. 2002). In addition to a functional valine→methionine (Val/Met) polymorphism, this haplotype included two noncoding single-nucleotide polymorphisms (SNPs) at either end of the COMT gene. Given the role of COMT in dopamine catabolism and that deletion of 22q11 (containing COMT) is associated with schizophrenia, we postulated that the susceptibility COMT haplotype is associated with low COMT expression. To test this hypothesis, we have applied quantitative measures of allele-specific expression using mRNA from human brain. We demonstrate that COMT is subject to allelic differences in expression in human brain and that the COMT haplotype implicated in schizophrenia (Shifman et al. 2002) is associated with lower expression of COMT mRNA. We also show that the 3′ flanking region SNP that gave greatest evidence for association with schizophrenia in that study is transcribed in human brain and exhibits significant differences in allelic expression, with lower relative expression of the associated allele. Our results indicate that COMT variants other than the Val/Met change are of functional importance in human brain and that the haplotype implicated in schizophrenia susceptibility is likely to exert its effect, directly or indirectly, by down-regulating COMT expression.
Related Links	http://dx.doi.org/10.1086/376578
Ending Page	161
Page Count	10
Starting Page	152
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	1
Volume Number	73
Language	English
Publisher	The American Society of Human Genetics
Publisher Date	2003-07-01
Access Restriction	Open
Rights Holder	The American Society of Human Genetics
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain.

A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain

A Highly Significant Association between a COMT Haplotype and Schizophrenia

RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity

MAD1L1 and TSNARE gene polymorphisms are associated with schizophrenia susceptibility in the Han Chinese population

Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model

Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs

Genetic Susceptibility to Type 2 Diabetes Is Associated with Reduced Prostate Cancer Risk

A Polymorphism in Human CD1A is Associated with Susceptibility to Tuberculosis

A Haplotype Implicated in Schizophrenia Susceptibility Is Associated with Reduced COMT Expression in Human Brain

Similar Documents

A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain.

A functional haplotype implicated in vulnerability to develop cocaine dependence is associated with reduced PDYN expression in human brain

A Highly Significant Association between a COMT Haplotype and Schizophrenia

RGS4 mRNA expression in postmortem human cortex is associated with COMT Val158Met genotype and COMT enzyme activity

MAD1L1 and TSNARE gene polymorphisms are associated with schizophrenia susceptibility in the Han Chinese population

Serine racemase is associated with schizophrenia susceptibility in humans and in a mouse model

Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs

Genetic Susceptibility to Type 2 Diabetes Is Associated with Reduced Prostate Cancer Risk

A Polymorphism in Human CD1A is Associated with Susceptibility to Tuberculosis

A Haplotype Implicated in Schizophrenia Susceptibility Is Associated with Reduced COMT Expression in Human Brain